Journal Of Medicinal Chemistry Research Articles

Current perspectives and trend of computer-aided drug design: a review and bibliometric analysis.

Computer-aided drug design (CADD) is a drug design technique for computing ligand‒receptor interactions and is involved in various stages of drug development. To better grasp the frontiers and hotspots of CADD, we conducted a review analysis through bibliometrics. A systematic review of studies published between 2000 and July 20, 2023 was conducted following the PRISMA guidelines. Literature on CADD was selected from the Web of Science Core Collection. General information, publications, output trends, countries/regions, institutions, journals, keywords, and influential authors were visually analysed using software such as Excel, VOSviewer, RStudio, and CiteSpace. A total of 2,031 publications were included. These publications primarily originated from 99 countries or regions, led by the U.S. and China. Among the contributors, MacKerell AD had the highest number of articles and greatest influence. The Journal of Medicinal Chemistry was the most cited journal, whereas the Journal of Chemical Information and Modeling had the highest number of publications. Influential authors in the field were identified. Current research shows active collaboration between countries, institutions, and companies. CADD technologies such as homology modelling, pharmacophore modelling, quantitative conformational relationships, molecular docking, molecular dynamics simulation, binding free energy prediction, and high-throughput virtual screening can effectively improve the efficiency of new drug discovery. Artificial intelligence-assisted drug design and screening based on CADD represent key topics direction for future development. Furthermore, this paper will be helpful for better understanding the frontiers and hotspots of CADD.

An Analysis of Successful Hit-to-Clinical Candidate Pairs.

An analysis of 156 published clinical candidates from the Journal of Medicinal Chemistry between 2018 and 2021 was conducted to identify lead generation strategies most frequently employed leading to drug candidates. As in a previous publication, the most frequent lead generation strategies resulting in clinical candidates were from known compounds (59%) followed by random screening approaches (21%). The remainder of the approaches included directed screening, fragment screening, DNA-encoded library screening (DEL), and virtual screening. An analysis of similarity was also conducted based on Tanimoto-MCS and revealed most clinical candidates were distant from their original hits; however, most shared a key pharmacophore that translated from hit-to-clinical candidate. An examination of frequency of oxygen, nitrogen, fluorine, chlorine, and sulfur incorporation in clinical candidates was also conducted. The three most similar and least similar hit-to-clinical pairs from random screening were examined to provide perspective on changes that occur that lead to successful clinical candidates.

Scenes from the ACS Spring 2023 hybrid meeting in Indianapolis

ACS MEETINGS NEWS Scenes from the ACS Spring 2023 hybrid meeting in Indianapolis ShareShare onFacebookTwitterWechatLinked InRedditEmail Emily Abbott, ACS staffC&EN, 2023, 101 (12), pp 28–29April 10, 2023Cite this:C&EN 101, 12, 28-29Students from the University of Tennessee, Knoxville, take a break from the meeting with a fun game of Jenga in the student lounge. (Credit: Event Photography of North America Corporation)Figure1of11William F. Carroll Jr. (right), a former ACS president, celebrates receiving the Charles Lathrop Parsons Award with his wife, Mary Carroll (second from right), and other supporters. (Credit: Event Photography of North America Corporation)Figure1of11Cato T. Laurencin, the 2023 Priestley Medal winner, gives his address at the ACS National Awards ceremony. (Credit: Event Photography of North America Corporation)Figure2of11A panel event featured, from left: Chuan He, editor in chief of ACS Chemical Biology; Prashant V. Kamat, editor in chief of ACS Energy Letters; Christa E. Müller, editor in chief of ACS Pharmacology and Translational Science; Kenneth M. Merz Jr., editor in chief of the Journal of Chemical Information and Modeling; Craig Lindsley, editor in chief of the Journal of Medicinal Chemistry; and Gregory Hartland, deputy editor of the Journal of Physical Chemistry C. (Credit: Event Photography of North America Corporation)Figure3of11Meeting attendees check out a vendor in the ACS expo hall. (Credit: Event Photography of North America Corporation)Figure4of11From left: ACS Board chair Paul Jagodzinski, contestant Jianping Huang, host Mark Gindick, C&EN editor and contestant Manny I. Fox Morone, and C&EN reporter and contestant Ariana Remmel. A game of C&EN Jeopardy! celebrated—and tested contestants’ knowledge of—100 years of the magazine. (Credit: Event Photography of North America Corporation)Figure5of11ACS president Judith C. Giordan poses with Meg A. Mole at the ACS Kids Zone. (Credit: Christine Schmidt)Figure6of11From left: ACS president-elect Mary K. Carroll, president Judith C. Giordan, and immediate past president Angela K. Wilson at the ACS National Awards reception (Credit: Event Photography of North America Corporation)Figure7of11Sci-Mix attendees stopped by the ACS local section showcase station to snap a photo with a large frame. (Credit: Event Photography of North America Corporation)Figure8of11Students from the University of North Texas travel from one event to the next in the Indiana Convention Center. (Credit: Event Photography of North America Corporation)Figure9of11ACS CEO Albert G. Horvath addresses attendees at a reception hosted by the Office of Diversity, Equity, Inclusion, and Respect. (Credit: Event Photography of North America Corporation)Figure10of11There was lots to celebrate at ACS’s fourth hybrid meeting.

Abstract 2712: Killing cancer stem cells in 72 hours can cure breast cancer

Abstract Advancements in stem cell technology can open new doors for treating various diseases, disorders, and disabilities, including cardiovascular diseases, gastrointestinal diseases, liver diseases, arthritis, neurological disorder, and baldness. Though stem cell technology offers several answers to treat these ailments, the success of this technology is unfortunately daunted by the development of stem cells into cancer stem cells (CSC) and eventually into cancer cells. CSCs are hypothesized to be key drivers of cancer cells and apparent drug resistance to the current anticancer drugs. Therefore, a drug that can kill the CSC within 72 hours can open a new window of success for stem cell therapy for treating severe diseases to a much simpler disorders such as baldness. Herein, we present the application of the recently reported ID-Checker technology (Journal of Medicinal Chemistry 2022 65 (19), 12883-12894) for killing CSC. ID-Checker possesses a glucose tag that ensures its highly specific absorption and macroscale delivery of anticancer agents into the CSCs through GLUT channels. ID-Checker kills the cancer cells within 72 hours. ID-Checker inhibits the microtubule formation and GLUT channel deployment in 6 h and kills the CSCs without damaging normal cells. Citation Format: Keum-soo Song, Satish Balasaheb Nimse, Taisun Kim. Killing cancer stem cells in 72 hours can cure breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2712.

Abstract 1990: Targeting cancer stem cells is an answer to the curing lung cancer

Abstract Lung cancer is the leading cause of cancer-related mortality worldwide. Mainly, non-small cell lung cancer (NSCLC, about 80% of cases) and small cell lung cancer (SCLC, about 20% of cases) are the major types of lung cancer. Adenocarcinoma (30-50%) and squamous cell carcinoma (30%) are the major subtypes of NSCLC. Even though there are considerable advancements in the drugs against lung cancer, the 5-year survival rate is meager. Unfortunately, the drug resistance for currently available anticancer drugs results in a 5-year survival of only 5%. The remarkable lung cancer recurrence despite definitive local and/or systemic therapy indicate that residual cancer stem cells (CSCs) possess tumorigenic potential. Therefore, drugs targeting the CSCs and killing them quickly can cure lung cancer without any relapse and improve the 5-year survival rate. Herein, we present the application of the recently reported ID-Checker technology (Journal of Medicinal Chemistry 2022 65 (19), 12883-12894) for killing lung cancer stem cells (LCSC). The ID-Checker that is decorated with the glucose tag allows highly specific absorption and macroscale delivery of anticancer drugs to the LCSC through the GLUT channels. ID-Checker inhibits the microtubule formation resulting in the cell cycle arrest in the G2/M phase followed by apoptosis. The inhibition of microtubule formation by ID-Checker also leads to the inhibition of GLUT channel deployment in the LCSC. Thus, the glucose-deprived LCSC undergoes apoptosis within 72 hours of ID-Checker treatment. Hence, we believe the ID-Check technology presented here can kill the LCSC and completely cure lung cancer. Citation Format: Keum-Soo Song, Satish Balasaheb Nimse, Taisun Kim. Targeting cancer stem cells is an answer to the curing lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1990.

Some Observations and Guidance on Perspectives in the Journal of Medicinal Chemistry

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTSome Observations and Guidance on Perspectives in the Journal of Medicinal ChemistryDean G. Brown*Dean G. Brown*[email protected]More by Dean G. Brownhttps://orcid.org/0000-0002-7130-3928, Nicholas A. Meanwell*Nicholas A. Meanwell*[email protected]More by Nicholas A. Meanwellhttps://orcid.org/0000-0002-8857-1515, and Craig W. Lindsley*Craig W. Lindsley*[email protected]More by Craig W. Lindsleyhttps://orcid.org/0000-0003-0168-1445Cite this: J. Med. Chem. 2023, 66, 4, 2209–2210Publication Date (Web):February 15, 2023Publication History Received6 February 2023Published online15 February 2023Published inissue 23 February 2023https://doi.org/10.1021/acs.jmedchem.3c00208Copyright © 2023 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2955Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (846 KB) Get e-AlertsSUBJECTS:Chemical structure,Drug discovery,Heterocyclic compounds,Medicinal chemistry,Quality management Get e-Alerts

Trends and hotspots for European Journal of Medicinal Chemistry: A bibliometric study

European Journal of Medicinal Chemistry (EJMC) has been around for a long time and has gained broad interest from the various individuals working in the field. However, there is no bibliometric analysis on the publications of EJMC to thoroughly assess the scientific output and current status systematically. Therefore, the study was conducted to analyze the various publications of EJMC from 1987 to 2022 to improve their quality. A total of 13,386 papers were retrieved, with the number of publications increasing yearly. Based on the multiple indicators of bibliometrics, the highest impact countries, institutions, authors and representative literature were identified, and visualization networks were constructed using VOSviewer. Keyword co-occurrence analysis reveals a gradual shift from phenotypic drug discovery to target-based drug discovery in the EJMC theme change. Moreover, further discussion of the keyword clustering results is provided to support researchers in defining the scope of their research topics and planning their research directions. At this stage, there is a greater focus on developing antitumor and oxidative stress-related drugs than on the earlier anti-infective activities. In future studies, the main research directions are tumor multidrug resistance, oxidative stress, and dual inhibitors.

Australia’s Pharmacology Research: A Scientometric Assessment of High-Cited Papers During 2002–2021

Objectives To analyze Australia’s high-cited papers (HCPs) receiving ≥100 citations in pharmacology during 2002–2021 and examine the research characteristics, study performance of the top 30 leading participating organizations and authors, and identification of top 30 journals publishing in this area and sub-fields of their research. Materials and Methods Australia’s HCPs on pharmacology research from the top 30 most productive organizations were identified and extracted from the Scopus database from 2002 to 2021 on 21 September 2022 using a search strategy. Select bibliometric measures were utilized to evaluate the publication productivity of important players in this area. The network analysis was performed to evaluate the collaborative interactions amongst the countries, organizations, authors, and keywords. Results Of the 19,418 Australia’s publications (articles) in pharmacology from the top 30 most productive organizations during 2002–2022, only 685 (3.53%) were HCPs, which together received 1,14,623 citations, averaging 164.4 citations per paper (CPP) and the citations ranged from 100 to 1,230. Two papers had more than 1,000 citations and 16 papers had 500 citations. Of the 685 HCPs, 40.58% (278) and 11.39% (78) received external funding support and were international collaboratives. The most productive organizations were Monash University (n = 155), the University of Queensland (n = 111) and the University of Melbourne (n = 97). The most impactful organizations in terms of CPP and relative citation index (RCI) were James Cook University (203.22 and 1.21), Australian National University (196.67 and 1.18) and Queensland University of Technology (193.45 and 1.16). The most productive authors were J. Li (n = 24), C. J. H. Porter (n = 24) and R. L. Nation (n = 23) (Monash University, Melbourne); and the most impactful authors in terms of CPP were A. Christopoulos (Monash Institute of Pharmaceutical Sciences, Melbourne) (288.21), C.W. Pouton (Monash University, Melbourne) (241.50), and D.L. Peterson (University of Queensland, Brisbane) (225.58). The most productive journals were Antimicrobial Agents and Chemotherapy (n = 59), Environmental Pollution (n = 43) and Journal of Medicinal Chemistry (n = 42). The most impactful journals in terms of CPP were Nature Reviews Drug Discovery (371.8), Antiviral Research (286.86) and European Journal of Pharmaceutical Sciences (253.0). The most important keywords with their frequency of appearances were Animal Experiments (108), Metabolism (76), Drug Effects (67), Animal Models (65), Protein Expression (64), Anti-Bacterial Agents (62), Drug Delivery Systems (54), Drug Formulation (44), Signal Transduction (42), and so on. Conclusion There is an urgent need to increase national funding and expand international collaboration in priority areas, which will help to increase and diversify research output and improve research impact.

Toxicity of heroin laced with synthetic opioid β-U10 and etizolam

Illicit heroin can be substituted or adulterated with New Psychoactive Substances (NPS) including highly potent fentanyl-type substances or other opioid-like compounds to counteract low-purity supply. The addition of unknown NPS to the heroin supply poses an additional risk of overdose and death. In 2020, the Emerging Drug Network of Australia VIC (EDNAV) study was funded to monitor drug related harm in individuals attending emergency departments (ED) at major hospitals within Victoria. In September 2020, a previously unreported NPS, β-U10 (2-napthyl-U-47700), was detected in discarded drug paraphernalia samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia. Subsequently, blood samples of EDNAV project individuals with positive heroin detections were analysed for β-U10, in addition to NPS and traditional illicit drugs. After liquid-liquid extraction, blood samples underwent extensive toxicological analysis via targeted liquid-chromatography tandem mass spectrometry (LC-MS/MS) and untargeted screening via high-resolution quadrupole time-of-flight mass spectrometry (LC-QTOF). Confirmation of β-U10 concentrations were measured via LC-MS/MS using certified reference material. In total, seven cases were found to contain synthetic opioid β-U10. Six samples were collected in October 2020, with the remaining case detected more than a year later in December 2021. Measured β-U10 concentrations ranged from 0.01 to 22 ng/mL (median 3 ng/mL). All cases also contained methylamphetamine and etizolam. Morphine was detected in all cases along with 6-acetylmorphine in three of these cases. Other drugs included diphenhydramine, diazepam, doxylamine, gamma-hydroxybutyrate, MDMA, methadone, and mitragynine. The average age was 37 and ranged from 20 to 52 years of age. All individuals presented to ED with varying levels of sedation (Glascow Coma Scale 3–14, median 9) and recovered with supportive care (median stay 6.8 hours). Two cases showed a positive response to naloxone. The Poisons Severity Score for one case was 3, with 4 cases assessed as level 2. The pharmacological activity of β-U10 is largely unknown. β-U10 was first published by the Upjohn Company in the 1970's and is a structural analogue of the widely reported NPS U-47700, which has approximately seven times greater affinity to the μ-opioid receptor than morphine (Cheney. Journal of Medicinal Chemistry 1985;28:1853–1864). U-47700 has been utilised recreationally for its sedative properties in addition to positive effect on mood. The co-ingestion of other sedatives and respiratory depressants, including opioids and the NPS benzodiazepine etizolam in each of these reported cases precludes definitive conclusions regarding the clinical effect of β-U10. Additional studies that examined heroin supply at the time found the addition of β-U10 was associated with a decrease in heroin purity. The detection of β-U10 in one case 12 months following the previous detection may indicate the drug re-supply of the adulterated mixture in Australia. The detection of β-U10 has also informed toxicological investigations into heroin-related deaths that occurred during the same time-period. The consumption of adulterated illicit substances by unsuspecting individuals with unknown compounds such as β-U10, particularly in conjunction with other opioids and CNS depressants such as etizolam, is an alarming trend and poses a significant public health risk.

In vitro and in silico Screening of Bioactive Compounds from Jasminum subtriplinerve Blume as α-glucosidase Inhibitor

The leaves of Jasminum subtriplinerve Blume were extracted by cold maceration with ethanol 70 % and subsequently fractionated with n-hexane, ethyl acetate (EtOAc), and n-butanol (n-BuOH) solvents. The extract and fractions were evaluated α-glucosidase inhibitory activities in vitro. The results have shown that n-hexane and EtOAc fractions had strong α-glucosidase inhibitory effects with IC50 values of 7.27 ± 0.71 mg/mL and 7.42 ± 0.95 mg/mL, respectively. The total extract, the n-BuOH fraction, and the aqueous fraction did not show inhibitory effects on the enzyme α-glucosidase. The molecular docking results revealed that rutin, isoverbascoside, astragalin, isoquercitrin, verbascoside, stigmasterol, nicotiflorin, and chevangin B might play an important role in the biological effect of this medicinal plant. Among these compounds, astragalin, isoquercitrin, verbascoside, and stigmasterol may be developed as drugs. Our findings suggested that leaves of Jasminum subtriplinerve Blume will be the potent resource of natural α-glucosidase inhibitors.
 Keywords: α- glucosidase, diabetes, Jasminum subtriplinerve, molecular docking.
 References
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Α-Glucosidase Inhibition by Isolated Acylated Anthocyanins, Journal of Agricultural and Food Chemistry, Vol. 49, No. 4, 2001, pp. 1952-1956.[5] D. H. Ngan, H. T. C. Hoai, L. M. Huong, P. E. Hansen, O. Vang, Bioactivities and Chemical Constituents of A Vietnamese Medicinal Plant Che Vang, Jasminum Subtriplinerve Blume (Oleaceae), Natural Product Research Vol. 22, No. 11, 2008, pp. 942-949.[6] F. M. Afrapoli, B. Asghari, S. Saeidnia, Y. Ajani, M. Mirjani, M. Malmir et al., In Vitro Α-Glucosidase Inhibitory Activity of Phenolic Constituents from Aerial Parts of Polygonum Hyrcanicum, Daru Journal Of Pharmaceutical Sciences, Vol. 20, No. 37, 2012, pp. 1-6.[7] H. Tang, L. Huang, C. Sun, D. Zhao, Exploring the Structure–Activity Relationship and Interaction Mechanism of Flavonoids and Α-Glucosidase Based on Experimental Analysis and Molecular Docking Studies, Food & Function Vol. 11, No. 4, 2020, pp. 3332-3350.[8] K. Yamamoto, H. Miyake, M. Kusunoki, S. Osaki, Crystal Structures of Isomaltase from Saccharomyces Cerevisiae and in Complex with its Competitive Inhibitor Maltose, The Febs Journal, Vol. 277, No. 20, 2010, pp. 4205-4214.[9] A. Nokhala, M. J. Siddiqui, Q. U. Ahmed, M. S. A. Bustamam, Z. A. Zakaria, Investigation of Α-Glucosidase Inhibitory Metabolites from Tetracera Scandens Leaves by Gc–Ms Metabolite Profiling and Docking Studies. Biomolecules, Vol. 10, No. 287, 2020, pp. 1-17.[10] D. N. Dai, T. D. Thang, I. A. Ogunwande, O. A. Lawal, Study on Essential Oils from the Leaves of Two Vietnamese Plants: Jasminum Subtriplinerve Cl Blume and Vitex Quinata (Lour) Fn Williams, Natural Product Research, Vol. 30, No. 7, 2016, pp. 860-864.[11] N. T. H. Huong, N. K. Q. Cu, T. V. Quy, C. Zidorn, M. Ganzera, H. Stuppner, A New Phenylpropanoid Glycoside from Jasminum Subtriplinerve Blume, Journal of Asian Natural Products Research, Vol. 10, No. 11, 2008, pp. 1035-1038.[12] K. E. Hevener, W. Zhao, D. M. Ball, K. Babaoglu, J. Qi, S.W. White et al., Validation of Molecular Docking Programs for Virtual Screening Against Dihydropteroate Synthase, Journal of Chemical Information and Modeling Vol. 4, No. 2, 2009, pp. 444-460.[13] C. A. Lipinski, Lead-and Drug-Like Compounds: The Rule-of-Five Revolution, Drug Discovery Today: Technologies, Vol. 1, No. 4, 2004, pp. 337-341.[14] B. Jayaram, T. Singh, G. Mukherjee, A. Mathur, S. Shekhar, V. Shekhar, Eds. Sanjeevini: A Freely Accessible Web-Server For Target Directed Lead Molecule Discovery, Proceedings of the BMC Bioinformatics, Vol. 13, No. 17S7, 2012, pp. 1-13.[15] D. E. Pires, T. L. Blundell, D. B. Ascher. Pkcsm: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties using Graph-Based Signatures, Journal of Medicinal Chemistry, Vol. 58, No. 9, 2015, pp. 4066-4072.[16] R. Shukla, V. Pandey, G. P. Vadnere, S. Lodhi, Role of Flavonoids in Management of Inflammatory Disorders, in: Bioactive Food as Dietary Interventionsfor Arthritis and Related Inflammatory Diseases, Elsevier, 2019, pp. 293-322.[17] H. C. Hong, S. L. Li, X. Q. Zhang, W. C. Ye, Q. W. Zhang, Flavonoids with Α-Glucosidase Inhibitory Activities and Their Contents in the Leaves of Morus Atropurpurea, Chinese Medicine, Vol. 8, No. 1, 2013, pp. 1-7.[18] K. Valentová, J. Vrba, M. Bancířová, J. Ulrichová, V. Křen, Isoquercitrin: Pharmacology, Toxicology, and Metabolism, Food and Chemical Toxicology, Vol. 68, 2014, pp. 267-282.[19] P. Aparna, A. K. Tiwari, P. V. Srinivas, A. Z. Ali, V. Anuradha, J. M. Rao, Dolichandroside A, A New Α‐Glucosidase Inhibitor and Dpph Free‐Radical Scavenger from Dolichandrone Falcata Seem, Phytotherapy Research: an International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, Vol. 23, No. 4, 2009, pp. 591-596.[20] S. Tasnuva, U. Qamar, K. Ghafoor, F. Sahena, M. Jahurul, A. Rukshana et al., Α-Glucosidase Inhibitors Isolated from Mimosa Pudica L. Natural Product Research, Vol. 33, No. 10, 2019, pp. 1495-1499.[21] C. H. Jhong, J. Riyaphan, S. H. Lin, Y. C. Chia, C. F. Weng, Screening Alpha‐Glucosidase and Alpha‐Amylase Inhibitors from Natural Compounds by Molecular Docking in Silico, Biofactors, Vol. 41, No. 4, 2015, pp. 242-251.
  
  

2022: Celebrating the 65th Publication Volume of the Journal of Medicinal Chemistry.

ADVERTISEMENT RETURN TO ISSUEEditorialNEXT2022: Celebrating the 65th Publication Volume of the Journal of Medicinal ChemistryCraig W. LindsleyCraig W. LindsleyMore by Craig W. Lindsleyhttps://orcid.org/0000-0003-0168-1445Cite this: J. Med. Chem. 2022, 65, 1, 1Publication Date (Web):December 29, 2021Publication History Published online29 December 2021Published inissue 13 January 2022https://doi.org/10.1021/acs.jmedchem.1c02170Copyright © 2021 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1020Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (433 KB) Get e-AlertsSUBJECTS:Medicinal chemistry,Interfaces,Organic chemistry,Pharmaceuticals,Drug discovery Get e-Alerts

How Diverse Is Medicinal Chemistry? Insights into Race, Ethnicity, Origin, Gender, and Geography.

A bibliometric study of authors across medicinal chemistry journals over 20 years reveals important trends. Most United States (US) based authors are assigned as racially/ethnically Asian or White; few are Black or Hispanic. More US coauthors have the same race/ethnicity as the corresponding author than expected. The percentage of female authors increased globally, but only slowly. Since 2010, the number of female and male authors declined by 9% and 30%, respectively. Geographically, most authors are male except in Italy where there is gender balance. Gender homophily is observed globally. Geographically, the discipline is now more widely practiced. Article output doubled from 2000 to 2010 with a large increase in articles from China. China excepted, output has since declined. The average number of authors per article rose by a third since 2000. The value of high diversity groups in education, research, and industry cannot be overstated. We recommend diversity is addressed by every medicinal chemist.

New Heights for ProTides?

In this issue of the Journal of Medicinal Chemistry, Janeba et al. found that the in vitro antiviral activity and selectivity index of the aryloxy phosphoramidate (ProTide) prodrug of the acyclic nucleoside phosphonate tenofovir (tenofovir alafenamide) can be dramatically improved by replacing the aryloxy pro-moiety with an appropriate tyrosine derivative. This Viewpoint highlights the possible impact and ramifications that these findings may have in the development of new ProTides.

The Potential of Medicinal Plants and Bioactive Compounds in the Fight Against COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus , is causing a serious worldwide COVID-19 pandemic. The emergence of strains with rapid spread and unpredictable changes is the cause of the increase in morbidity and mortality rates. A number of drugs as well as vaccines are currently being used to relieve symptoms, prevent and treat the disease caused by this virus. However, the number of approved drugs is still very limited due to their effectiveness and side effects. In such a situation, medicinal plants and bioactive compounds are considered a highly valuable source in the development of new antiviral drugs against SARS-CoV-2. This review summarizes medicinal plants and bioactive compounds that have been shown to act on molecular targets involved in the infection and replication of SARS-CoV-2.
 Keywords: Medicinal plants, bioactive compounds, antivirus, SARS-CoV-2, COVID-19
 References
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Uesato, Antiviral Activity of Berberine and Related Compounds Against Human Cytomegalovirus, Bioorganic & Medicinal Chemistry Letters, Vol. 17, No. 6, 2007, pp. 1562-1564, https://doi.org/10.1016/j.bmcl.2006.12.085.[88] A. Warowicka, R. Nawrot, A. Gozdzicka Jozefiak, Antiviral Activity of Berberine, Archives of Virology, Vol. 165, No. 9, 2020, pp. 1935-1945, https://doi.org/10.1007/s00705-020-04706-3.[89] Z. Z. Wang, K. Li, A. R. Maskey, W. Huang, A. A. Toutov, N. Yang et al., A Small Molecule Compound Berberine as an Orally Active Therapeutic Candidate Against COVID-19 and SARS: A Computational and Mechanistic Study, FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, Vol. 35, No. 4, 2021, pp. e21360-21379, https://doi.org/10.1096/fj.202001792R.[90] A. Pizzorno, B. Padey, J. Dubois, T. Julien, A. Traversier, V. Dulière et al., In Vitro Evaluation of Antiviral Activity of Single and Combined Repurposable Drugs Against SARS-CoV-2, Antiviral Research, Vol. 181, No. 104878, 2020, https://doi.org/10.1016/j.antiviral.2020.104878.[91] B. Y. Zhang, M. Chen, X. C. Chen, K. Cao, Y. You, Y. J. Qian et al., Berberine Reduces Circulating Inflammatory Mediators in Patients with Severe COVID-19, The British Journal of Surgery, Vol. 108, No. 1, 2021, pp. e9-e11, https://doi.org/10.1093/bjs/znaa021.[92] K. P. Latté, K. E. Appel, A. Lampen, Health Benefits and Possible Risks of Broccoli - an Overview, Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, Vol. 49, No. 12, 2011, pp. 3287-3309, https://doi.org/10.1016/j.fct.2011.08.019.[93] C. Sturm, A. E. 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Miller DeGraff, D. Walters, G. A. Melendi, M. Yamamoto et al., Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease, American Journal of Respiratory and Critical Care Medicine, Vol. 179, No. 2, 2009, pp. 138-150, https://doi.org/10.1164/rccm.200804-535OC.[98] M. J. Kesic, S. O. Simmons, R. Bauer, I. Jaspers, Nrf2 Expression Modifies Influenza A Entry and Replication in Nasal Epithelial Cells, Free Radical Biology & Medicine, Vol. 51, No. 2, 2011, pp. 444-453, https://doi.org/10.1016/j.freeradbiomed.2011.04.027.[99] A. Cuadrado, M. Pajares, C. Benito, J. J. Villegas, M. Escoll, R. F. Ginés et al., Can Activation of NRF2 Be a Strategy Against COVID-19?, Trends in Pharmacological Sciences, Vol. 41, No. 9, 2020, pp. 598-610, https://doi.org/10.1016/j.tips.2020.07.003.[100] J. Gasparello, E. D'Aversa, C. Papi, L. Gambari, B. Grigolo, M. 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Evaluating Protein Tyrosine Phosphatase 1B Inhibitory Activity of Bioactive Compounds from Momordica charantia for Diabetes Treatment Type 2 by using Molecular Docking Method

Diabetes mellitus is a chronic metabolic disease, which is characterized by elevated blood glucose levels, caused by a deficiency in insulin secretion from the β pancreatic’s cells or the operability of insulin. The protein tyrosine phosphatase 1B (PTP1B) catalyzes to removing the phosphate group from the insulin receptor's phosphotyrosine, then reducing insulin’s effects. Therefore, inhibiting this enzyme is an effective method to treat diabetes mellitus. Momordica charantia is effective in the treatment of diabetes mellitus. In this study, we evaluated the inhibitory effects of PTP1B enzyme of Momordica charantia’s compounds by using molecular docking method. Based on the previous publication of Momordica charantia, we have collected 57 compounds. The results showed that 3 compounds have PTP1B inhibitory effect stronger than the positive control including Luteolin-7-O-glycoside, apigenin-7-O-glycoside and δ-cadinene. Analysis Lipinski Rule of Five showed that Luteolin-7-O-glycoside and δ-cadinene have drug-likeness properties. Moreover, predict ADMET showed that these two compounds have good intestinal absorption, not metabolized in the liver, excretion by the kidney and low toxicity. Conclusion: Our findings suggested that luteolin-7-O-glycoside, δ-cadinene may be potential natural product compounds for diabetes treatment type 2.
 Keywords
 Momordica charantia, PTP1B, Diabetes mellitus, Molecular docking, in silico.
 References
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Kennedy, Therapeutic Strategies for Targeting PTP1B in Diabetes, Drug Discovery Today: Therapeutic Strategies, Vol. 2, No. 2, 2005, pp. 129-135, https://doi.org/10.1016/j.ddstr.2005.05.002. [7] S. Jia, M. Shen, F. Zhang, J. Xie, Recent Advances in Momordica charantia: Functional Components and Biological Activities, International Journal of Molecular Sciences, Vol. 18, No. 12, 2017, pp. 2555, https://doi.org/10.3390/ijms18122555.[8] P. Kulkarni, S. Lohidasan, K. Mahadik, Isolation, Characterisation and Investigation of in vitro Antidiabetic and Antioxidant Activity of Phytoconstituents from Fruit of Momordica charantia Linn, Natural Product Research, Vol. 35, No. 6, 2019, pp. 1035-1037, https://doi.org/10.1080/14786419.2019.1613400.[9] Z. Liu, J. Gong, W. Huang, F. Lu, H. Dong, The Effect of Momordica charantia in the Treatment of Diabetes Mellitus: A Review, Evidence-Based Complementary and Alternative Medicine, Vol. 2021, 2021, pp. 1-14, https://doi.org/10.1155/2021/3796265. [10] X. Y. Meng, H. X. Zhang, M. Mezei, M. Cui, Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery, Current Computer-Aided Drug Design, Vol. 7, No. 2, 2011, pp. 146-157, https://doi.org/10.2174/157340911795677602.[11] B. K. Shoichet, S. L. McGovern, B. Wei, J. J. Irwin, Lead Discovery Using Molecular Docking, Current Opinion in Chemical Biology, Vol. 6, No. 4, 2002, pp. 439-446, https://doi.org/10.1016/S1367-5931(02)00339-3.[12] C. A. Lipinski, Lead-and Drug-like Compounds: the Rule-of-five Revolution, Drug Discovery Today: Technologies, Vol. 1, No. 4, 2004, pp. 337-341, https://doi.org/10.1016/j.ddtec.2004.11.007.[13] B. Jayaram, T. Singh, G. Mukherjee, A. Mathur, S. Shekhar, V. Shekhar, Sanjeevini: A Freely Accessible Web-server for Target Directed Lead Molecule Discovery, Eleventh International Conference on Bioinformatics (InCoB2012): Bioinformatics, Vol. 13, 2012. pp. 1-13, https://doi.org/10.1186/1471-2105-13-s17-s7. [14] D. E. Pires, T. L. Blundell, D. B. Ascher. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures, Journal of Medicinal Chemistry, Vol. 58, No. 9, 2015, pp. 4066 - 4072, https://doi.org/10.1021/acs.jmedchem.5b00104.[15] A. Braca, T. Siciliano, M. D’Arrigo, M. P. Germanò, Chemical Composition and Antimicrobial Activity of Momordica charantia Seed Essential Oil, Fitoterapia, Vol. 79, No. 2, 2008, pp. 123-125, https://doi.org/10.1016/j.fitote.2007.11.002. [16] S. Sur, R. B. Ray. Bitter Melon (Momordica Charantia), A Nutraceutical Approach for Cancer Prevention and Therapy, Cancers, Vol. 12, No. 8, 2020, pp. 2064, https://doi.org/10.3390/cancers12082064. [17] L. Harinantenaina, M. Tanaka, S. Takaoka, M. Oda, O. Mogami, M. Uchida, Y. Sakawa, Momordica charantia Constituents and Antidiabetic Screening of the Isolated Major Compounds, Chemical and Pharmaceutical Bulletin, Vol. 54, No. 7, 2006, pp. 1017-1021, https://doi.org/10.1248/cpb.54.1017.[18] K. A. Lantz, S. G. E. Hart, S. 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Hogger, Dietary Polyphenols and Type 2 Diabetes: Current Insights and Future Perspectives, Current Medicinal Chemistry, Vol. 22, No. 1, 2015, pp. 23-38, https://doi.org/10. 2174/0929867321666140706130807.[22] Y. Zang, K. Igarashi, Y. Li, Anti-diabetic Effects of Luteolin and Luteolin-7-O-glucoside on KK-Ay Mice; Bioscience, Biotechnology, and Biochemistry, Vol. 80, No. 8, 2016, pp. 1580-1586, https://doi.org/10.1080/09168451.2015.1116928.
  

Craig Lindsley leads Journal of Medicinal Chemistry

Craig Lindsley leads Journal of Medicinal Chemistry

Craig Lindsley named editor in chief of the Journal of Medicinal Chemistry

Craig Lindsley named editor in chief of the <i>Journal of Medicinal Chemistry</i>

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OPINION Reactions ShareShare onFacebookTwitterWechatLinked InRedditEmail C&EN, 2021, 99 (9), p 3March 15, 2021Cite this:C&EN 99, 9, 3Letters to the editorCOVID-19 special issueI was blown away by the Jan. 18/25, 2021, edition on COVID-19. The entire issue was extremely thorough, well written, well edited, and incredibly informative. This is the most standout issue I have come across in my 30 years as a member. It was true journalistic excellence, and hopefully all those involved will be nominated for awards in journalism. Kudos to all involved.Brad SavallSan DiegoACS and death penaltyThe recently appointed editor in chief (EIC) of the distinguished Journal of Medicinal Chemistry, who is also the interim EIC of ACS Pharmacology and Translational Science and formerly the EIC of ACS Chemical Neuroscience, was one of two medical experts consulted by the US Department of Justice in 2017 regarding the constitutionality of an execution protocol for federal prisoners convicted of capital crimes and sentenced to death. According to publicly available documents, this protocol involves administration of 2 × 2.5 g of pentobarbital sodium in 50 mL of diluent followed by 60 mL of saline flush, after which the “inmate will be examined by a specified qualified person . . . to ensure that death has occurred.”Under a letterhead that included his position as EIC of ACS Chemical Neuroscience, the EIC advised in a publicly available document, “In my expert opinion, based on deep knowledge of the pharmacology of pentobarbital sodium, the protocol as drafted will produce a humane death with limited suffering and pain.”According to records at the Death Penalty Information Center, this protocol was used to execute 13 federal prisoners during the final weeks of the Trump administration—6 Black men, 1 Native American man, 1 White woman, and 5 White men.These are not the pages in which the constitutionality of the death penalty should be debated. However, these are the pages in which it is right to question the association of the American Chemical Society and its journals with this debate. The constitution of our society declares that our purpose is to “be concerned with the worldwide application of chemistry to the needs of humanity.” In my opinion, our constitution is a moral compass, pointing toward a world in which our society and our chemistry must focus on how to improve human life, not how to end it.David W. ChristiansonPhiladelphia CorrectionsFeb. 1, 2021, page 12: In the news story on the US plan to join a treaty on hydrofluorocarbons, the last word of the caption is cut off. It should read “Joe Biden’s executive order on climate includes provisions on environmental justice.”March 8, 2021, page 23: The feature story on nonanimal leathers incorrectly identifies the mushroom leather sample shown in a photo. The product is called Mylea, not Mylo.

Screenning Bioactive Compounds from Allium sativum as HER2 Inhibitors Targeting Breast Cancer by Docking Methods

Background: HER2-positive breast cancer is a breast cancer that tests positive with human epidermal growth factor receptor 2 (HER2). Human Epidermal Growth Factor Receptor-2 (HER2) promotes the proliferation of breast cancers cells. This research aimed to find the bioactive compounds from Allium sativum for inhibiting HER2 enzyme by using molecular docking method. Materials and method: The protein tyrosin kinase HER2 structure was obtained from Protein Data Bank. Compounds were collected from previous publications of Allium sativum and these structures were retrieved from PubChem database. Molecular docking was done by Autodock vina software. Lipinski’s rule of 5 is used to compare compounds with drug-like and non-drug-like properties. Pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool. Results: Based on previous publication of Allium sativum, we have collected 55 compounds. The results showed that 2 compounds have HER2 inhibitory activity stronger than the reference compounds including biochanin A và cyanidin 3-malonylglucoside. The Lipinski’s rule of Five showed that these two compounds had propietary drug-likenesss. Moreover, predict ADMET of these compounds was also analyzed. Conclusion: Therefore, biochanin A and cyanidin 3-malonylglucoside may be potential natural product compounds for HER2-positive breast cancer treatment.&#x0D; Keywords:&#x0D; Allium sativum, tyrosin kinase HER2, breast cancer HER2 positive, in silico, molecular docking.&#x0D; References&#x0D; [1] S. Libson, M. Lippman. A review of clinical aspects of breast cancer. International review of psychiatry (Abingdon, England) 26(1) (2014) 4.[2] D.J. Slamon, G.M. Clark, S.G. Wong, W.J. Levin, A. Ullrich, W.L. McGuire. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785) (1987) 177.[3] U. Krishnamurti, J.F. Silverman. 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The Journal of biological chemistry 286(21) (2011) 18756.[14] V.M. Beato, F. Orgaz, F. Mansilla, A. Montaño. Changes in Phenolic Compounds in Garlic (Allium sativum L.) Owing to the Cultivar and Location of Growth. Plant Foods for Human Nutrition 66(3) (2011) 218.[15] M. Thomson, M. Ali. Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. 1568-0096 (Print)).[16] M.I. Alarcón-Flores, R. Romero-González, J.L. Martínez Vidal, A. Garrido Frenich. Determination of Phenolic Compounds in Artichoke, Garlic and Spinach by Ultra-High-Performance Liquid Chromatography Coupled to Tandem Mass Spectrometry. Food Analytical Methods 7(10) (2014) 2095.[17] A.D. Phan, G. Netzel, P. Chhim, M.E. Netzel, Y. Sultanbawa. Phytochemical Characteristics and Antimicrobial Activity of Australian Grown Garlic (Allium Sativum L.) Cultivars. Foods 8(9) (2019).[18] M. Ichikawa, N. Ide, J. Yoshida, H. Yamaguchi, K. Ono. 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Sanjeevini: a freely accessible web-server for target directed lead molecule discovery. Proceedings of the BMC bioinformatics; 2012. Springer (Year).[28] D.E. Pires, T.L. Blundell, D.B. Ascher. pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry 58(9) (2015) 4066.[29] A. Lee. Tucatinib: First Approval. Drugs 80(10) (2020) 1033.[30] B. Moy, P. Kirkpatrick, S. Kar, P. Goss. Lapatinib. Nature Reviews Drug Discovery 6(6) (2007) 431.[31] M.G. Cesca, L. Vian, S. Cristóvão-Ferreira, N. Pondé, E. de Azambuja. HER2-positive advanced breast cancer treatment in 2020. 1532-1967 (Electronic)).[32] M. Shah, S. Wedam, J. Cheng, M.H. Fiero, H. Xia, F. Li, et al. FDA Approval Summary: Tucatinib for the Treatment of Patients with Advanced or Metastatic HER2-Positive Breast Cancer. Clinical Cancer Research(2020) clincanres.2701.2020.[33] P. Wu, T.E. Nielsen, M.H. Clausen. FDA-approved small-molecule kinase inhibitors. 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Long-Acting Injectables Come of Age to Change the HIV Therapeutic Landscape and the Lives of Persons with HIV.

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