Commercial Drug Research Articles

Befunolol as a potential inhibitor of glycogen phosphorylase: an in silico approach

Glycogen phosphorylase (GP) is a rate-limiting allosteric enzyme in the glycogenolysis pathway that contributes to hyperglycemia in type 2 diabetes (T2D). Hence, researchers consider GP a validated target to treat T2D. Commercial antidiabetic drugs are effective but have undesirable effects. Our search for a safer drug led us to investigate a potential GP inhibitor that could modulate blood glucose levels with minimal or no side effects. Herein, we report seven structural analogs of the reference compound N-acetyl-beta-D-glucopyranosyl amine (NBG) (analog of D-glucose) targeting the active site of human liver GPa (PDB ID: 1FC0). In silico molecular docking studies were conducted to predict GPa-ligand interactions. We analyzed drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters using AutoDock 4.2, Discovery Studio, SwissADME, ProTox-II, and ADMETlab web tools. Among all compounds, befunolol (−8.83 kcal/mol) exhibited the highest affinity than NBG (−6.20 kcal/mol) for the binding pocket of GPa and inferred a good pharmacokinetic profile. Toxicological endpoint prediction analysis showed befunolol as a non-hERG blocker and non-carcinogenic with a drug score (0.95) higher than NBG (0.30) and an LD50 value of 922 mg/kg. A molecular dynamics simulation of befunolol and NBG for 100 ns using Schrödinger software revealed the stability of protein-ligand complexes. Overall, our findings suggest that befunolol could represent a potential therapeutic drug candidate worth exploring in cell-based and pre-clinical studies.

DNA barcoding combined with high-resolution melting analysis to discriminate rhubarb species and its traditional Chinese patent medicines.

Introduction: Rhubarb is a frequently used and beneficial traditional Chinese medicine. Wild resources of these plants are constantly being depleted, meaning that rhubarb products have been subjected to an unparalleled level of adulteration. Consequentially, reliable technology is urgently required to verify the authenticity of rhubarb raw materials and commercial botanical drugs. Methods: In this study, the barcode-DNA high-resolution melting (Bar-HRM) method was applied to characterize 63 rhubarb samples (five Polygonaceae species: Rheum tanguticum, Rh. palmatum, Rh. officinale, Rumex japonicus and Ru. sp.) and distinguish the rhubarb contents of 24 traditional Chinese patent medicine (TCPM) samples. Three markers, namely ITS2, rbcL and psbA-trnH, were tested to assess the candidate DNA barcodes for their effectiveness in distinguishing rhubarb from its adulterants. A segment from ITS2 was selected as the most suitable mini-barcode to identify the botanical drug rhubarb in TCPMs. Then, rhubarbs and TCPM samples were subjected to HRM analysis based on the ITS2 barcode. Results: Among the tested barcoding loci, ITS2 displayed abundant sites of variation and was effective in identifying Polygonaceae species and their botanical origins. HRM analysis based on the ITS2 mini-barcode region successfully distinguished the authenticity of five Polygonaceae species and eight batches of TCPMs. Of the 18 TCPM samples, 66.7 % (12 samples) were identified as containing Rh. tanguticum or Rh. officinale. However, 33.3 % were shown to consist of adulterants. Conclusions: These results demonstrated that DNA barcoding combined with HRM is a specific, suitable and powerful approach for identifying rhubarb species and TCPMs, which is crucial to guaranteeing the security of medicinal plants being traded internationally.

Anti-cancer drug axitinib: a unique tautomerism-induced dual-emissive probe for protein analysis.

A commercial anti-cancer drug, axitinib, exhibits very stable dual emissions for discrimination of human serum albumin.

The biopotential of extremophilic microorganisms isolated from Kuzbass for protection and growth stimulation of oat (Avena sativa L.)

Biological plant protection products are extensively utilized in agriculture owing to their safety, efficacy, and environmental friendliness. The utilization of these funds in locales with challenging weather patterns is constrained. In order to ensure the successful use of biological plant protection products, it is rational to search for microorganisms adapted to the specific soil and climatic conditions of the territory. The objective of the investigation is to evaluate the antagonistic and growth-stimulating properties of the consortium of extremophilic microorganisms of Kuzbass, and to conduct laboratory testing on oats (Avena sativa L.). The work used microorganisms isolated at the initial stages of the research, such as Leclercia sp., Sphingomonas paucimobilis, and Lactobacillus plantarum. The findings revealed that these microorganisms are capable of producing gibberellic acid, dissolving phosphates, and retaining atmospheric nitrogen. Furthermore, the co-cultivation of microorganisms facilitates the enhancement of these indicators. The negative impact of phytopathogens (Alternaria alternata (F-525), Fusarium graminearum (F-877) PH-1, Fusarium graminearum (F-892) and Fusarium sporotrichioides (F-902)) on oats in laboratory conditions was reduced by a consortium based on these microorganisms. Therefore, the consortium has the potential to develop commercial drugs. Field experiments are planned in the future.

Integrating molecular docking and molecular dynamics simulations to evaluate active compounds of Hibiscus schizopetalus for obesity

The group screened and identified the content of Hibiscus schizopetalus by protein–protein interaction, molecular docking, and dynamics as a potential therapy for obesity through pancreatic lipase (PNLIP) as a protein target. First, the group collected all active ingredients of H. schizopetalus from an online database [http://www.knapsackfamily. com/ and http://ijah.apps.cs.ipb.ac.id/] to identify and isolate active compounds. The 3-D structures and canonical of the active compound were taken from the PubChem database, and then all compounds were analyzed by pkCSM and Tox-Protox II to get pharmacokinetics and physical-chemistry properties. The protein target of obesity was identified using the Open Target Platform. After the protein targets of plant extract and obesity were collected, the group analyzed them using Cytoscape. Protein–protein interaction was analyzed using String, Gene ontology, and KEGG pathway. Virtual screening was done by Pyrx software, and visualization was done by Discovery Studio Biovia, proceed by molecular docking using AutoDockTools-1.5.7, and finally, molecular dynamics (MDs) was done using YASARA software. The group collected 70 compounds from a research journal and found 196 protein targets. The target of obesity was 165 protein targets. The 196 protein targets of H. schizopetalus and 165 protein targets were analyzed and merged using Cytoscape and 11 proteins targeting H. schizopetalus and obesity. After that, the group analyzed which compound of H. schizopetalus affected 11 protein targets by Pyrx with the highest binding affinity. PNLIP has the highest binding affinity compared to other proteins, so the group analyzed this PNLIP protein with its relationship to obesity. The group found that three proteins that work on PNLIP are beta-sitosterol, kaempferol, and gallocatechin gallate. After docking these three proteins, the group found only one active compound has the highest binding affinity compared to the commercial drug Orlistat. Then, the process ended by performing MDs of the active compound as a candidate drug for anti-obesity. In this study, the group found that gallocatechin gallate, as an active compound of H. schizopetalus, can inhibit PNLIP enzymes for obesity therapy by bio-informatics study.

Antimicrobial sesquiterpenes from the cultured mycobiont Diorygma pruinosum against methicillin-resistant Staphylococcus aureus isolated from Vietnamese street foods.

Traditionally, lichen has been used for many purposes, but there remains a lack of understanding regarding the chemical composition and antimicrobial characteristics of Diorygma pruinosum, a lichen native to Vietnam. In this study, four sesquiterpenes, diorygmones B-E (1-4), one phenolic compound, 3,5-dihydroxy-4-methoxybenzoic acid (5), and one sterol, β-sitosterol (6), were isolated and structurally elucidated from the cultured mycobiont of the lichen Diorygma pruinosum. Additionally, two compounds, stictic acid (7) and norstictic acid (8), were also isolated from the lichen D. pruinosum. Compounds 2-4 were new compounds. Their chemical structures were established using comprehensive spectroscopic data, and the absolute configurations were confirmed through the analysis of NOESY and electronic circular dichroism (ECD). Moreover, Staphylococcus aureus, a Gram-positive bacterium, has been responsible for various infections, including food poisoning. Herein, we identified and isolated 13 strains of S. aureus from street food sources. Among these strains, one was identified as a multidrug-resistant variant, designated as SAX15, and was subsequently used for further antimicrobial testing. Compounds 1-3 produced zones of inhibition against S. aureus SAX15 (each 5 mm) in comparison to commercial drugs such as penicillin, ciprofloxacin, gentamicin, cefoxitin, and clarithromycin, which displayed inhibitory zones of 7, 5, 10, 9.7, and 7 mm, respectively.

A phytic acid-based CoMn bimetallic metal-organic aerogel (PA-CoMn-1 : x : 2 - x) as a modifier for electrochemical detection of non-steroidal anti-inflammatory drug 4-acetaminophenol.

Metal phosphides and phosphate-based materials have received significant attention due to their high electrocatalytic activity, adjustable structure composition and stability. Herein, we introduce a phytic acid-based CoMn bimetallic metal-organic (PA-CoMn) aerogel as an electrode modifier, derived from PA and mixed transition metal ions (Co2+, Mn2+). We explored its performance in the sensitive sensing of non-steroidal anti-inflammatory drug 4-acetaminophenol (4-AP) for the first time. We investigated the electrochemical behavior of the modified screen-printed carbon electrode (SPCE) by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The PA-CoMn-1 : 1.5 : 0.5 aerogel/Nafion/SPCE proved to be highly sensitive and selective towards the detection of 4-AP. A double linear response was recorded for 4-AP over the range of 1 μM to 0.1 mM and lower detection limits (LOD) of 0.2133 μM. The applicability of the PA-CoMn-1 : 1.5 : 0.5 aerogel/Nafion/SPCE in the detection of 4-AP in commercial drug samples with good recoveries was investigated, confirming the great potential of PA-CoMn-1 : 1.5 : 0.5 aerogel/SPCE in clinical applications.

Evaluation of the Mineral, Amino Acid and Antimicrobial Properties of Raw and Fermented Trametes elegans

Mushrooms are known to be sources of food and bioactive compounds with medicinal properties. In this study, the mineral, proximate, amino acid and antimicrobial properties of a wild macrofungus, Trametes elegans was investigated. Standard methods were used to evaluate the mineral, proximate and amino acid content of raw and fermented T.elegans. By soaking in methanol and acetone, extracts from the macrofungus’s powdered fruiting bodies were obtained. Using common microbiological methods, the macrofungus extracts’ antimicrobial activity was assessed on test isolates. In addition, isolation and identification of microorganisms associated with raw and fermented T. elegans was done using standard microbiological techniques. The physicochemical parameters (Temperature, pH and Total Titratable Acid) were also monitored during solid and liquid state fermentation of Trametes elegans. The concentration of carbohydrate (70.24±0.33) was higher in the raw sample, while moisture (3.22±0.13), fat (1.85±0.04) and protein contents (22.48±0.09) were higher in sample subjected to solid fermentation. Also, crude fibre (6.68±0.76) and Ash (3.60±1.39) were higher in sample subjected to liquid fermentation. The micro elements analysed are zinc and iron and macro elements are potassium, magnesium and phosphorus and their values increased in fermented Trametes elegans. Analyses of both essential and non-essential amino acids were conducted. The most common amino acids found in all of the samples examined were glutamic acid, leucine, arginine, and aspartic acid. Cysteine and methionine are the least abundant. The amino acid scores were determined by ratio of the milligrams of amino acid per gram of test protein to the milligrams of amino acid per gram in the reference pattern. The results showed that methionine had the lowest score in the raw sample (3.14) and tryptophan had the highest score (18.17) in T. elegans that had undergone solid fermentation. Methanol and acetone extracts inhibited all test isolates except Lactobacillus plantarum. The commercial drug exhibited higher antibacterial activity compared to the extracts, with a significant difference (P≤ 0.05). The inhibitory zones ranged from 5.50 mm against Bacillus subtilis to 18.13 mm against E. coli. The range of the minimum bactericidal concentration (MBC) was 12.5 to 50 mg/mL, while the minimum inhibitory concentration (MIC) was 12.5 to 50 mg/mL. In light of this findings, T. elegans, could be considered as potential sources of natural antimicrobial and can also be relevant for use as food supplements in animals and man.

Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata.

Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2-3 W, 80-120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47-30.98 nm and 18.83-38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7-17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs.

Exploring hydrophilic 2,2-di(indol-3-yl)ethanamine derivatives against Leishmania infantum.

Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 μM. The most selective compound 1h (selectivity index = 10.1, comparable to miltefosine) and the most potent compound 2c (IC50 = 2.7 μM) were tested for their efficacy on L. infantum intracellular amastigotes. The compounds also demonstrated their efficacy in the in vitro infection model, showing IC50 of 11.1 and 6.8 μM for 1h and 2c, respectively. Moreover, 1h showed a better toxicity profile than the commercial drug miltefosine. For all these reasons, 1h could be a possible new starting point for hydrophilic antileishmanial agents with low cytotoxicity on human macrophage-like cells.

Molecular Docking of Bioactive Compounds from Thai Medicinal Plants Against Xanthine Oxidase for Gout Treatment

Xanthine oxidase (XO) is a crucial enzyme of the purine catabolism pathway, which catalyzes the reaction of hypoxanthine to xanthine and xanthine to uric acid. The high level of uric acid leads to gout, kidney disease, and several disorders. In this study, molecular docking was performed to investigate potential bioactive compounds from Thai medicinal plants that acted as XO inhibitors compared to commercial drugs. Among 30 bioactive compounds tested, 16 were classified as strong XO inhibitors. These compounds include asiatic acid, benzyl glucosinolate, beta-sitosterol, chlorogenic acid, curcumin, eupatorin, gamma-mangostin, hibiscitrin, lutein, nimbolide, piperine, quercetin, rosmarinic acid, rutin, sesamin, and vitexin. They exhibited binding affinity values ranging from -8.5 to -10.6 kcal/mol. Moreover, moderate XO inhibitors were identified with binding affinity of -6.2 to -8.0 kcal/mol, consisting of the 7 compounds of gallic acid, garcinia acid, gingerol, limonene, linalyl acetate, panduratin A, and scopoletin. As a result, Thai medicinal plants could serve as potential sources of bioactive compounds for further drug design for treating gout patients.

The Rational Use of Oxalic Acid Against to “Varroa Destructor”; Regional Scale Pilot Scheme

Varroa destructor mite poses a serious problem for the future of bee populations around the world. Today, there are many commercial drugs with the same and different active ingredients on the market to chemically control over of Varroa destructor. More frequent chemical applications for against Varroa destructor increases stress resilience, colony losses, loss of yield and residue problems in bee products. The scope of this project is aimed to determine the appropriate control method of Varroa by investigating the efficiency values of the evaporation and dropping methods of Oxalic acid. Experimental area were chosen three different apiaries. 28 colonies were determined in each apiary and equalization studies (area with brood, number of bees with bees, age of queen bees, honey, pollen, etc.) were carried out in these colonies. The determined colonies were randomly divided into 4 groups as 7 colonies. The first group is the control group, the second group is applying 2 g of oxalic acid by vaporizing, the third group is 4% oxalic acid 5 ml of sugar syrup (1:1) is dropped between the frames, and in the fourth group, the fight against a drug that is determined by the beekeeper in the market without interfering with the beekeeper. In order to evaluate the data, samples were taken for four periods, before and after spraying in spring and autumn. While the varroa measurements in the group of syrup, vapor and spraying were found to be statistically less than the control group, the syrup, vapor and spraying groups were statistically similar in terms of varroa measurements. Oxalic acid syrup application showed higher efficiency in spring and autumn than vapor application. There is no statistically difference between both two-application method reveals that it can be used as an effective and safe alternative to chemical control against varroa.

Ultrahigh-Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti-Angiogenic Therapy.

Ocular angiogenesis, associated with diseases such as retinopathy of prematurity and diabetic retinopathy, is a leading cause of irreversible vision loss. Herein, carbon nanodonuts (CNDs) with a donut-shaped structure are synthesized using sodium alginate (SA) and 1,8-diaminooctane (DAO) through a one-step thermal process. The formation of SA/DAO-CNDs occurs through a crosslinking reaction between SA and DAO, creating amide bonds followed by partial carbonization. In human retinal pigment epithelialcells exposed to H2 O2 or lipopolysaccharide, the SA/DAO-CNDs display a more than fivefold reduction in reactive oxygen species and proinflammatory cytokines, such as IL-6 and IL-1β, when compared to carbonized nanomaterials produced exclusively from SA. Furthermore, the CNDs effectively inhibit vascular endothelial growth factor A-165 (VEGF-A165 )-induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF-A165 , with a dissociation constant of 2.2 × 10-14 M, over 1600 times stronger than the commercial drug bevacizumab (Avastin). Trypsin digestion coupled with LC-MS/MS analysis reveals that VEGF-A165 interacts with SA/DAO-CNDs through its heparin-binding domain, leading to activity loss. The SA/DAO-CNDs demonstrate excellent biocompatibility and potent anti-angiogenic effects in chicken embryos and rabbit eyes. These findings suggest that SA/DAO-CNDs hold promise as a therapeutic agent for treating various angiogenesis-related ocular diseases.

The Fasciola hepatica egg development and hatching test (EDHT) using commercial drugs: a simple protocol for tackling anthelminthic resistance and promoting cattle productivity.

Fasciolosis is an important zoonotic disease caused by the trematode Fasciola hepatica, and it causes great losses in bovine production. The anthelmintic resistance is a major problem in the control of fasciolosis. In this study, the F. hepatica egg development and hatching test (EDHT) was used for the evaluation of the ovicidal activity of commercial drugs, commonly used for treating infected cattle, which reflects F. hepatica anthelminthic resistance in infected bovines, according to recent literature. Bile samples from F. hepatica naturally parasitized cattle were obtained from slaughterhouses in the cities of Lages and Otacílio Costa, Santa Catarina State, Brazil. The bile was washed, the eggs were recovered, quantified, and distributed in universal collectors, with a minimum of 1,000 eggs per vial. Four commercial drugs were used in this study, containing albendazole sulfoxide (ABDZ), closantel (CSTL), nitroxynil (NTXL), and triclabendazole with fenbendazole (TBZF). The drugs were diluted according to the manufacturer instructions. All drugs, and the respective control, were tested in triplicates, with the quantity of recovered eggs determining the number of drugs to be tested. The vials were incubated for 28days at 27°C, and the eggs were classified according to their degree of development under a stereomicroscope. In total, 121 egg samples were analyzed. Two samples were identified as resistant to TBZF. Undetermined resistance/susceptibility has been found in two isolates treated with ABDZ, one treated with NTXL and six treated with TBZF. CSTL did not present ovicidal activity and cannot be used in EDHT. This is the first time that commercial drugs were used in F. hepatica EDHT.

Predicting Autoxidation of Sulfides in Drug-like Molecules Using Quantum Mechanical/Density Functional Theory Methods.

Autoxidation of drugs and drug-like molecules is a major concern in the development of safe and effective therapeutics. Because active pharmaceutical ingredients (APIs) that contain sulfur atoms can form sulfoxides under oxidative stress, predicting oxidative susceptibilities within an organic molecule can have a major impact in accelerating the compound's stability assessment. For investigation of a sulfur atom's oxidative stability, density functional theory (DFT) methods were applied to accurately predict S-O estimated bond dissociation enthalpies (BDEs) of sulfoxides. Our process employed B3LYP/6-31+G(d) for geometry optimization and frequency calculation, and we employed B3P86/6-311++G(2df,2p) to obtain electronic energies from single-point energy calculations. A total of 84 drug-like molecules containing 50 different sulfide scaffolds were used to develop a risk scale. Our results showed that when S-O BDE is less than 69 kcal/mol, the sulfur atom has low oxidative susceptibility. High oxidation risk occurs when the S-O BDE is greater than 75 kcal/mol. The risk scale was successful in predicting the relative propensities of sulfide oxidation among the small organic molecules and commercial drugs examined.

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach.

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.

Design of a Reciprocal Injection Device for Stability Studies of Parenteral Biological Drug Products

Formulation screening, essential for assessing the impact of physical, chemical, and mechanical stresses on protein stability, plays a critical role in biologics drug product development. This research introduces a Reciprocal Injection Device (RID) designed to accelerate formulation screening by probing protein stability under intensified stress conditions within prefilled syringes. This versatile device is designed to accommodate a broad spectrum of injection parameters and diverse syringe dimensions. A commercial drug product was employed as a model monoclonal antibody formulation. Our findings effectively highlight the efficacy of the RID in assessing concentration-dependent protein stability. This device exhibits significant potential to amplify the influences of interfacial interactions, such as those with buffer salts, excipients, air, metals, and silicone oils, commonly found in combination drug products, and to evaluate the protein stability under varied stresses.

N-Tuples on Scaffold Diversity Inspired by Drug Hybridisation to Enhance Drugability: Application to Cytarabine.

A mathematical concept, n-tuples are originally applied to medicinal chemistry, especially with the creation of scaffold diversity inspired by the hybridisation of different commercial drugs with cytarabine, a synthetic arabinonucleoside derived from two marine natural products, spongouridine and spongothymidine. The new methodology explores the virtual chemical-factorial combination of different commercial drugs (immunosuppressant, antibiotic, antiemetic, anti-inflammatory, and anticancer) with the anticancer drug cytarabine. Real chemical combinations were designed and synthesised for 8-duples, obtaining a small representative library of interesting organic molecules to be biologically tested as proof of concept. The synthesised library contains classical molecular properties regarding the Lipinski rules and/or beyond rules of five (bRo5) and is represented by the covalent combination of the anticancer drug cytarabine with ibuprofen, flurbiprofen, folic acid, sulfasalazine, ciprofloxacin, bortezomib, and methotrexate. The insertion of specific nomenclature could be implemented into artificial intelligence algorithms in order to enhance the efficiency of drug-hunting programs. The novel methodology has proven useful for the straightforward synthesis of most of the theoretically proposed duples and, in principle, could be extended to any other central drug.

In‐Vitro Investigation of the α‐Amylase Inhibition Activity of Bare Bis‐Benzylidene‐Cyclohexanone Synthesized by a Highly Selective Solvent‐Free Route

AbstractCurrent work reports the highly selective, solvent‐free synthesis of an endorsed bioactive compound, Bis benzylidine cyclohexanone (BBC) through solid acid catalysed cross aldol condensation route and checks its in‐vitro bio activity. The catalytic support (Multiwalled carbon nanotube) employed was synthesized through the highly sophisticated catalytic chemical vapor deposition (CVD) method and simple mechanical grinding strategy was adopted to decorate sulfonic acid on the support. The C1s X‐ray photoelectron peak of at 290.3 eV confirms the effective interaction of sulfonic acid with MWCNT. The sharp and intense desorption peaks observed at approximately 528.7 °C and 655.15 °C in the TPD analysis unmistakably substantiate the strong acidity of the synthesized system. The alpha amylase inhibition activity of the synthesized compound was calculated to be around 88.5 %, which is in par with the commercial drug as it could inhibit only 96 %. Further, the in‐silico (Docking and Molecular Dynamic Simulation) investigations unveiled a new target site for the compound and this can further be studied in detail to advance the applications in drug design. Detailed scrutiny of various parameters was conducted to validate the bioactivity and pharmaceutical potential of the synthesized compound.

Studies on 2-((2, 4-dihydroxybenzylidene) amino)-3-phenylpropanoic acid include antimicrobial, antidiabetic, antioxidant, anticancer, hemolysis, and theoretical QSAR

Studies show that microorganisms resistant to numerous antibiotics spread infections, lengthen hospital stays, and increase fatalities. Amplification factors increase the demand for innovative drug-resistant disease-fighting chemicals. This research synthesised the chiral L-phenyl alanine condensed with a 2, 4-dihydroxy benzaldehyde Schiff base for biological efficacy investigations such as antimicrobial, antidiabetic, DPPH free radical, MTT assay against HeLa cells and hemolysis studies after the characterization. Derived Schiff base showed good inhibition against K. pneumoniae (G-ve), Staphylococcus aureus (G + ve), and Candida albicans (Fungus) at a 50 μg/mL concentration. Minimum inhibitory concentration report exists in between 35 ppm and 45 ppm. It also exhibited IC50 concentrations between 138 and 265 μg/mL in the remaining biological studies. This study uses molecular docking with the help of mcule, the CLC drug discovery work bench and visual studio applications to justify the derived compound biological activity and used work related proteins such as 1HSK, 1XCW, 3K0K, 3FDN and 3GEY for docking study. The compound showed a good binding affinity score against the targets with negative values. This study covers drug-likeness using Spartan-14 HOMO-LUMO energy levels and Swiss ADME to determine the molecular properties of the chemical structure. Theoretical outcomes are compared with commercial drugs and observed nearby results. Both theoretical outcomes supported the experimental biological activities and were good coincidence. Communicated by Ramaswamy H. Sarma