Acid Derivatives Research Articles

Bioisosteric replacement of the carboxylic acid group in Hepatitis-C virus NS5B thumb site II inhibitors: phenylalanine derivatives

Hepatitis C virus (HCV) is a global health concern and the NS5B RNA-dependent RNA polymerase (RdRp) of HCV is an attractive target for drug discovery due to its role in viral replication. This study focuses on NS5B thumb site II inhibitors, specifically phenylalanine derivatives, and explores bioisosteric replacement and prodrug strategies to overcome limitations associated with carboxylic acid functionality. The synthesized compounds demonstrated antiviral activity, with compound 6d showing the most potent activity with an EC50 value of 3.717 μM. The hydroxamidine derivatives 7a-d showed EC50 values ranging from 3.9 μM to 11.3 μM. However, the acidic heterocyclic derivatives containing the oxadiazolone (8a-d) and oxadiazolethione (9a-d) rings did not exhibit measurable activity. A methylated heterocycle 10b showed a hint of activity at 8.09 μM. The pivaloyloxymethyl derivatives 11a and 11b did not show antiviral activity. Further studies are warranted to fully understand the effects of these modifications and to explore additional strategies for developing novel therapeutic options for HCV.

Molecular Modeling Studies to Mimic the Binding Hypothesis of NEU3 Sialidase and EGFR in Nonsmall Cell Lung Carcinoma

The activation of the Neuraminidase 3 (NEU3) enzyme has been associated with the hyperphosphoryla-tion of Epidermal Growth Factor Receptor (EGFR) in Nonsmall Cell Lung Carcinoma (NSCLC). Existing EGFR inhibitors (such as gefitinib, erlotinib, lapatinib, icotinib, afatinib and osimertinib) reduce the hyperactivation of downstream signaling pathways (Akt, Mapk, Jak-Stat, Plc) but fail to completely abolish EGFR hyperphosphorylation. Therefore, co-targeting NEU3 and EGFR presents a greater potential to be used as a combinatorial therapy for NSCLC. This study employs structure guided approaches to elucidate the binding hypothesis of NEU3 and EGFR inhibitors. Toward this, important 3D features associated with high inhibitory potency of NEU3, and EGFR modulators were identified through SAR. The triazole substitution in acetamide dihydropyran carboxylic acid derivatives is mainly responsible for improved inhibitory potency against NEU3. Therefore, the hydrophobic ([Formula: see text]-H) interaction with the benzene ring and hydrogen bonding with the hydroxyl group of triazole are critical for designing new NEU3 modulators. Molecular Dynamics (MD) simulation studies demonstrate the stability of hydrogen bonding interactions of highly active NEU3 inhibitors with Pro66, Gly199 and Glu410 residues. Similarly, pyrimidine ring of EGFR inhibitors forms stable hydrogen bonds with Lys721 and Asp831 residues, contributing to their inhibitory potency. Our findings suggest that incorporating these identified 3D features associated with triazole and pyrimidine substitutions into a suitable scaffold could be a valuable strategy for developing a new generation of NEU3 and EGFR modulators. This approach offers a potential multi-targeted therapy for NSCLC patients.

Epinephrine, Pregabalin, and Crizotinib as Three Medicines with Polish Implications over Three Last Centuries and in View of Three Different Drug Discovery Approaches.

The discovery of epinephrine (adrenaline) and its subsequent implications in medicine owes significant contributions to Cybulski across different centuries, who, in 1894, was pivotal in identifying the adrenal medulla's role in blood pressure regulation and naming the active substance "nadnerczyna", known today as adrenaline. His work demonstrated the adrenal glands' critical function in the body's regulatory mechanisms beyond the nervous system. Cybulski's groundbreaking research laid foundational knowledge for future endocrinological studies and pharmaceutical advancements. In the late 20th century, Andruszkiewicz collaborated with Silverman at Northwestern University to develop pregabalin, the active ingredient in Lyrica. Their innovative synthesis of gamma-aminobutyric acid derivatives led to a significant advancement in treating epilepsy, neuropathic pain, and fibromyalgia. Andruszkiewicz's expertise in organic chemistry and enzymology was crucial in this collaborative effort, resulting in the successful development and commercialization of Lyrica. Additionally, Mroczkowski's leadership at Pfizer contributed to the development of crizotinib, a notable anaplastic lymphoma kinase and proto-oncogene 1 tyrosine-protein kinase inhibitor used to treat specific types of non-small cell lung cancer. Her work exemplifies the continuing influence of Polish researchers in pioneering drug discovery and advancing therapeutic treatments over the past three centuries. These contributions highlight Poland's significant role in global pharmaceutical innovations and medical research.

Structural Optimization and Structure-Activity Relationship of 1H-Pyrazole-4-carboxylic Acid Derivatives as DNA 6mA Demethylase ALKBH1 Inhibitors and Their Antigastric Cancer Activity.

DNA N6-methyladenine (6mA) demethylase ALKBH1 plays an important role in various cellular processes. Dysregulation of ALKBH1 is associated with the development of some cancer types, including gastric cancer, implicating a potential therapeutic target. However, there is still a lack of potent ALKBH1 inhibitors. Herein, we report the discovery of a highly potent ALKBH1 inhibitor, 1H-pyrazole-4-carboxylic acid derivative 29. The structure-activity relationship of this series of compounds was also discussed. Because of the poor cell membrane permeability of 29, we prepared a prodrug of 29 (29E), which showed excellent cellular activities. In gastric cancer cell lines HGC27 and AGS, 29E treatment significantly increased the abundance of 6mA, inhibited cell viability, and upregulated the AMP-activated protein kinase (AMPK) signaling pathway. In addition, the hydrolysis product 29 showed high exposure in mice after administration of 29E. Collectively, this research provides a new potent ALKBH1 inhibitor, which could serve as a lead compound for subsequent drug development.

Stereoselective Synthesis of α‐Azido Esters and α‐Amino Acid Derivatives via Matteson Homologation of Boronic Esters

AbstractMatteson homologation with sodium azide in DMF proved to be an excellent highly stereoselective tool for the synthesis of complex α‐azido and α‐amino acids. Both enantiomers are easily accessible via the choice of the chiral boronic ester auxiliary.

Asymmetric Catalytic Synthesis of Allylic Sulfenamides from Vinyl α‐Diazo Compounds by a Rearrangement Route

The asymmetric rearrangement of allylic sulfilimines is an effective route to synthetic attractive targets such as allylic sulfenamides and others. The current methods are limited to chirality transfer from chiral allylic sulfilimine precursors. Herein, we report a general and fundamentally new rearrangement route accessing optically enriched allylic sulfenamides and their derivatives. The process involves a S‐alkylation and an unusual S‐to‐N rearrangement step. The chiral nickel complex enables the transformation of a broad scope of sulfenamides and vinyl α‐diazo pyrazoleamides under mild conditions. Various allylic sulfenamides have been synthesized with excellent γ‐regioselectivity and enantioselectivity, which can be efficiently converted to sulfinamide and 4‐aminobutenoic acid derivatives. In addition, DFT calculations demonstrate the connection between the spin state and conformation of nickel vinyl carbenoid, as well as an unknown rearrangement process.

Prediction of Flavor Potential of Ocimum basilicum L. Side-Stream Phytoconstituents, Using Liquid Chromatography–Tandem Mass Spectrometry Analysis and In Silico Techniques

Although post-distillation side-streams of basil (Ocimum basilicum L.) pose significant economic and environmental challenges, they also bring forth new opportunities in the flavor industry. Thus, the objective of the current study was to assess the phenolic profile of basil side-stream extracts to identify key compounds and to evaluate their taste properties, using liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis, flavor prediction tools and molecular docking. In particular, 52 phytoconstituents, mainly phenolic acids, salvianolic acids, flavonoids and fatty acids derivatives, were elucidated in the side-streams of two different basil varieties (Minimum and Genovese) harvested and distilled in early and late autumn, highlighting the effect of pre-harvest factors on basil’s phenolic fingerprint. Furthermore, the results of tests undertaken using taste prediction tools showed that most of the identified compounds were very likely to taste bitter, while six of them (caffeoylferuloyltartaric acid, isoquercetin, lithospermic acid A, sagerinic acid, salvianolic acids C and F) presented a high bitterant capacity (70–90%). Moreover, according to molecular docking studies, these compounds exhibited a stronger binding affinity to the hTAS2R46 bitter receptor compared to its known agonist, strychnine. This outcome and consequently their bitterness were mainly attributed to interactions with Glu265, Thr180 and/or Trp88 through the formation of direct hydrogen bonds. Therefore, the present results provide insights into the taste profiles of basil side-streams, leading to more sustainable and innovative uses of aromatic herbs residues.

3D-Printed Phenylboronic Acid-Bearing Hydrogels for Glucose-Triggered Drug Release.

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome via personalized therapy. Therein, 3D-printed phenylboronic acid-containing implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result is a sub-centimeter scaled 3D-printed bioinert implant that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemic to hyperglycemic levels readily allow the release of pinacol, i.e., a 1,2-diol-containing model molecule, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage.

Asymmetric Catalytic Synthesis of Allylic Sulfenamides from Vinyl α-Diazo Compounds by a Rearrangement Route.

The asymmetric rearrangement of allylic sulfilimines is an effective route to synthetic attractive targets such as allylic sulfenamides and others. The current methods are limited to chirality transfer from chiral allylic sulfilimine precursors. Herein, we report a general and fundamentally new rearrangement route accessing optically enriched allylic sulfenamides and their derivatives. The process involves a S-alkylation and an unusual S-to-N rearrangement step. The chiral nickel complex enables the transformation of a broad scope of sulfenamides and vinyl α-diazo pyrazoleamides under mild conditions. Various allylic sulfenamides have been synthesized with excellent γ-regioselectivity and enantioselectivity, which can be efficiently converted to sulfinamide and 4-aminobutenoic acid derivatives. In addition, DFT calculations demonstrate the connection between the spin state and conformation of nickel vinyl carbenoid, as well as an unknown rearrangement process.

Anti-neoplastic Properties of Boswellic Acids and their Novel Semi-synthetic Analogs: In vitro, In vivo and Clinical Evidence

Introduction: Recently, Boswellia gum resin extract has been shown to exhibit therapeutic properties against multiple inflammatory illnesses, comprising arthritis, asthma, diabetes, inflammatory bowel disease, and different malignancies. There are growing shreds of evidence that Boswellia extracts and their phytoconstituents could be used in adjuvant and combinatorial chemotherapeutic approaches for the management and prevention of cancer. Aim: The principal objective of this comprehensive investigation is to offer up-to-date and in-depth insights into the anticancer potential of boswellic acids along with their semisynthetic analog that are novel and preventive/therapeutic substitutes for the management of cancer and inflammatory diseases due to their strong potential. Materials and Methods: In the course of this review, a comprehensive compilation of In-vitro, Invivo, and clinical evidence on the antineoplastic potential of boswellic acids was assembled through systematic computerized searches utilizing platforms such as Google Scholar, PubMed, Sci-Hub, and Research Gate. Result: Boswellic acids, the key compounds found in the resin of nearly all the species of the Boswellia plant, have been reported to exhibit therapeutic effects by modulating various targets in different disease conditions. Moreover, semisynthetic derivatives of boswellic acids show strong cytotoxic effects, particularly those with cyanoenone moieties, endoperoxides, and hybrids, which exhibit enhanced potency. Conclusion: In this review, we have sincerely highlighted the effectiveness of novel boswellic acids as alternative preventive and therapeutic agents for the treatment of cancer and inflammatory conditions. Their strong anticancer potential could provide a basis for promising future direction to develop potent anticancer drugs for human malignancies.

UHPLC-MS/MS chemical profiling, preliminary toxicity, in vitro antioxidant potential and antimicrobial activity of Brachyotum naudinii Triana flowers

Chemical compounds of Brachyotum naudinii Triana flowers were analyzed using UHPLC-MS/MS. Anthocyanin dry extract was obtained by accelerated solvent extraction with 70% ethanol acidified with citric acid (pH 3.18) and then spray dried. Preliminary toxicity of anthocyanin extract was evaluated using Artemia salina Leach, while its antioxidant capacity was measured by DPPH• and ABTS•+ methods, and reducing capacity was assessed using FRAP assay. Results showed the flowers comprise 39% tannins, 21% flavonol glycosides, 14% organic acids, 11% anthocyanins, 7% coumaric acid derivatives, 4% polar lipids, and 4% disaccharides. Anthocyanin extract exhibited moderate toxicity against Artemia salina (LC50 = 106.9 ± 9.9 µg mL−1) and showed inhibitory effects on DPPH• and ABTS•+ radicals, as well as reducing capacity in FRAP assay, though statistically different from Trolox (p < 0.05). The flowers have demonstrated antimicrobial activity against Staphylococcus aureus and are a source of novel anthocyanin compounds with antioxidant potential.

UPLC-MS/MS and HS-SPME-GC–MS reveal the flavor profiles of two geographical indications woody vegetables: Staphylea bumalda and Staphylea holocarpa

Staphylea bumalda (SHC) and Staphylea holocarpa (PGG) were recognized as geographical indication agricultural products due to unique flavor. 1218 differential non-volatile compounds and 536 differential volatile compounds were detected and identified through UPLC-MS/MS and HS-SPME-GC–MS methods. In SHC samples, catechins, epicatechins, proanthocyanidins, quinic acid derivatives, and kaempferol glycoside derivatives were the main flavor compounds, with bitter and harsh taste. L-tartaric acid, citraconic acid and citric acid were contributed to increase acidity. 4-Hexen-1-ol acetate, butanoic acid butyl ester, 3-Hexen-1-ol acetate, (E)-, and 3-Hexen-1-ol acetate, (Z)- were identified as characteristic odor compounds with strong floral, fruity and sweet odor. In PGG samples, epicatechin gallate, quercetin glycoside derivatives, L-histidine, and L-tyrosine were the leading contributors to bitter and harsh taste. The spicy, herbal, and bad smell odor were mainly brought by 2-octanol, and 3-Octen-1-ol, (Z)-. Our results offered comprehensive insights into the flavor and quality characteristics differences between PGG and SHC.

Ectoin attenuates cortisone-induced skin issues by suppression GR signaling and the UVB-induced overexpression of 11β-HSD1.

Accelerated pace of modern work and lifestyles subject individuals to various external and psychological stressors, which, in turn, can trigger additional stress through visible signs of fatigue, hair loss, and obesity. As the primary stress hormone affecting skin health, cortisol connects to the glucocorticoid receptor (GR) to aggravate skin issues induced by stress. This activation depends on the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in skin cells, which locally converts cortisone-produced by the central and peripheral hypothalamic-pituitary-adrenal axis-into its active form. Our study delves deeper into stress's adverse effects on the skin, including the disruption of keratinocyte structural proteins, the loss of basement membrane proteins, and the degradation of collagen. Remarkably, we discovered that Ectoin, an amino acid derivative obtained from halophilic bacteria, is capable of mitigating the inhibitory impacts of cortisone on the expression of cutaneous functional proteins, including involucrin, loricrin, laminin-5, and claudin-1. Moreover, Ectoin reduces the suppressive effect of stress on collagen and hyaluronic acid synthesis by impeding GR signal transduction. Additionally, Ectoin counterbalances the UVB-induced overexpression of 11β-HSD1, thereby diminishing the concentration of endogenous glucocorticoids. Our findings illuminate the significant potential of Ectoin as a preventative agent against stress-induced skin maladies.

The synthesis of novel unnatural amino acid by intramolecular aza-Michael addition reaction as multitarget enzyme inhibitors.

Synthesis of novel unnatural amino acids (UAAs) from 4-oxo-4-phenylbut-2-enoic acid derivatives with intramolecular aza-Michael addition reaction in the presence of chlorosulfonyl isocyanate (CSI) was reported in soft conditions without any metal catalyst. Acids and base as a catalyst, and solvents effects were investigated for the synthesis of novel UAAs. This novel method provides inexpensive, practicable, and efficient approach to generate UAAs. The use of UAAs has attracted great interest in the development of therapeutic agents and drug discovery to improve their properties. In this context, in addition to the synthesis of new UAAs, their inhibition effects on important metabolic enzymes of acetylcholinesterase (AChE) and carbonic anhydrases I and II (hCA I and II) enzymes were investigated. The compound 2g showed the best inhibition for CA I and AChE enzymes, while compound 2i exhibited the best inhibition profile against CA II isoenzyme. The inhibition values of these compounds were found as 1.85 ± 0.64 for AChE, 0.53 ± 0.07 for hCA I, 0.44 ± 0.15 µM for hCA II, respectively, and they showed a stronger inhibitory property than acetazolamide (standard inhibitor for hCA I and II) and tacrine (standard inhibitor for AChE) molecules. The activity of the studied molecule against different proteins that are hCA I (PDB ID: 2CAB), hCA II (PDB ID: 5AML), and AChE (PDB ID: 1OCE) was examined. Finally, the drug properties of the studied molecule were examined by performing absorption, distribution, metabolism, excretion, and toxicity analysis.

A Systematic Review of Medicinal Plants and Their Compounds Validated as Agents for the Management of Sickle Cell Disease

Some plants used in traditional medicine to manage sickle cell disease have been validated pharmacologically to ascertain their anti-sickling properties. However, there is no global systematic review of the evidence in support of their use for sickle cell management. This research aimed to conduct a systematic review of the pharmacological evidence to highlight species, genera, and some phytochemicals which could be primed for novel anti-sickling medications. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were used. Articles in English, published from 2000 to 2022 were included in the analysis. The literature search covered 411 publications of which 82 were found to be eligible. More than half (53.65%) of the articles were published from 2016 to 2022. Anti-sickling research from Africa accounted for 86.58% of the publications, with more than half coming from Nigeria, 12.20% from Asia and only 1.22% from Europe. The Fabaceae, Euphorbiaceae, and Annonaceae were the top three plant families whereas Zanthoxylum and Terminalia were the most reported genera. Carica papaya and Terminalia catappa were the most reported species. Sickling reversal ( n = 33/82) and hemoglobin polymerization studies ( n = 29/82) were the most reported assays. Benzoic acid derivatives, butyl stearate, ellagic acid derivatives, and some pentacyclic triterpenoids were the only plant derived compounds validated for anti-sickling activities. A total of 117 plant species with anti-sickling activities were documented. Studies on secondary metabolites with anti-sickling properties to serve as scaffolds for novel drug development for sickle cell management were limited.

Effect of weaning strategies on biosynthesis of oxylipids in Holstein dairy calves

The aim of this study was to determine the effect of the weaning calves at 2 ages (early vs. late) and 2 weaning paces (abrupt over 3 d vs. gradual over 14 d) on plasma oxylipids. Seventy-one dairy calves (38.8 ± 4.4 kg, body weight ± standard deviation), blocked by sex and body weight at birth, were randomly assigned in a 2 × 2 factorial arrangement of treatments. The factors were weaning age (early (6–7 weeks) vs. late (8–9 weeks)), and weaning pace (abrupt (3 weaning steps over 2 d) vs. gradual (7 weaning steps over 14 d)), generating 4 treatment groups: early-abrupt, early-gradual, late-abrupt, and late-gradual. Blood samples were collected from the jugular vein one day pre-weaning, and one day post-weaning. Oxylipids concentration was measured by liquid chromatography-tandem mass spectrometry. Fatty acid profile (including nonesterified fatty acids) was also assessed. Weaning pace, age, pace × age, body weight at birth, and sex were included as fixed effect and cohort was included as random effect in the model. Linoleic acid derivatives 13- oxooctadecadienoic (OxoODE) and 9-OxoODE had a greater concentration in calves abruptly weaned when compared with that for gradually weaned calves. Calves weaned gradually showed a greater concentration of 9- hydroxyoctadecadienoic (HODE), 13-HODE, 12,13- dihydroxyoctadecenoic (DiHOME), 9,10-DiHOME, all linoleic acid-derived compared with that for abruptly weaned calves. Anti-inflammatory oxylipid 17,18- dihydroxyeicosatrienoic (DiHETE), an eicosapentaenoic acid (EPA) derivative, was greater in calves abruptly weaned compared with gradual. Overall, pace of weaning affected the plasma concentration of oxylipids, demonstrating that weaning pace affects the oxylipids status involved in inflammation in dairy calves.

Structural and quantitative comparison of viral infection-associated N-glycans in plasma from humans, pigs, and chickens: Greater similarity between humans and chickens than pigs

Host N-glycans play an essential role in the attachment, invasion, and infection processes of viruses, including zoonotic infectious diseases. The similarity of N-glycans in the trachea and lungs of humans and pigs facilitates the cross-species transmission of influenza viruses through respiratory tracts. In this study, the structure and quantity of N-glycans in the plasma of humans, pigs, and chickens were analyzed using liquid chromatography-quadrupole-Orbitrap-tandem mass spectrometry. N-glycans in humans (35), pigs (28), and chickens (53) were identified, including the most abundant, species-common, and species-specific N-glycans. Among the N-glycans (relative quantity >0.5%), the sialic acid derivative of N-acetylneuraminic acid was identified in humans (the sum of the relative quantities of each; 64.3%), pigs (45.5%), and chickens (64.4%), whereas N-glycolylneuraminic acid was only identified in pigs (18.1%). Sialylated N-glycan linkage isomers are the influenza virus receptors (α2-6 in humans, α2-3 and α2-6 in pigs, and α2-3 in chickens). Only α2-6 linkages (human, 58.2%; pig, 44.8%; and chicken, 60.6%) were more abundant than α2-3/α2-6 linkages (human, 4.6%; pig, 0.6%; and chicken, 3.4%) and only α2-3 linkages (human, 1.5%; pig, 0.1%; and chicken, 0.4%). Fucosylation, which can promote viral infection through immune modulation, was more abundant in pigs (76.1%) than in humans (36.4%) and chickens (16.7%). Bisecting N-acetylglucosamine, which can suppress viral infection by inhibiting sialylation, was identified in humans (10.3%) and chickens (16.9%), but not in pigs. These results indicate that plasma N-glycans are similar in humans and chickens. This is the first study to compare plasma N-glycans in humans, pigs, and chickens.

Exploring the Potential of Isoindole‐1,3‐Dione Derivatives as Novel Inhibitors of Aldose Reductase: An In Silico and In Vitro Insight into Therapeutic Strategies for Diabetic Complications

AbstractThis study explores the potential of isoindole‐1,3‐dione derivatives as novel inhibitors of aldose reductase (AR), focusing on their in silico and in vitro effects for therapeutic strategies against diabetic complications. Aldose reductase, a critical enzyme in the polyol pathway, plays a significant role in glucose metabolism and has been linked to diabetic complications. In this comprehensive study, isoindole‐1,3‐dione derivatives were synthesized and evaluated for their inhibitory effects on the recombinant human AR enzyme. The compounds’ inhibitory activities were measured both in vitro and through in silico techniques, employing molecular docking and free binding energy calculations and ADME studies. The newly synthesized compounds demonstrated varied inhibitory effects, with ethyl and phenyl substituents at specific positions enhancing inhibitory activity. Notably, compounds with carboxylic acid derivatives exhibited potent inhibitory effects, especially compound 6 with an IC50 value of 1.649 μM. In conclusion, this study provides valuable insights into the inhibitory potential of isoindole‐1,3‐dione derivatives against AR, suggesting their potential therapeutic application in mitigating diabetic complications. The combination of experimental and computational approaches offers a comprehensive understanding of the compounds’ interaction mechanisms and pharmacokinetic profiles, supporting their further exploration as antidiabetic agents.

Combining chemical profiles and biological abilities of different extracts from Tanacetum nitens(Boiss. & Noë)Grierson using network pharmacology.

Tanacetum nitens(Boiss. & Noë)Grierson is an aromatic perennial herb used in Turkish traditional medicine to treat headache, fever, and skin diseases. This study aimed to investigate the chemical composition, antioxidant, enzyme inhibition, and cytotoxic properties of T. nitens aerial parts. Organic solvent extracts were prepared by sequential maceration in hexane, dichloromethane, ethyl acetate, and methanol while aqueous extracts were obtained by maceration or infusion. Nuclear magnetic resonance (NMR) and LC-DAD-MS analysis allowed the identification and quantification of different phytoconstituents including parthenolide, tanacetol B, tatridin B, quinic acid derivatives, β-sitosterol, and glycoside derivatives of quercetin and luteolin. The type and amount of these phytochemicals recovered by each solvent were variable and significant enough to impact the biological activities of the plant. Methanolic and aqueous extracts displayed the highest scavenging and ions-reducing properties while the dichloromethane and ethyl acetate extracts exerted the best total antioxidant activity and metal chelating power. Results of enzyme inhibition activity showed that the hexane, ethyl acetate, and dichloromethane extracts had comparable anti-acetylcholinesterase activity and the latter extract revealed the highest anti-butyrylcholinesterase activity. The best α-amylase and α-glucosidase inhibition activities were obtained from the hexane extract. The dichloromethane and ethyl acetate extracts exhibited the highest cytotoxic effect against the prostate carcinoma DU-145 cells. In conclusion, these findings indicated that T. nitens can be a promising source of biomolecules with potential therapeutic applications.

The Intra- and Intermolecular Friedel-Crafts Acylation of Amino Acid Derivatives in Stereo-retarded Manner

: The Friedel-Crafts acylation of natural or unnatural amino acids in stereoretarded manner is willing to prescribed here. Depending on its main skeleton, the typical intra- and intermolecular Friedel-Crafts reaction of amino acids can be differentiated. The unique amino acid’s general structure can contribute to the reaction between its carboxyl group and the side chain. Depending on the Friedel-Crafts reaction condition, the amino acid’s optical retention can be retarded. This perspective can contribute to the development of this one-century reaction in the field of organic chemistry.