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Abstract: In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1–18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5–385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors. [Copyright &y& Elsevier]

Abstract Acarbose and voglibose are well-known α -amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for α -amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1–18 for their potential α -amylase inhibitory activity. Structures of synthetic derivatives 1 – 18 were identified by different spectroscopic techniques. All compounds 1–18 (IC 50 = 1.61 ± 0.16 μ M to 2.38 ± 0.09 μ M) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC 50 = 1.46 ± 0.26 μ M). A number of derivatives including 8–12 (IC 50 = 1.68 ± 0.1 μ M to 1.97 ± 0.07 μ M) and 14–16 (IC 50 = 1.61 ± 0.16 μ M to 1.93 ± 0.07 μ M) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of α -amylase enzyme. Graphical abstract Image 1 Highlights • Synthesis of aryl and arylidene substituted pyrazolones 1–18. • Screening of compounds for in vitro α -amylase inhibitory activity. • Limited structure-activity relationship (SAR). • Mechanism of inhibition by kinetic studies. • Assessment of ligand-enzyme binding interactions by in silico study. [ABSTRACT FROM AUTHOR]

Symmetrical and unsymmetrical bis-aryl-α,β-unsaturated ketones were synthesized in moderate to excellent yield by treating cyclohexanone with various aldehydes. Dimethylammonium dimethylcarbamate (DIMCARB) was used as both catalyst and reaction medium for the synthesis of monoarylidenes cycloadduct intermediates, which was further used to produce diarylidene cyclohexanones. All the 34 compounds synthesized were evaluated for their anti-proliferative activity, particularly against promastigote of Leishmania amazonensis , epimastigoteand trypomastigoteof Trypanosoma cruzi . Eighteen compounds displayed anti-leishmanial activity against promastigotes of L . amazonensis with IC 50 values ranging from 2.8 to 10 μM. In addition, two compounds exhibited significant antitrypanosomal activity against epimastigotes of T. cruzi with IC 50 values of 5.2 ± 0.8 and 3.0 ± 0.0 μM, while five compounds exhibited activity from 15.0 ± 1.4 to 30.2 ± 1.8 μM against trypomastigote of T. cruzi . Moreover, all compounds were more selective against the parasites than the epithelial cells. The unsymmetrical compounds 16 , 28 , 30 and 33 can be considered as favorable anti-parasitic lead molecule having IC 50 and EC 50 values in the low-micromolar range, better than the reference drug benznidazole, and low cytotoxicity against Vero cells. The potent compounds were screened in silico against 17 enzymes of T. cruzi and best scoring were found against Dihydroorotate Dehydrogenase. [ABSTRACT FROM AUTHOR]

Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α -amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1 – 45 were synthesized and screened for in vitro α -amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC 50 values of 1.48 ± 0.38–2.99 ± 0.14 μM, when compared to the standard acarbose (IC 50  = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α -amylase enzyme, in silico study was conducted. [ABSTRACT FROM AUTHOR]

In this study synthesis and β -glucuronidase inhibitory potential of 3/5/8 sulfonamide and 8-sulfonate derivatives of quinoline ( 1–40 ) are discussed. Studies reveal that all the synthetic compounds were found to have good inhibitory activity against β -glucuronidase. Nonetheless, compounds 1 , 2 , 5 , 13 , and 22 – 24 having IC 50 values in the range of 1.60–8.40 μ M showed superior activity than the standard saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 μ M). Moreover, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites. Structures of all the synthetic compounds were confirmed through 1 H NMR, EI-MS and HREI-MS spectroscopic techniques. [ABSTRACT FROM AUTHOR]

Acarbose, miglitol, and voglibose are the inhibitors of α -glucosidase enzyme and being clinically used for the management of type-II diabetes mellitus. However, many adverse effects are also associated with them. So, the development of new therapeutic agents is an utmost interest in medicinal chemistry research. Current study is based on the identification of new α -glucosidase inhibitors. For that purpose, hydrazinyl arylthiazole based pyridine derivatives 1–39 were synthesized via two step reaction and fully characterized by spectroscopic techniques EI-MS, HREI-MS, 1 H-, and 13 C NMR. However, stereochemistry of the iminic bond was confirmed by NOESY. All compounds were subjected to in vitro α -glucosidase inhibitory activity and found many folds active (IC 50 = 1.40 ± 0.01–236.10 ± 2.20 μ M) as compared to the standard acarbose having IC 50 value of 856.45 ± 5.60 μ M. A limited structure-activity relationship was carried out in order to make a presumption about the substituent's effect on inhibitory activity which predicted that substituents of more negative inductive effect played important role in the activity as compared to the substituents of less negative inductive effect. However, in order to have a good understanding of ligand enzyme interactions, molecular docking study was also conducted. In silico study was confirmed that substituents like halogens (Cl) and nitro (NO 2 ) which have negative inductive effect were found to make important interactions with active site residues. [ABSTRACT FROM AUTHOR]

Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1 H -imidazol-1-yl)ethyl aryl carboxylate derivatives 1–26 , by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1′-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, 1 H -NMR and 13 C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β -glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC 50 = 1.20 ± 0.01–60.30 ± 1.40 μ M as compared to the standard d -saccharic acid 1,4-lactone (IC 50 = 48.38 ± 1.05 μ M). Compounds 1 , 3 , 4 , 6 , 9 – 19 , and 21 – 24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO 2 , F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies. [ABSTRACT FROM AUTHOR]

3-Thiazolylcoumarin derivatives 1–14 were synthesized via one-pot two step reactions, and screened for in vitro α -glucosidase inhibitory activity. All compounds showed inhibitory activity in the range of IC 50 = 0.12 ± 0.01–16.20 ± 0.23 μ M as compared to standard acarbose (IC 50 = 38.25 ± 0.12 μ M), and also found to be nontoxic. Molecular docking study was carried out in order to establish the structure-activity relationship (SAR) which demonstrated that electron rich centers at one and electron withdrawing centers at the other end of the molecules showed strong inhibitory activity. All the synthesized compounds were characterized by spectroscopic techniques such as EI-MS, HREI-MS, 1 H NMR and 13 C NMR. CHN analysis was also performed. [ABSTRACT FROM AUTHOR]

Abstract: New series of 4,5-disubstituted-2,4-dihydro-3H-1,2,4-triazole-3-thiones (8a–j) and 2,5-disubstituted-1,3,4-thiadiazoles (9a–h) were synthesized by dehydrative cyclization of hydrazinecarbothioamide derivatives (7a–k) by refluxing in 4N aqueous sodium hydroxide and by overnight stirring with polyphosphoric acid, respectively. The structures of the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR, elemental analysis and mass spectroscopic studies and the synthesized compounds were screened for their antioxidant and urease inhibition activities. N-(2,4-Dimethylphenyl)-5-(4-nitrophenyl)-1,3,4-thiadiazol-2-amine (9h) showed excellent antioxidant activity more than the standard drug whereas 4-(2,4-dimethylphenyl)-5-(3-nitrophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (8d) and 4-(2,3-dimethylphenyl)-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (8e) exhibited potent urease inhibitory activities. [ABSTRACT FROM AUTHOR]

Benzotriazoles (4–6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7–40). The synthetic compounds (7–40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for α -glucosidase and α -amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC 50 values of 2.00–5.6 and 2.04–5.72 μ M against α -glucosidase and α -amylase enzymes, respectively. The synthetic compounds were divided into two categories "A" and "B" , in order to understand the structure-activity relationship. Compounds 25 (IC 50 = 2.41 ± 1.31 μ M), (IC 50 = 2.5 ± 1.21 μ M), 36 (IC 50 = 2.12 ± 1.35 μ M), (IC 50 = 2.21 ± 1.08 μ M), and 37 (IC 50 = 2.00 ± 1.22 μ M), (IC 50 = 2.04 ± 1.4 μ M) with chloro substitution/s at aryl ring were found to be most active against α -glucosidase and α -amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against α -amylase and non-competitive mode of inhibition against α -glucosidase enzyme. Image 1 • Benzotriazoles (1–40) were synthesized. • The synthetic molecules were screened for α -glucosidase and α -amylase inhibitory activity. • The synthetic molecules were divided into two categories to understand the better structure-activity relationship. • In silico studies were performed to confirm the binding interactions of synthetic molecules with the enzyme active site. • Kinetic studies determined the mechanism of action of both enzymes. [ABSTRACT FROM AUTHOR]