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Synthetic routes to a series of benzoylarylbenzimidazol 3a-h have been derived from 3,4-diaminobenzophenone and an appropriate arylaldehyde in the presence of ammonium chloride or a mixture of ammonium chloride and sodium metabisulfite as catalyst. The antioxidant activity of targeted compounds 3a-h has been measured by four different methods and the overall antioxidant evaluation of the compounds indicated the significant MCA, FRAP, and (DPPH-SA) of the compounds except for the compound 3h. In vitro antidiabetic assay of α-amylase and α-glucosidase suggest a good to excellent activity for most tested compounds. The target benzimidazole 3f containing hydroxyl motif at para-position of phenyl revealed an important activity inhibitor against α- amylase (IC 50  = 12.09 ± 0.38 µM) and α-glucosidase (IC 50  = 11.02 ± 0.04 µM) comparable to the reference drug acarbose. The results of the anti hyperglycemic activity were supported by means of in silico molecular docking calculations showing strong binding affinity of compounds 3a-h with human pancreatic α-amylase (HPA) and human lysosomal acid-α-glucosidase (HLAG) active sites that confirm a good to excellent activity for most of tested compounds., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A series of nineteen (1-19) indole-based-thiadiazole derivatives were synthesized, characterized by 1 HNMR, 13 C NMR, MS, and screened for α-glucosidase inhibition. All analogs showed varied α-glucosidase inhibitory potential with IC 50 value ranged between 0.95 ± 0.05 to 13.60 ± 0.30 µM, when compared with the standard acarbose (IC 50  = 1.70 ± 0.10). Analogs 17, 2, 1, 9, 7, 3, 15, 10, 16, and 14 with IC 50 values 0.95 ± 0.05, 1.10 ± 0.10, 1.30 ± 0.10, 1.60 ± 0.10, 2.30 ± 0.10, 2.30 ± 0.10, 2.80 ± 0.10, 4.10 ± 0.20 and 4.80 ± 0.20 µM respectively showed highest α-glucosidase inhibition. All other analogs also exhibit excellent inhibitory potential. Structure activity relationships have been established for all compounds primarily based on substitution pattern on the phenyl ring. Through molecular docking study, binding interactions of the most active compounds were confirmed. We further studied the kinetics study of analogs 1, 2, 9 and 17 and found that they are Non-competitive inhibitors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC 50  = 23.08 ± 0.03 µM), (IC 50  = 26.08 ± 0.43 µM), 5 (IC 50  = 24.57 ± 0.07 µM), (IC 50  = 27.57 ± 0.07 µM), 6 (IC 50  = 24.94 ± 0.12 µM), (IC 50  = 27.13 ± 0.08 µM), 16 (IC 50  = 27.57 ± 0.07 µM), (IC 50  = 29.13 ± 0.18 µM), and 28 (IC 50  = 26.94 ± 0.12 µM) (IC 50  = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Thirty benzofuran-2-yl(phenyl)methanones 1-30 were synthesized and characterized their structures by spectroscopic techniques. Substituted phenacyl bromide and different derivatives of 2-hydroxy-benzaldehyde treated in the presence of anhydrous K 2 CO 3 in acetonitrile at room temperature to afford the desired benzofurans 1-30. All compounds were screened for their in vitro α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. Results revealed that para substituted compounds were found to be more active than the others with IC 50 values ranges for α-amylase inhibition (IC 50  = 18.04-48.33 µM), DPPH (IC 50  = 16.04-32.33 µM) and ABTS (IC 50  = 16.99-33.01 µM) radical scavenging activities. Activities results were compared with the standards acarbose (IC 50  = 16.08 ± 0.07 µM) for α-amylase, ascorbic acid (IC 50  = 15.08 ± 0.03 and 15.09 ± 0.17 µM) for DPPH and ABTS radical scavenging activities, respectively. Kinetic studies predicted that all compounds followed non-competitive mechanism of inhibition. Molecular docking results showed good protein-ligand interactions profile against the corresponding target. To the best of our knowledge, out of thirty molecules, ten compounds 18-20, 22, and 25-30 were structurally new., (Copyright © 2020 Elsevier Inc. All rights reserved.)

(E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1-27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against α-amylase and α-glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14-17, 19, and 21-25 are structurally new. All compounds exhibited good to moderate inhibitory potential in terms of IC 50 values ranging (IC 50  = 13.02 ± 0.04-46.90 ± 0.05 µM) and (IC 50  = 13.09 ± 0.08-46.44 ± 0.24 µM) in comparison to standard acarbose (IC 50  = 12.94 ± 0.27 µM and 10.95 ± 0.08 µM), for α-amylase and α-glucosidase, respectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active α-amylase and α-glucosidase inhibitors 5, 7, 9, 15, 24, and 27, suggested non-competitive and competitive types of inhibition mechanism for α-amylase and α-glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H-<, <-<, and <-H etc., against the corresponding targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dihydropyridine derivatives 1-31 were synthesized via one-pot solvent free condition and screened for in vitro against α-amylase and α-glucosidase enzyme. The synthetic derivatives 1-31 showed good α-amylase inhibition in the range of IC 50  = 2.21 ± 0.06-9.97 ± 0.08 µM, as compared to the standard drug acarbose (IC 50  = 2.01 ± 0.1 µM) and α-glucosidase inhibition in the range of IC 50  = 2.31 ± 0.09-9.9 ± 0.1 µM as compared to standard acarbose (IC 50  = 2.07 ± 0.1 µM), respectively. To determine the mode of binding interactions of synthetic molecules with active sites of enzyme, molecular docking studies were also performed. Different spectroscopic techniques such as 1 H, 13 C NMR, EI-MS, and HREI-MS were used to characterize all the synthetic compounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1 H, 13 C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC 50  = 1.23 ± 0.06-4.5 ± 0.03 µM) as compared to the standard acarbose (IC 50 1.20 ± 0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC 50 2.01 ± 0.13-5.3 ± 0.11) and ABTS (IC 50  = 2.34 ± 0.07-5.5 ± 0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC 50  = 1.99 ± 0.09 µM, and IC 50 2.03 ± 0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The current study describes the discovery of novel inhibitors of α-glucosidase and α-amylase enzymes. For that purpose, new hybrid analogs of N-hydrazinecarbothioamide substituted indazoles 4-18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1 H-, and 13 C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4-18 with their intermediates 1-3, were evaluated for in vitro α-glucosidase and α-amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02-4.89 ± 0.02 µM for α-glucosidase and for α-amylase 1.42 ± 0.04-4.5 ± 0.18 µM in comparison with the standard acarbose (IC 50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Novel derivatives of flurbiprofen 1-18 including flurbiprofen hydrazide 1, substituted aroyl hydrazides 2-9, 2-mercapto oxadiazole derivative 10, phenacyl substituted 2-mercapto oxadiazole derivatives 11-15, and benzyl substituted 2-mercapto oxadiazole derivatives 16-18 were synthesized and characterized by EI-MS, 1 H and 13 C NMR spectroscopic techniques. All derivatives 1-18 were screened for α-amylase inhibitory activity and demonstrated a varying degree of potential ranging from IC 50  = 1.04 ± 0.3 to 2.41 ± 0.09 µM as compared to the standard acarbose (IC 50  = 0.9 ± 0.04 µM). Out of eighteen compounds, derivatives 2 (IC 50  = 1.69 ± 0.1 µM), 3 (IC 50  = 1.04 ± 0.3 µM), 9 (IC 50  = 1.25 ± 1.05 µM), and 13 (IC 50  = 1.6 ± 0.18 µM) found to be excellent inhibitors while rest of the compounds demonstrated comparable inhibition potential. A limited structure-activity relationship (SAR) was established by looking at the varying structural features of the library. In addition to that, in silico study was conducted to understand the binding interactions of the compounds (ligands) with the active site of α-amylase enzyme., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In search of potent α-amylase inhibitor we have synthesized eighteen indole analogs (1-18), characterized by NMR and HR-EIMS and screened for α-amylase inhibitory activity. All analogs exhibited a variable degree of α-amylase inhibition with IC 50 values ranging between 2.031 ± 0.11 and 2.633 ± 0.05 μM when compared with standard acarbose having IC 50 values 1.927 ± 0.17 μM. All compounds showed good α-amylase inhibition. Compound 14 was found to be the most potent analog among the series. Structure-activity relationship has been established for all compounds mainly based on bringing about the difference of substituents on phenyl ring. To understand the binding interaction of the most active analogs molecular docking study was performed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Despite of a diverse range of biological activities associated with chalcones and bis-chalcones, they are still neglected by the medicinal chemist for their possible α-amylase inhibitory activity. So, the current study is based on the evaluation of this class for the identification of new leads as α-amylase inhibitors. For that purpose, a library of substituted chalcones 1-13 and bis-chalcones 14-18 were synthesized and characterized by spectroscopic techniques EI-MS and 1 H NMR. CHN analysis was carried out and found in agreement with the calculated values. All compounds were evaluated for in vitro α-amylase inhibitory activity and demonstrated good activities in the range of IC 50  = 1.25 ± 1.05-2.40 ± 0.09 µM as compared to the standard acarbose (IC 50  = 1.04 ± 0.3 µM). Limited structure-activity relationship (SAR) was established by considering the effect of different groups attached to aryl rings on varying inhibitory activity. SMe group in chalcones and OMe group in bis-chalcones were found more influential on the activity than other groups. However, in order to predict the involvement of different groups in the binding interactions with the active site of α-amylase enzyme, in silico studies were also conducted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The α-amylase acts as attractive target to treat type-2 diabetes mellitus. Therefore in discovering a small molecule as α-amylase inhibitor, we have synthesized benzofuran carbohydrazide analogs (1-25), characterized through different spectroscopic techniques such as 1 HNMR and EI-MS. All screened analog shows good α-amylase inhibitory potentials with IC 50 value ranging between 1.078±0.19 and 2.926±0.05µM when compared with acarbose having IC 50 =0.62±0.22µM. Only nine analogs among the series such as analogs 3, 5, 7, 8, 10, 12, 21, 23 and 24 exhibit good inhibitory potential with IC 50 values 1.644±0.128, 1.078±0.19, 1.245±0.25, 1.843±0.19, 1.350±0.24, 1.629±0.015, 1.353±0.232, 1.359±0.119 and 1.488±0.07µM when compare with standard drug acarbose. All other analogs showed good to moderate α-amylase inhibitory potentials. The SAR study was conducted on the basis of substituent difference at the phenyl ring. The binding interaction between analogs and active site of enzyme was confirmed by docking studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

α-Amylase is a target for type-2 diabetes mellitus treatment. However, small molecule inhibitors of α-amylase are currently scarce. In the course of developing small molecule α-amylase inhibitors, we designed and synthesized thiadiazole quinoline analogs (1-30), characterized by different spectroscopic techniques such as 1 HNMR and EI-MS and screened for α-amylase inhibitory potential. Thirteen analogs 1, 2, 3, 4, 5, 6, 22, 23, 25, 26, 27, 28 and 30 showed outstanding α-amylase inhibitory potential with IC 50 values ranges between 0.002±0.60 and 42.31±0.17μM which is many folds better than standard acarbose having IC 50 value 53.02±0.12μM. Eleven analogs 7, 9, 10, 11, 12, 14, 15, 17, 18, 19 and 24 showed good to moderate inhibitory potential while seven analogs 8, 13, 16, 20, 21 and 29 were found inactive. Our study identifies novel series of potent α-amylase inhibitors for further investigation. Structure activity relationship has been established., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and 1 H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC 50 =0.38±0.82µM) and 23 (IC 50 =1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC 50 =1.77-2.98µM when compared with the standard acarbose (IC 50 =1.66±0.1µM). A plausible structure-activity relationship has also been presented. In addition, in silico studies was carried out in order to rationalize the binding interaction of compounds with the active site of enzyme., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A series of twenty indole hydrazone analogs (1-21) were synthesized, characterized by different spectroscopic techniques such as 1 H NMR and EI-MS, and screened for α-amylase inhibitory activity. All analogs showed a variable degree of α-amylase inhibition with IC 50 values ranging between 1.66 and 2.65μM. Nine compounds that are 1 (2.23±0.01μM), 8 (2.44±0.12μM), 10 (1.92±0.12μM), 12 (2.49±0.17μM), 13 (1.66±0.09μM), 17 (2.25±0.1μM), 18 (1.87±0.25μM), 20 (1.83±0.63μM), and 19 (1.97±0.02μM) showed potent α-amylase inhibition when compared with the standard acarbose (1.05±0.29μM). Other analogs showed good to moderate α-amylase inhibition. The structure activity relationship is mainly focusing on difference of substituents on phenyl part. Molecular docking studies were carried out to understand the binding interaction of the most active compounds., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Twenty five derivatives of indole carbohydrazide (1-25) had been synthesized. These compounds were characterized using 1 H NMR and EI-MS, and further evaluated for their α-amylase inhibitory potential. The analogs (1-25) showed varying degree of α-amylase inhibitory potential. ranging between 9.28 and 599.0µM when compared with standard acarbose having IC 50 value 8.78±0.16µM. Six analogs, 25 (IC 50 =9.28±0.153µM), 22 (IC 50 =9.79±0.43µM), 4 (IC 50 =11.08±0.357µM), 1 (IC 50 =12.65±0.169µM), 8 (IC 50 =21.37±0.07µM) and 14 (IC 50 =43.21±0.14µM) showed potent α-amylase inhibition as compared to the standard acarbose (IC 50 =8.78±0.16µM). All other analogs displayed good to moderate inhibitory potential. Structure-activity relationship was established through the interaction of the active compounds with enzyme active site with the help of docking studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The synthesis of novel indolopyrazoline derivatives (P1-P4 and Q1-Q4) has been characterized and evaluated as potential anti-Alzheimer agents through in vitro Acetylcholinesterase (AChE) inhibition and radical scavenging activity (antioxidant) studies. Specifically, Q3 shows AChE inhibition (IC50: 0.68±0.13μM) with strong DPPH and ABTS radical scavenging activity (IC50: 13.77±0.25μM and IC50: 12.59±0.21μM), respectively. While P3 exhibited as the second most potent compound with AChE inhibition (IC50: 0.74±0.09μM) and with DPPH and ABTS radical scavenging activity (IC50: 13.52±0.62μM and IC50: 13.13±0.85μM), respectively. Finally, molecular docking studies provided prospective evidence to identify key interactions between the active inhibitors and the AChE that furthermore led us to the identification of plausible binding mode of novel indolopyrazoline derivatives. Additionally, in-silico ADME prediction using QikProp shows that these derivatives fulfilled all the properties of CNS acting drugs. This study confirms the first time reporting of indolopyrazoline derivatives as potential anti-Alzheimer agents., (Copyright © 2016 Elsevier Inc. All rights reserved.)