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In this study, we have investigated a series of indole-based compounds for their inhibitory study against pancreatic α-amylase and intestinal α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes appear to have an essential role as antidiabetic drugs. All analogous exhibited good to moderate α-amylase (IC50 = 3.80 to 47.50 μM), and α-glucosidase inhibitory interactions (IC50 = 3.10–52.20 μM) in comparison with standard acarbose (IC50 = 12.28 μM and 11.29 μM). The analogues 4, 11, 12, 15, 14 and 17 had good activity potential both for enzymes inhibitory interactions. Structure activity relationships were deliberated to propose the influence of substituents on the inhibitory potential of analogues. Docking studies revealed the interaction of more potential analogues and enzyme active site. Further, we studied their kinetic study of most active compounds showed that compounds 15, 14, 12, 17 and 11 are competitive for α-amylase and non- competitive for α-glucosidase.

A series of seventeen analogs (1─17) were synthesized and characterized through different spectroscopic techniques such as 1H, 13CNMR, HR-EI-MS and were evaluated for in vitro thymidine phosphorylase inhibition. All compounds showed excellent to good thymidine phosphorylase activity having IC50 value ranging between 4.10 ± 0.20 and 54.60 ± 1.40 µM when compared with standard drug 7-deazaxanthine (IC50 = 38.68 ± 1.12 µM). Among the series, compounds 1 (IC50 = 8.30 ± 0.30 µM), 6 (IC50 = 6.30 ± 0.10 µM), 11 (IC50 = 8.40 ± 0.30 µM) and 16 (IC50 = 4.10 ± 0.20 µM) were found more potent. Potent compounds were further subjected to molecular docking study to identify their interactions with the active site of amino acid. Structure activity relationship was done for all analogs mostly based on substitution pattern on phenyl and isatin rings.

Aryl hydrazones bearing thiazolyl coumarin hybrids 1–32 were prepared by following 'one-pot' two-steps reaction scheme. Various arylaldehydes were reacted to thiosemicarbazide under acidic condition to form aryl thiosemicarbazone intermediates which in turn treated with 3-bromoacetyl coumarin under basic condition to afford thiazolyl coumarin hybrids 1–32. All hybrids were recognized by EI- and HREI-MS and 1H- and 13C-NMR spectroscopic techniques. Compounds 1–32 were screened for in vitro inhibitory activity against urease enzyme and displayed good to moderate inhibitory potential in the ranges of IC50 = 16.29 ± 1.1–256.30 ± 1.4 µM. Worth stating that compound 21 (IC50 = 16.29 ± 1.1 µM) was identified as more potent urease inhibitor than the standard acetohydroxamic acid (IC50 = 27.0 ± 0.5 µM). Derivatives 19 (IC50 = 77.67 ± 1.5 µM) and 30 (IC50 = 71.21 ± 1.6 µM) were found to be moderately active. Structure–activity relationship revealed that -F, -Cl, -OH, and -OMe groups and their respective positions on aryl ring are playing important role in urease enzyme inhibition. Molecular docking studies identified important interaction between the ligand (active hybrids) and urease active site.

N-Aryl-3,4-dihydroisoquinoline carbothioamide analogues 1-22 were synthesized by a simple one-step reaction protocol and subjected to in vitro urease inhibition studies for the first time. All compounds 1-22 were found active and showed significant to moderate urease inhibitory potential. Specifically, analogues 1, 2, 4, and 7 were identified to be more potent (IC50 = 11.2 ± 0.81-20.4 ± 0.22 μM) than the standard thiourea (IC50 = 21.7 ± 0.34 μM). The structure-activity relationship showed that compounds bearing electron-donating groups showed superior activity. Molecular docking study on the most active derivatives revealed a good protein-ligand interaction profile against the corresponding target with key interactions, including hydrogen bonding, hydrophobic, and π-anion interactions.

New benzimidazole derivatives were synthesized by reacting substituted phenacyl bromides with 1H-benzimidazole-2-thiols. The synthesized compounds were characterized through 1H and 13C NMR and high-resolution mass spectra. Their evaluation for α-amylase activity revealed inhibitory potential with IC50 values ranging from 1.20±0.05 to 19.10±0.30 μM against IC50 = 1.70±0.10 μM for the standard drug acarbose. Among the examined series, 2-[(1H-benzimidazole-2-yl)sulfanyl]-1-(3–nitrophenyl)ethan-1-one (IC50 = 1.20±0.05 µM) was the most potent. Other nitro-substituted analogs showed good potency with IC50 values of 2.10±0.10, 2.20±0.10 and 2.10±0.10 µM. Limited structure–activity relationship was established for all derivatives based on the nature, position, and number of substituents on the aryl ring. Binding sites of the most active compounds were determined by the molecular docking study.

In search of potent urease inhibitor indole analogues (1–22) were synthesized and evaluated for their urease inhibitory potential. All analogues (1–22) showed a variable degree of inhibitory interaction potential having IC50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90 µM when compared with standard thiourea having IC50 value 21.86 ± 0.90 µM. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05 µM respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed. Communicated by Ramaswamy H. Sarma

A variety of dihydroquinazolin-4(1H)-one derivatives (1–37) were synthesized via “one-pot” three-component reaction scheme by treating aniline and different aromatic aldehydes with isatoic anhydride in the presence of acetic acid. Chemical structures of compounds were deduced by different spectroscopic techniques including EI-MS, HREI-MS, 1H-, and 13C-NMR. Compounds were subjected to α-amylase and α-glucosidase inhibitory activities. A number of derivatives exhibited significant to moderate inhibition potential against α-amylase (IC50 = 23.33 ± 0.02—88.65 ± 0.23 μM) and α-glucosidase (IC50 = 25.01 ± 0.12—89.99 ± 0.09 μM) enzymes, respectively. Results were compared with the standard acarbose (IC50 = 17.08 ± 0.07 μM for α-amylase and IC50 = 17.67 ± 0.09 μM for α-glucosidase). Structure–activity relationship (SAR) was rationalized by analyzing the substituents effects on inhibitory potential. Kinetic studies were implemented to find the mode of inhibition by compounds which revealed competitive inhibition for α-amylase and non-competitive inhibition for α-glucosidase. However, in silico study identified several important binding interactions of ligands (synthetic analogues) with the active site of both enzymes.

Functionalized quinazolinone derivatives 1–30 were synthesized by two-step reaction. First, anthranilic acid was treated with substituted phenyl isothiocyanate to synthesize 3-aryl-2-thioxo-2,3-dihydroquinazolinone derivatives 1–8 which in turn reacted with different bromoacetophenone derivatives to obtain fully functionalized quinazolinone derivatives 9–30. Both reactions were catalyzed by triethylamine. All the products were characterized by EI-, HREI-MS, 1H-, and 13CNMR spectroscopic techniques. All compounds were subjected to their in vitro α-glucosidase inhibitory activity. Results showed that except compound 1–3, 5, 7, and 22, all compounds were found potent and showed many folds increased α-glucosidase enzyme inhibition as compared to standard acarbose (IC50 = 750.0 ± 10.0 µM). Compound 13 (IC50 = 85.0 ± 0.5 µM) was recognized as the most potent analog of the whole series, with ninefold enhanced inhibitory potential than the standard acarbose. Compounds 1–9, 11, 12, 22, and 26 were structurally known compounds, while remaining all are new. Kinetic study on compound 13 showed that the compound is following a competitive-type inhibition mechanism. Furthermore, in silico studies have also been performed to better rationalize the interactions between synthetic compound and active site of the enzyme.

Indole-3-acetamides (1–24) were synthesized via coupling of indole-3-acetic acid with various substituted anilines in the presence of coupling reagent 1,1-carbonyldiimidazole. The structures of synthetic molecules were elucidated through different spectroscopic techniques including electron ionization-mass spectroscopy (EI-MS), 1H-, 13C NMR, and high-resolution EI-MS (HREI-MS). These compounds were screened for their antihyperglycemic and antioxidant potentials. All compounds displayed good to moderate inhibition against α-amylase enzyme with IC50 values ranging between 1.09 ± 0.11 and 2.84 ± 0.1 μM compared to the standard acarbose (IC50 = 0.92 ± 0.4 μM). Compound 15 (IC50 = 1.09 ± 0.11 μM) was the most active compound of the series and exhibited good inhibition against α-amylase; in addition, this compound also exhibited good antioxidant potential with IC50 values of 0.35 ± 0.1 and 0.81 ± 0.25 μM in 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, respectively. The binding interactions of synthetic molecules with the enzyme’s active site were confirmed via in silico studies. The current study had identified a number of lead molecules as potential antihyperglycemic and antioxidant agents.

α-Glucosidase and α-amylase are enzymes which are associated with diabetic II. These enzymes break macromolecules of sugar into monosugar molecules which is soluble in body, hence increase the sugar level in blood. There is need to develop economical and save inhibitors to prevent them from breaking sugar macromolecules to soluble molecules which will control the level of sugar in blood. Therefore, we synthesized indole-based derivatives (1–18) and evaluated as dual inhibitor for α-glucosidase and α-amylase. These chemical scaffolds were built with variation in aryl ring which were found active with good to moderate activity for α-glucosidase having IC50 value ranging from 13.99 ± 0.10 to 59.09 ± 0.30 μM when compared with standard acarbose with IC50 of 11.29 ± 0.10 μM; for α-amylase IC50 value ranging from 13.14 ± 0.10 to 58.99 ± 0.30 μM when compared with the standard acarbose with IC50 of 11.12 ± 0.10 μM. Structure activity relationship (SAR) has been established for all compounds. Enzymatic kinetic study and molecular docking study have been carried out to investigate the binding interactions α-glucosidase and α-amylase enzyme.

The current study describes synthesis of diindolylmethane (DIM) derivatives based-thiadiazole as a new class of urease inhibitors. Diindolylmethane is natural product alkaloid reported to use in medicinal chemistry extensively. Diindolylmethane-based-thiadiazole analogs (1–18) were synthesized and characterized by various spectroscopic techniques 1HNMR, 13C-NMR, EI-MS and evaluated for urease (jack bean urease) inhibitory potential. All compounds showed excellent to moderate inhibitory potential having IC50 value within the range of 0.50 ± 0.01 to 33.20 ± 1.20 µM compared with the standard thiourea (21.60 ± 0.70 µM). Compound 8 (IC50 = 0.50 ± 0.01 µM) was the most potent inhibitor amongst all derivatives. Structure-activity relationships have been established for all compounds. The key binding interactions of most active compounds with enzyme were confirmed through molecular docking studies.

α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC50 values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC50 = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC50 = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data. Keywords: Synthesis, Aryl-oxadiazole Schiff bases, α-glucosidase, Molecular docking, Structure-activity relationship (SAR)

Novel ibuprofen derivatives 1–19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2–19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, 1H-, and 13C-NMR spectroscopic techniques. The synthetic molecules 1–19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC50 = 2.96–178 μM as compared to the standard thiourea (IC50 = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2–4, 6, 7, 9, 11–15, 17, and 18 demonstrated remarkable inhibitory activity with IC50 values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC50 value of 37.3 ± 0.41 μM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure–activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme.

New benzimidazole analogues (1–18) were synthesized and characterized through different spectroscopic techniques such as 1H NMR, 13C NMR and HREI-MS. All analogues were screened for β-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC50 values ranging between 1.10 ± 0.10 to 39.60 ± 0.70 μM when compared with standard D-saccharic acid-1,4- lactone having IC50 value 48.30 μM. Analogues 17, 11, 9, 6, 1 and 13 having IC50 values 1.10 ± 0.10, 1.70 ± 0.10, 2.30 ± 0.10, 5.30 ± 0.20, 6.20 ± 0.20 and 8.10 ± 0.20 μM respectively, showed excellent β-glucuronidase inhibitory potential many folds better than the standard. All other analogues also showed good inhibitory potential better as compared to standard. Structure activity relationships (SAR) has been established for all compounds. The results from molecular docking studies supports the established SAR and developed a strong correlation with the results from in to vitro assay. The molecular docking results clearly highlighted how substituents like nitro and chloro affect the binding position of the active compounds in the active site. The docking results were also used to properly establish the effect of bulky substituents of least active compounds on reduced β-glucuronidase inhibitory activity. Compounds 1–18 were found non-toxic.

In the continuation of our work to synthesize enzyme inhibitors, we synthesized 3,4,5-trihydroxybenzohydrazones (1–19) from 3,4,5-trihydroxybenzohydrazide, which were obtained from methyl 3,4,5-trihydroxybenzoate by refluxing with hydrazine hydrate. All the synthesized compounds were characterized by different spectroscopic methods. The synthesized compounds were evaluated for urease inhibition and showed excellent results, close to the standards thiourea. The kinetic studies on the five most active compounds 6, 10, 14, 16 and 18 were carried out to determine their mode of inhibition and dissociation constant Ki. The compounds 6 and 16 were found to be competitive inhibitors with Ki values 19.1 and 10.53 μM, respectively, while the compounds 10, 14 and 18 were found to be mixed-type of inhibitors with Ki values in the range of 18.4–21.7 μM. Keywords: 3,4,5-Trihydroxybenzohydrazones, Urease inhibition, Kinetic study

Herein, we report the synthesis and inhibitory potential of indazole (Methyl 1H-indazole-4-carboxylate) derivatives (1–13) against α-amylase and α-glucosidase enzymes. The described derivatives demonstrated good inhibitory potential with IC50 values, ranging between 15.04 ± 0.05 to 76.70 ± 0.06 µM ± SEM for α-amylase and 16.99 ± 0.19 to 77.97 ± 0.19 µM ± SEM for α-glucosidase, respectively. In particular, compounds (8–10 and 12) displayed significant inhibitory activities against both the screened enzymes, with their inhibitory potential comparable to the standard acarbose (12.98 ± 0.03 and 12.79 ± 0.17 µM ± SEM, respectively). Additionally, the influence of different substituents on enzyme inhibition activities was assessed to study the structure activity relationships. Molecular docking simulations were performed to rationalize the binding of derivatives/compounds with enzymes. All the synthesized derivatives (1–13) were characterized with the aid of spectroscopic instruments such as 1H-NMR, 13C-NMR, HR-MS, elemental analysis and FTIR. Communicated by Ramaswamy H. Sarma

We have synthesized nineteen (1–19) bisindolylmethane sulfonamide analogs, characterized by different spectroscopic techniques such as 1HNMR and EI-MS and tested for α-amylase inhibitory potential. All compounds showed excellent to moderate degree of α-amylase inhibitory potential with IC50 values ranging between 1.192 ± 0.51 to 3.057 ± 0.18 μM as equated with standard acarbose (IC50 values 0.83 ± 0.36 μM). Among the series, six analogs such as 1, 4, 5, 6, 10, and 14 showed potent α-amylase inhibition with IC50 values 1.747 ± 0.2, 1.208 ± 0.15, 1.192 ± 0.51, 1.858 ± 0.08, 1.358 ± 0.27 and 1.527 ± 0.17 μM, respectively, as equated with standard acarbose. The structure-activity relationship based upon different substituents on phenyl part. Molecular docking studies performed to recognize the binding interaction of the most active compounds.

In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1–25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC50 = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC50values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC50 = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like 1H NMR, 13C NMR and ESIMS were used for characterization.

A new series of oxadiazole with thiadiazole moiety (6–27) were synthesized, characterized by different spectroscopic techniques and evaluated for β-glucuronidase inhibitory potential. Sixteen analogs such as 6, 7, 8, 9, 10, 12, 13, 14, 17, 18, 20, 23, 24, 25, 26 and 27 showed IC50 values in the range of 0.96 ± 0.01 to 46.46 ± 1.10 μM, and hence were found to have excellent inhibitory potential in comparison to standard d -saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Two analogs such as 16 and 19 showed moderate inhibitory potential while analogs 11, 15, 21 and 22 were found inactive. Our study identifies new series of potent β-glucuronidase inhibitors for further investigation. Structure activity relationships were established for all compounds which showed that the activity is varied due to different substituents on benzene ring. The interaction of the compounds with enzyme active site were confirmed with the help of docking studies, which reveals that the electron withdrawing group and hydroxy group make the molecules more favorable for enzyme inhibition.

New series of quinoline-based thiadiazole analogs (1–20) were synthesized, characterized by EI-MS, 1H NMR and 13C NMR. All synthesized compounds were subjected to their antileishmanial potential. Sixteen analogs 1–10, 12, 13, 16, 17, 18 and 19 with IC50 values in the range of 0.04 ± 0.01 to 5.60 ± 0.21 µM showed tremendously potent inhibition as compared to the standard pentamidine with IC50 value 7.02 ± 0.09 µM. Analogs 11, 14, 15 and 20 with IC50 8.20 ± 0.35, 9.20 ± 0.40, 7.20 ± 0.20 and 9.60 ± 0.40 µM respectively showed good inhibition when compared with the standard. Structure-activity relationships have been also established for all compounds. Molecular docking studies were performed to determine the binding interaction of the compounds with the active site target.

Background Indole based thiadiazole derivatives (1–22) have synthesized, characterized by NMR and HREI-MS and evaluated for β-Glucuronidase inhibition. All compounds showed outstanding β-glucuronidase activity with IC50 values ranging between 0.5 ± 0.08 to 38.9 ± 0.8 µM when compared with standard d-saccharic acid 1,4 lactone (IC50 value of 48.1 ± 1.2 µM). The compound 6, a 2,3-dihydroxy analog was found the most potent among the series with IC50 value 0.5 ± 0.08 µM. Structure activity relationship has been established for all compounds. To confirm the binding interactions of these newly synthesized compounds, molecular docking study have been carried out which reveal that these compounds established stronger hydrogen bonding networks with active site residues. Electronic supplementary material The online version of this article (10.1186/s13065-019-0522-x) contains supplementary material, which is available to authorized users.

In continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1–14) were synthesized, characterized by HREI-MS, 1H and 13CNMR and evaluated for urease inhibition. Compounds 1–14 exhibited a varying degree of urease inhibitory activity with IC50 values between 1.2 ± 0.01 to 23.50 ± 0.70 µM when compared with standard drug thiourea having IC50 value 21.40 ± 0.21 µM. Compound 1, 3, 5 and 8 showed significant inhibitory effects with IC50 values 1.2 ± 0.01, 2.20 ± 0.01, 1.40 ± 0.01 and 2.90 ± 0.01 µM respectively, better than the rest of the series. A structure activity relationship (SAR) of this series has been established based on electronic effects and position of different substituents present on phenyl ring. Molecular docking studies were performed to understand the binding interaction of the compounds.

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 (IC50 = 23.08 ± 0.03 µM), (IC50 = 26.08 ± 0.43 µM), 5 (IC50 = 24.57 ± 0.07 µM), (IC50 = 27.57 ± 0.07 µM), 6 (IC50 = 24.94 ± 0.12 µM), (IC50 = 27.13 ± 0.08 µM), 16 (IC50 = 27.57 ± 0.07 µM), (IC50 = 29.13 ± 0.18 µM), and 28 (IC50 = 26.94 ± 0.12 µM) (IC50 = 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.

(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 IC50 values ranging (IC50 = 13.02 ± 0.04–46.90 ± 0.05 µM) and (IC50 = 13.09 ± 0.08–46.44 ± 0.24 µM) in comparison to standard acarbose (IC50 = 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

In search of better α-glucosidase inhibitors, a series of bis-indolylmethane sulfonohydrazides derivatives (1-14) were synthesized and evaluated for their α-glucosidase inhibitory potential. All derivatives exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 0.10 ± 0.05 to 5.1 ± 0.05 μM when compared with standard drug acarbose having IC50 value 856.28 ± 3.15 μM. Among the series, analog 7 (0.10 ± 0.05 μM) with tri-chloro substitution on phenyl ring was identified as the most potent inhibitor of α-glucosidase (∼ 8500 times). The structure activity relationship has been also established. Molecular docking studies were also performed to help understand the binding interaction of the most active analogs with receptors. From the docking studies, it was observed that all the active bis-indolylmethane sulfonohydrazides derivatives showed considerable binding interactions within the active site (acarbose inhibition site) of α-glucosidase. We also evaluated toxicity of all derivatives and found none of them are toxic.

Thymidine phosphorylase is an enzyme involved in pyrimidine salvage pathway that is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is enormously up regulated in a variety of solid tumors. Furthermore, surpassing of TP level protects tumor cells from apoptosis and helps cell survival. Thus TP is identified as a prime target for developing novel anticancer therapies. A new class of exceptionally potent isatin based oxadiazole (1–30) has been synthesized and evaluated for thymidine phosphorylase inhibitory potential. All analogs showed potent thymidine phosphorylase inhibition when compared with standard 7-Deazaxanthine, 7DX (IC50 = 38.68 ± 1.12 µM). Molecular docking study was performed in order to determine the binding interaction of these newly synthesized compounds, which revealed that these synthesized compounds established stronger hydrogen bonding network with active site of residues as compare to the standard compound 7DX.

Thirty-three 4-amino-1,2,4-triazole derivatives 1–33 were synthesized by reacting 4-amino-1,2,4-triazole with a variety of benzaldehydes. The synthetic molecules were characterized via 1H NMR and EI-MS spectroscopic techniques and evaluated for their anti-hyperglycemic potential. Compounds 1–33 exhibited good to moderate in vitro α-amylase and α-glucosidase inhibitory activities in the range of IC50 values 2.01 ± 0.03–6.44 ± 0.16 and 2.09 ± 0.08–6.54 ± 0.10 µM as compared to the standard acarbose (IC50 = 1.92 ± 0.17 µM) and (IC50 = 1.99 ± 0.07 µM), respectively. The limited structure-activity relationship suggested that different substitutions on aryl part of the synthetic compounds are responsible for variable activity. Kinetic study predicted that compounds 1–33 followed mixed and non-competitive type of inhibitions against α-amylase and α-glucosidase enzymes, respectively. In silico studies revealed that both triazole and aryl ring along with different substitutions were playing an important role in the binding interactions of inhibitors within the enzyme pocket. The synthetic molecules were found to have dual inhibitory potential against both enzymes thus they may serve as lead candidates for the drug development and research in the future studies.

We have synthesized oxadiazole derivatives (1–16), characterized by 1H NMR, 13C NMR and HREI-MS and screened for thymidine phosphorylase inhibitory potential. All derivatives display varied degree of thymidine phosphorylase inhibition in the range of 1.10 ± 0.05 to 49.60 ± 1.30 μM when compared with the standard inhibitor 7-Deazaxanthine having an IC50 value 38.68 ± 1.12 μM. Structure activity relationships (SAR) has been established for all compounds to explore the role of substitution and nature of functional group attached to the phenyl ring which applies imperious effect on thymidine phosphorylase activity. Molecular docking study was performed to understand the binding interaction of the most active derivatives with enzyme active site.

Inhibition of Thymidine phosphorylase (TP) is continuously studied for the design and development of new drugs for the treatment of neoplastic diseases. As a part of our effort to identify TP inhibitors, we performed a structure-based virtual screening (SBVS) of our compound collection. Based on the insights gained from structures of virtual screening hits, a scaffold was designed using 1,3,4-oxadiazole as the basic structural feature and SAR studies were carried out for the optimization of this scaffold. Twenty-five novel bis -indole linked 1,3,4-oxadiazoles ( 7 – 31 ) were designed, synthesized and tested in vitro against E. coli TP ( Ec TP). Compound 7 emerged as potent TP inhibitor with an IC 50 value of 3.50 ± 0.01 μM. Docking studies were carried out using GOLD software on thymidine phosphorylase from human ( h TP) and E. coli ( Ec TP). Various hydrogen bonding, hydrophobic interactions, and π-π stacking were observed between designed molecules and the active site amino acid residues of the studied enzymes.

This study is focused on the identification of thiazole-based inhibitors for the $$\alpha $$ -glucosidase enzyme. For that purpose, (E)-2-(2-(arylmethylene)hydrazinyl)-4-arylthiazole derivatives were synthesized in two steps and characterized by various spectroscopic techniques. All derivatives and intermediates were evaluated for their in vitro $$\alpha $$ -glucosidase inhibitory activity. Thiosemicarbazones 20 and 35, and cyclized thiazole derivatives 2, 5–11, 13, 15, 21–24, 27–31, and 36–37 showed significant inhibitory potential in the range of $$\hbox {IC}_{50}=6.2\pm 0.19$$ – $$43.6\pm 0.23~\upmu \hbox {M}$$ as compared to standard acarbose ( $$\hbox {IC}_{50}=37.7\pm 0.19~\upmu \hbox {M}$$ ). A molecular modeling study was carried out to understand the binding interactions of compounds with the active site of enzyme.

Inhibition of α-glucosidase is an effective strategy for controlling post-prandial hyperglycemia in diabetic patients. Beside these α-glucosidase inhibitors has been also used as anti-obesity and anti-viral drugs. Keeping in view the greater importance of α-glucosidase inhibitors here in this study we are presenting oxindole based oxadiazoles hybrid analogs (1-20) synthesis, characterized by different spectroscopic techniques including 1H NMR and EI-MS and their α-glucosidase inhibitory activity. All compounds were found potent inhibitors for the enzyme with IC50 values ranging between 1.25 ± 0.05 and 268.36 ± 4.22 µM when compared with the standard drug acarbose having IC50 value 895.09 ± 2.04 µM. Our study identifies novel series of potent α-glucosidase inhibitors and further investigation on this may led to the lead compounds. A structure activity relationship has been established for all compounds. The interactions of the active compounds and enzyme active site were established with the help of molecular docking studies.

Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies.

Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1–32 were synthesized and characterized by 1HNMR, 13CNNMR and HREI-MS. All compounds were evaluated in vitro for β-glucuronidase inhibitory potential. All analogs showed varying degree of β-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 μM when compared with the standard drug d -saccharic acid-1,4-lactone (IC50 value 48.30 ± 1.20 μM). Derivatives 1–32 showed the highest β-glucuronidase inhibitory potentials which is many folds better than the standard drug d -saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of β-glucuronidase enzyme. This study has culminated in the identification of a new class of potent β-glucuronidase inhibitors.

Benzohydrazide bearing thiourea/Schiff base analogs (1a-1k, 2a-2q) were synthesized and characterized through 1H, 13CNMR, HR-EIMS, FT-IR analysis. Urease inhibitory potential of all synthesized analogs were evaluated showing excellent inhibitory potential ranging between 0.6 ± 0.01 to 14.30 ± 0.02 and 0.80 ± 0.01 to 29.60 ± 1.00 μM respectively when compared with the standard drug thiourea (IC50 = 21.40 ± 0.21 μM). Analog 1b (IC50 = 0.6 ± 0.01 µM) was the most potent in benzohydrazide bearing thiourea series, while analog 2i (IC50 = 0.80 ± 0.01 μM) was the most potent in benzohydrazide bearing Schiff bases series. Our current study reveals new series of urease inhibitors for further analysis. Structure activity relationship was established to explore the effect of different substituent's attached to phenyl ring. Binding interactions of most potent analogs were established with help of docking studies.

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 ± 0.05 µM when compared with acarbose having IC 50 = 0.62 ± 0.22 µM. 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 ± 0.07 µM 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.

3,4-Dimethoxybenzohydrazide derivatives ( 1–25 ) have been synthesized and evaluated for their urease inhibitory potential. Among the series, compounds 2 , 3 , 4 and 5 with IC 50 values 12.61 ± 0.07, 18.24 ± 0.14, 19.22 ± 0.21, and 8.40 ± 0.05 µM, respectively, showed excellent urease inhibitory potentials when compared with standard thiourea (IC 50 value 21.40 ± 0.21 µM). Compounds 1 , 6 , 8 , 18 , 19 and 20 also showed good to moderate inhibition, while the remaining compounds were found to be completely inactive. The structures of compounds 6 and 25 were confirmed through X-ray crystallography while the structures of remaining compounds were confirmed through ESI-MS and 1 H NMR. Molecular docking studies were performed understand the binding interactions with enzyme active site. The synthesized compounds were evaluated for cytotoxicity and found to be nontoxic.

Indazole Schiff bases were synthesized 1–24 and structurally characterized by different spectroscopic techniques such as EI-MS, HREI-MS, 1H- and 13C-NMR. Stereochemistry of azomethine moiety in synthesized compounds was confirmed by 2D-NOESY. Among the twenty-four compounds, fourteen compounds 1–5, 7, 9–14, 17, and 20 are structurally new. Compounds 1–24 were screened for in vitro α-glucosidase enzyme inhibitory activity. All compounds were In vitro α-glucosidase inhibitory assay results identified a number of molecules including 1, 2, 4, 7, 9, 10, 12, 13, 18, 19, 21, and 23 as potent α-glucosidase inhibitors with IC50 values 9.4 ± 0.1 to 303.7 ± 0.1 μM as compared to the standard acarbose (IC50 = 750 ± 10 µM). Compound 1 (IC50 = 9.43 ± 0.1 µM) was found to be the most potent molecule of this library. Kinetic studies on most active compound 1 suggested the competitive inhibition mechanism. In silico studies indicated the interaction details between analogs (ligands) and active site of α-glucosidase enzyme.

An enhanced acetylcholinesterase (AChE) activity is a hallmark in early stages of Alzheimer's ailment that results in decreased acetylcholine (ACh) levels, which in turn leads to cholinergic dysfunction and neurodegeneration. Consequently, inhibition of both AChE and butyrylcholinesterase (BChE) is important to prolong ACh activity in synapses for the enhanced cholinergic neurotransmission. In this study, a series of new fluoroquinolone derivatives (7a-m) have synthesized and evaluated for AChE and BChE inhibitory activities. The screening results suggested that 7 g bearing ortho fluorophenyl was the most active inhibitor against both AChE and BChE, exhibiting IC50 values of 0.70 ± 0.10 µM and 2.20 ± 0.10 µM, respectively. The structure–activity relationship (SAR) revealed that compounds containing electronegative functions (F, Cl, OMe, N and O) at the ortho position of the phenyl group exhibited higher activities as compared to their meta- and/or para substituted counterparts. Molecular docking studies of synthesized compounds 7a, 7g, 7j and 7l docked into the active site of AChE and 7a-f docked into the active site of BChE revealed that these compounds exhibited conventional H-bonding along with π-π interaction with the active residues of AChE through their electronegative functions and phenyl ring, respectively. All the synthesized compounds are characterized by spectroscopic methods including FT-IR, 1H- and 13C NMR as well as elemental analysis. This is the first example of fluoroquinolone-based cholinesterase inhibitors.

In the search of potent α-amylase inhibitors, we have synthesized seventeen derivatives of 2-mercaptobenzimidazole bearing sulfonamide (1–17) and evaluated for their α-amylase inhibitory potential. All synthesized compounds display a variable degree of α-amylase activity having IC50 values ranging between 0.90 ± 0.05 to 11.20 ± 0.30 µM when compared with the standard drug acarbose having IC50 value 1.70 ± 0.10 µM. Compound 1, 2, 11, 12 and 14 having IC50 values 1.40 ± 0.10, 1.30 ± 0.05, 0.90 ± 0.05, 1.60 ± 0.05 and 1.60 ± 0.10 µM respectively were found many folds better than the standard drug acarbose. While others derivatives of the series showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C NMR spectroscopy. Structure activity relationship (SAR) has been established for all newly synthesized analogs. Binding interactions between ligands and active residues of the enzyme were confirmed through molecular docking study.

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 ± 0.17 μM which is many folds better than standard acarbose having IC 50 value 53.02 ± 0.12 μM. 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.

A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives ( 1 − 2 3 ) 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 ± 0.82 µM) and 23 (IC 50 = 1.66 ± 0.14 µM), showed excellent activity whereas the remaining compounds, except 10 and 17 , showed good to moderate inhibition in the range of IC 50 = 1.77–2.98 µM when compared with the standard acarbose (IC 50 = 1.66 ± 0.1 µM). 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.

A series of twenty indole hydrazone analogs (1-21) were synthesized, characterized by different spectroscopic techniques such as 1H NMR and EI-MS, and screened for α-amylase inhibitory activity. All analogs showed a variable degree of α-amylase inhibition with IC50 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.

Novel sulfonamides having oxadiazole ring were synthesized by multistep reaction and evaluated to check in vitro β -glucuronidase inhibitory activity. Luckily, except compound 13 , all compounds were found to demonstrate good inhibitory activity in the range of IC 50 = 2.40 ± 0.01–58.06 ± 1.60 μM when compared to the standard d -saccharic acid 1,4-lactone (IC 50 = 48.4 ± 1.25 μM). Structure activity relationship was also presented. However, in order to ensure the SAR as well as the molecular interactions of compounds with the active site of enzyme, molecular docking studies on most active compounds 19 , 16 , 4 and 6 was carried out. All derivatives were fully characterized by 1 H NMR, 13 C NMR and EI-MS spectroscopic techniques. CHN analysis was also presented.

A new class of triazinoindole-bearing thiosemicarbazides (1&ndash, 25) was synthesized and evaluated for &alpha, glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, with IC50 values ranging from 1.30 &plusmn, 0.01 to 35.80 &plusmn, 0.80 &micro, M when compared to standard acarbose (an IC50 value of 38.60 &plusmn, 0.20 &micro, M). Among the series, analogs 1 and 23 were found to be the most potent, with IC50 values of 1.30 &plusmn, 0.05 and 1.30 &plusmn, 0.01 &micro, M, respectively. The structure&ndash, activity relationship (SAR) was mainly based upon bringing about different substituents on the phenyl rings. To confirm the binding interactions, a molecular docking study was performed.

New class of triazinoindole bearing thiosemicarbazide (1-25) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogues exhibited excellent inhibitory potential having IC50 values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared with the standard acarbose having IC50 value 38.60 ± 0.20 µM. Among series the analogues 1 and 23 was found the most potent having IC50 values 1.30 ± 0.05 and 1.30 ± 0.01 µM respectively. Structure activity relationship (SAR) was mainly based upon by bring about difference of substituents on phenyl rings. To confirm the binding interactions, molecular docking study was performed. Synthesized analogues were characterized through HREI-MS, 1H and 13C-NMR analysis.

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 IC50 = 2.21 ± 0.06–9.97 ± 0.08 µM, as compared to the standard drug acarbose (IC50 = 2.01 ± 0.1 µM) and α-glucosidase inhibition in the range of IC50 = 2.31 ± 0.09–9.9 ± 0.1 µM as compared to standard acarbose (IC50 = 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 1H, 13C NMR, EI-MS, and HREI-MS were used to characterize all the synthetic compounds.

Voglibose and acarbose are distinguished α-glucosidase inhibitors used for controlling of diabetes mellitus. Unfortunately, these distinguished and clinically used inhibitors have also numerous side effects. Subsequently, there is still needed to develop safer therapy. Despite of a broad spectrum of biological importance of benzimidazole, it is occasionally evaluated for α-glucosidase activity. Current study deals with the synthesis and biological screening of benzimidazole bearing bis-Schiff bases (1–19) for their α-glucosidase inhibitory activity. All analogues exhibited excellent to good inhibitory potential (IC50 = 2.20 ± 0.1to 88.60 ± 1.70 µM) when compared with standard drug acarbose (IC50 = 38.45 ± 0.80 µM). A structure activity relationship has been established on the basis of electronic effects and position of different substituents present on phenyl ring. In order to rationalize the binding interactions of most active analogues with the active site of α-glucosidase enzyme, molecular docking study was conducted.

New triazinoindole bearing thiazole/oxazole analogues (1–21) were synthesized and characterized through spectroscopic techniques such as HREI-MS, 1H and 13C NMR. The configuration of compound 2i and 2k was confirmed through NOESY. All analogues were evaluated against α-amylase inhibitory potential. Among the synthesized analogues, compound 1h, 1i, 1j, 2a and 2f having IC50 values 1.80 ± 0.20, 1.90 ± 0.30, 1.2 ± 0.30, 1.2 ± 0.01 and 1.30 ± 0.20 μM respectively, showed excellent α-amylase inhibitory potential when compared with acarbose as standard (IC50 = 0.91 ± 0.20 µM). All other analogues showed good to moderate inhibitory potential. Structural activity relationship (SAR) has been established and binding interactions were confirmed through docking studies.