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Graphical abstract Highlights • Syntheses of benzophenone sulfonamide analogs have been carried out. • Structures of all synthetic compounds were elucidated by spectroscopic techniques. • Urease inhibitory activity of synthetic compounds has been carried out. • In silico studies of active analogs have been performed. • Structure-activity relationship has been evaluated. Abstract This study deals with the synthesis of benzophenone sulfonamides hybrids (1 – 31) and screening against urease enzyme in vitro. Studies showed that several synthetic compounds were found to have good urease enzyme inhibitory activity. Compounds 1 (N ′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-nitrobenzenesulfonohydrazide), 2 (N ′-((4′-hydroxyphenyl)(phenyl)methylene)-3′′-nitrobenzenesulfonohydrazide), 3 (N ′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-methoxybenzenesulfonohydrazide), 4 (3′′,5′′-dichloro-2′′-hydroxy- N ′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 6 (2′′,4′′-dichloro- N ′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 8 (5-(dimethylamino)- N ′-((4-hydroxyphenyl)(phenyl)methylene)naphthalene-1-sulfono hydrazide), 10 (2′′-chloro- N ′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 12 (N ′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide) have found to be potently active having an IC 50 value in the range of 3.90–17.99 µM. These compounds showed superior activity than standard acetohydroxamic acid (IC 50 = 29.20 ± 1.01 µM). Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease enzyme. Structures of all the synthetic compounds were elucidated by 1H NMR, 13C NMR, EI-MS and FAB-MS spectroscopic techniques. [ABSTRACT FROM AUTHOR]

• Indole acrylonitriles (3 – 23) were synthesized and characterized through different spectroscopic techniques. • The synthetic molecules were evaluated for their potential for α- glucosidase inhibition. • Acarbose (IC 50 = 2.91 ± 0.02 μM) was used as standard. • Molecular docking of synthetic compounds was performed to verify the binding interactions of ligand with the active site of enzyme. One of the most prevailing metabolic disorder diabetes mellitus has become the global health issue that has to be addressed and cured. Different marketed drugs have been made available for the treatment of diabetes but there is still a need of introducing new therapeutic agents that are economical and have lesser or no side effects. The current study deals with the synthesis of indole acrylonitriles (3 – 23) and the evaluation of these compounds for their potential for α- glucosidase inhibition. The structures of these synthetic molecules were deduced by using different spectroscopic techniques. Acarbose (IC 50 = 2.91 ± 0.02 μM) was used as standard in this study and the synthetic molecules (3 – 23) have shown promising α- glucosidase inhibitory activity. Compounds 4 , 8 , 10 , 11 , 14 , 18 , and 21 displayed superior inhibition of α -glucosidase enzyme in the range of (IC 50 = 0.53 ± 0.01–1.36 ± 0.04 μM) as compared to the standard acarbose. Compound 10 (IC 50 = 0.53 ± 0.01 μM) was the most effective inhibitor of this library and displayed many folds enhanced activity in contrast to the standard. Molecular docking of synthetic compounds was performed to verify the binding interactions of ligand with the active site of enzyme. This study had identified a number of potential α- glucosidase inhibitors that can be used for further research to identify a potent therapeutic agent against diabetes. [ABSTRACT FROM AUTHOR]

• Schiff bases of 4-amino-1,2,4-triazole were synthesized and evaluated for their in vitro anti hyperglycemic potential. • Kinetics confirmed that both enzymes are inhibited via different modes. • The binding interactions of molecules within the active site of enzyme was confirmed through molecular docking studies. 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 IC 50 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 (IC 50 = 1.92 ± 0.17 µM) and (IC 50 = 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. [ABSTRACT FROM AUTHOR]