Synthesis, Biological Evaluation, QSAR, Molecular Docking and ADMET Studies of N-aryl/N,N-dimethyl Substituted Sulphonamide Derivatives

(E-pub Ahead of Print)

Author(s): Samridhi Thakral, Vikramjeet Singh*.

Journal Name: Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry

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Background: Rapid evolution of drug resistance and side effects of currently used drugs urges to develop more efficacious and newer antimicrobial agents. Further for the management of Type II Diabetes, α-gulcosidase and α-amylase inhibitors play a very important role by inhibiting the postprandial hyperglycemia.

Objective: The objective of this study was to synthesize N-aryl/N,N-dimethyl sulphonamides, investigate their antihyperglycemic and antimicrobial potential, develop QSAR model for identifying molecular descriptors, predict their binding modes and in silico ADMET properties.

Method: Synthesized derivatives were subjected to in vitro studies for their antidiabetic activity against α-glucosidase and α-amylase enzymes and antimicrobial activity. Molecular docking studies were carried out to find out molecular binding interactions of the ligand molecules with their respective targets. QSAR studies were carried out to identify structural determinants responsible for antimicrobial activity.

Results: Antidiabetic study demonstrated the potent activity of two compounds 2 and 6 as α-glucosidase and α-amylase inhibitors as well as compound 1 and 2 exhibited potent antimicrobial activity against all the tested microbes. All the compounds were found to have more antifungal potential against Candida albicans. QSAR studies confirmed the role of molecular connectivity indices (valence first order and second order) in controlling the antimicrobial activity. Molecular docking studies supported the observed in vitro biological activities of the synthesized compounds.

Conclusion: The compounds with 2,3-dimethyl substitution was found to be antidiabetic agents and molecules having bromo and 2,3-dimethyl substituents on phenyl ring have established themselves as potent antimicrobial agents. The role of valence first and 2nd order molecular connectivity indices as molecular properties were identified for antimicrobial activity and various electrostatic, hydrogen bonding, hydrophobic interactions were found to be prominent in binding of molecules at target site.

Keywords: Sulphonamides, antidiabetic, antimicrobial, QSAR, molecular docking, ADMET studies

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(E-pub Ahead of Print)
DOI: 10.2174/2211352517666190902130014