Design, synthesis, biological evaluations and in silico studies of (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/arylsulfonates as potential α-glucosidase inhibitors

Lalita Dahiya; Jatin Jangra; Sunil Kumar; Rajiv Kumar; Rajnish Kumar; Sandip V Pawar; Ashok Kumar Yadav

doi:10.1016/j.bioorg.2024.108027

Design, synthesis, biological evaluations and in silico studies of (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/arylsulfonates as potential α-glucosidase inhibitors

Bioorg Chem. 2024 Dec 4:154:108027. doi: 10.1016/j.bioorg.2024.108027. Online ahead of print.

Authors

Lalita Dahiya¹, Jatin Jangra², Sunil Kumar³, Rajiv Kumar³, Rajnish Kumar², Sandip V Pawar³, Ashok Kumar Yadav⁴

Affiliations

¹ University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India; Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119, India.
² Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (B.H.U.), Varanasi 221005, U.P., India.
³ University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
⁴ University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: ashoky@pu.ac.in.

PMID: 39657548
DOI: 10.1016/j.bioorg.2024.108027

Abstract

Diabetes mellitus is considered one of the major worldwide health emergencies of the twenty-first century. This work described development, synthesis, and characterization of new (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/aryl-sulfonates. Compounds 7j and 7m were shown to be the most potent among the newly developed (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/aryl-sulfonates after in vitro testing for α-glucosidase inhibitory activity. Following that, an in-vivo disaccharide loading test was performed on these compounds. From the cytotoxicity studies, the most potent substance (7m) was also founded non-toxic. To investigate the binding mechanism and important interactions of α-glucosidase's amino acid residues, docking analyses were completed and binding affinities of the synthesised compounds were observed from -7.1 to 9.6 kcal/mol. To determine the binding stability of the α-glucosidase protein with chemicals 7j and 7m, molecular dynamic simulations were employed. In silico research and prediction studies for absorption, distribution, metabolism, and excretion (ADME) were used to identify the "druggable" pharmacokinetic profiles. In this instance, we developed unique (Z)-2-(2,4-dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/aryl-sulfonates as α-glucosidase inhibitors.

Keywords: (Z)-2-(2,4-Dioxothiazolidin-5-ylidene)methyl)-2-ethoxyphenyl-alkyl/aryl-sulfonates; Biological evaluation; Diabetes mellitus; Synthesis; α-Glucosidase inhibitors.