Design and Synthesis of Thiazole Scaffold-Based Small Molecules as Anticancer Agents Targeting the Human Lactate Dehydrogenase A Enzyme.

ABSTRACT: A new series of thiazole central scaffold-based small molecules of hLDHA inhibitors were designed using an in silico approach. Molecular docking analysis of designed molecules with hLDHA (PDB ID: 1I10) demonstrates that Ala 29, Val 30, Arg 98, Gln 99, Gly 96, and Thr 94 possessed strong interaction with the compounds. Compounds 8a, 8b, and 8d showed good binding affinity (-8.1 to -8.8 kcal/mol), whereas an additional interaction of NO₂ at the ortho position in compounds 8c with Gln 99 through hydrogen bonding enhanced the affinity to -9.8 kcal/mol. Selected high-scored compounds were synthesized and screened for hLDHA inhibitory activities and in vitro anticancer activity in six cancer cell lines. Biochemical enzyme

SUBMITTER: Sharma D 

PROVIDER: S-EPMC10210175 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature