Background: Type-2-diabetes mellitus is associated with many side effects affecting vital
body organs, especially heart. Thiazolidinediones are potent antidiabetics. Studies have proven
that amino-acids and peptides promote glucose transport, have antioxidant properties, and fewer side effects,
thus we designed hybrids by combining amino-acid esters and peptide esters with 2, 4
thiazolidinedione acetic acid moiety which can act as antidiabetic agent with cardioprotection properties.
Methodology: In vitro ADME, toxicity, and docking studies were performed using
Qikprop3.1.OSIRIS, PROTOX (Prediction of Rodent Oral Toxicity), and FlexX 2.1.3, respectively.
Results: All the designed molecules belong to three sub-series, i.e. 2, 4-dioxothiazolidine-5-acetic
acid single amino acid hybrid methyl esters, 2, 4-dioxothiazolidine-5-acetic acid dipeptide hybrid
methyl esters and 2, 4-dioxothiazolidine-5-acetic acid tripeptide hybrid methyl esters. All molecules
were non-toxic. SSMA2, SSMA14, SSMA49, and SSDM50 showed good docking scores in 2PRG
and 2UV4, respectively.
Conclusion: The selected in silico studies helped to design hybrids with less toxicity, target specificity
with dual activity as potential anti-diabetic and cardioprotective agents.