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.

背景：2型糖尿病与许多影响重要身体器官（尤其是心脏）的副作用有关。噻唑烷二酮是有效的抗糖尿病药。研究证明氨基酸和多肽可促进葡萄糖转运，具有抗氧化特性，并且副作用较少，因此我们通过将氨基酸酯和肽酯与2、4噻唑烷二酮乙酸部分（可作为抗糖尿病药）结合使用来设计杂种心脏保护特性。

方法：分别使用Qikprop3.1.OSIRIS，PROTOX（啮齿动物口腔毒性预测）和FlexX 2.1.3进行了体外ADME，毒性和对接研究。

结果：所有设计的分子均属于三个亚系列，分别为2，2，4-二氧噻唑烷-5-乙酸单氨基酸杂合甲酯，2，4-4-二氧噻唑烷-5-乙酸二肽杂合甲酯和2，4，二氧噻唑烷-5-乙酸三肽杂合甲基酯。所有分子都是无毒的。SSMA2，SSMA14，SSMA49和SSDM50分别在2PRG和2UV4中显示了良好的对接得分。

结论：选定的计算机模拟研究有助于设计具有较低毒性，目标特异性和双重活性的杂种，作为潜在的抗糖尿病和心脏保护剂。