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In Silico ADMET and Docking Studies of Thiazolidinedione-acetic-acid Hybrids as Antidiabetics with Cardioprotection

[ Vol. 17 , Issue. 12 ]

Author(s):

Deepanwita Maji, Subir Samanta and Vaishali M. Patil*   Pages 1475 - 1484 ( 10 )

Abstract:


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.

Keywords:

Type 2 diabetes, cardioprotection, toxicity studies, ADME, OSIRIS, ProTox, docking, flexX.

Affiliation:

Department of Pharmaceutical Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, Department of Pharmaceutical Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, Computer Aided Drug Design Lab, KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh

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