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Current Computer-Aided Drug Design

Editor-in-Chief

ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

Research Article

Screening and Development of Transglutaminase-2 Inhibitors and their Derivative as Anti-lung Cancer Agent by in silico and in vitro Approaches

Author(s): Prachi P. Parvatikar*, Sumangala Patil, Joy Hoskeri, Sandeep Swargam, Raghvendra V. Kulkarni and Kusal K Das

Volume 18 , Issue 1 , 2022

Published on: 22 March, 2021

Page: [41 - 51] Pages: 11

DOI: 10.2174/1573409917666210322120350

Abstract

Aim: This study aimed at screening and development of TG2 inhibitors as anti lung cancer agent.

Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from the transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative diseases, and also cancer.

Objective: The proposed study focused on screening potent inhibitors of TG2 by in-silico method and synthesize their derivative as well as analyse its activity by utilizing an in-vitro approach.

Materials and Methods: Molecular docking studies have been carried out on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction while possessing the least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines using cytotoxicity studies.

Results: The results of the present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein, so this derivative of cystamine was formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecules proved to be good cytotoxic agents against A549 lung cancer (875.10, 553.22 μg/ml), respectively. Further, their activity needs to be validated on TG2 expressing lung cancer.

Conclusion: Cystamine and its derivative can act as a potential therapeutic target for lung cancer but its activity should be further validated on TG2 expressing lung cancer.

Keywords: TG2, lung cancer, simulation, molecular interaction, cystamine derivative, molecular docking

Graphical Abstract

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