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

Abstract

Aim: Screening and development of TG2 inhibitors as anti lung cancer agent. Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer. Background: Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative and also cancer. Objective : The of proposed study is to focused on screening of potent inhibitors of TG2 by in-silico method and synthesis its derivative as well as analysis of its activity by invitro approach. Material and Methods: Molecular docking studies have been carried 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 with possessing least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines by cytotoxicity studies. Results: The results of present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein so, this derivative of cystamine is formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecule proved good cytotoxic agent against A549 lung cancer (875.10, 553.22 µg/ml) respectively. Further its activity should be validated on TG2 expressing lung cancer. Conclusion : Cystamine and its derivative can be act as potential therapeutic target for lung cancer but further its activity should be validated on TG2 expressing lung cancer.

A multi-model study of extracellular vesicles in bowel cancer invasion and metastasis

“…For these reasons, TG2 is now considered a crucial player in all the hallmarks of cancer. In the most recent years, research on TG2 activity in cancer has been focussed on the role in chemotherapy resistance and in the development of TG2 inhibitors as anti-cancer agents (Eckert, 2019;Parvatikar et al, 2022;Shinde et al, 2022). However, due to its multifunctional properties and heterogeneous activity, the modulation of TG2 cannot lead to a single solution for treatment of all cancers.…”