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Screening ,development of Transglutaminase-2 Inhibitors and its derivative as anti-lung cancer agent by insilico and invitro approach

Author(s):

Prachi P. Parvatikar*, Sumangala Patil, Joy Hoskeri, Sandeep Swargam, Raghvendra Kulkarni and Kusal K Das  

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.

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.

Keywords:

TG2, lung cancer, simulation, molecular interaction, cystamine derivative.

Affiliation:

Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B.M.Patil Medical College, Hospital and Research Centre, Vijayapur-586103, Karnataka, Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B.M.Patil Medical College, Hospital and Research Centre, Vijayapur-586103, Karnataka, Dept of Bioinformatics, Karnataka State Akkamahadevi Women’s University, Vijayapur-586109, Karnataka, Jamia Hamdard Institute of Molecular Medicine (JH-IMM) Lab, Jamia Hamdard University, New Delhi, BLDEA’s Shri SSM Pharmacy college, Vijayapur, Karnataka, Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B.M.Patil Medical College, Hospital and Research Centre, Vijayapur-586103, Karnataka



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