Title:Screening and Development of Transglutaminase-2 Inhibitors and their Derivative as Anti-lung Cancer Agent by in silico and in vitro Approaches
VOLUME: 17
Author(s):Prachi P. Parvatikar*, Sumangala Patil, Joy Hoskeri, Sandeep Swargam, Raghvendra Kulkarni and Kusal K Das
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
Keywords:TG2, lung cancer, simulation, molecular interaction, cystamine derivative, molecular docking.
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.
