Mechanistic Approach into 1,2,3-triazoles-based IIIM(S)-RS98 Mediated Apoptosis in Lung Cancer Cells.

Abstract

Lung cancer is a major public health problem across the globe, since it is the second most frequent cancer and the leading cause of cancer fatalities. This necessitates careful assessment of current therapies for lung cancer and discovery of novel drug candidates. 1,2,3 triazole compounds have emerged as an important class of prospective chemotherapeutic drugs for the treatment of lung cancer, with promising anti-lung cancer activity shown via a variety of pathways. They may interact with a various enzymes and receptors in cancer cells, causing cell cycle arrest and the activation of apoptosis. The present study aims to investigate the cytotoxic potential of institutional molecule based on 1,2,3 triazole [IIIM(S)-RS98] on multiple cancer cell lines. The compound was found to be most active on A549 cells and displayed the selectivity index as 8.16 in normal cells (e.g. HEK293). The in vitro findings revealed that IIIM(S)-RS98 induced apoptosis, loss of mitochondrial membrane potential, enhanced ROS and nitric oxide levels, and arrest cells in the G1 phase of the cell cycle. It inhibits the cell migration and clonogenic potential of A549 cells. Additionally, the downregulation of PI3K and p-Akt pathway leads to the activation of pro-apoptotic proteins Bax, downregulation of bcl2, activation of caspase 9, cleaved caspase 3, and cleaved parp1 expression and finally contribute towards apoptosis. Furthermore, molecular docking analysis indicated the interactions of IIIM(S)-RS98 with the apoptotic target proteins. The results demonstrated the potential of IIIM(S)-RS98 in the therapy of lung cancer.