Structure-based design, synthesis and biological evaluation of N-substituted 6H-thiochromeno[2,3–c]quinolin-12(12H)-one as potential breast cancer drugs
Journal
Arabian Journal of Chemistry
Journal Volume
17
Journal Issue
1
Pages
105423
Date Issued
2024-01-01
Author(s)
Sumitra, Maryam Rachmawati
Chen, Lung Ching
Tsai, Wei Chen
Ansar, Muhamad
Lawal, Bashir
Mokgautsi, Ntlotlang
Wu, Alexander T.H.
Huang, Hsu Shan
Abstract
Tetraheterocyclic compounds, derived from natural sources and contemporary pharmaceuticals, have shown promise as multitarget therapeutic agents. However, their mechanisms of action remain partially understood. In this study, we synthesized a series of 6H-thiochromeno[2,3-c]quinolin-12(12H)-one derivative, totaling 26 compounds, and assessed their potential for therapeutic application. We evaluated their effects on cell proliferation and conducted NCI-60 cell panel assays. MTT assays revealed that select compounds exhibited notable antiproliferative activity against two breast cancer cell lines (MCF-7 and MDA-MB-468). Notably, compounds 17 and 18 displayed the highest cytotoxicity against these cell lines. Furthermore, one-dose assays of the NCI-60 human tumor cell line screening program identified compounds 6, 7, 16, 18, 20, 24, 25, and 30 for further investigation. Subsequent five-dose cytotoxicity studies focused on compounds 18 and 20, which met the threshold inhibition criteria across a panel of cell lines. Our study highlights the effectiveness of compounds 18 and 20 in targeting breast cancer cell lines. Molecular docking simulations revealed that these compounds bind to the active sites of topoisomerase I (TOPO I). Our findings suggest that these novel compounds are promising anticancer agents, particularly against breast cancer, and are worthy of consideration as lead pharmacological candidates.
Subjects
Breast cancer | Molecular docking | NCI 60-cell panel assay | Tetraheterocyclic
SDGs
Type
journal article