In-vitro and in-silico study to assess anti breast cancer potential of N-tosyl-indole based hydrazones
Uzma Ghaffar, Faizullah Khan, Javid Hussain, Suraj N. Mali, Ajmal Khan, Somdatta Y. Chaudhari, Rahul D. Jawarkar, Abdullah K. Alanazi, Waseem Ul Islam, Mostafa A. Ismail, Ahmed Al‐Harrasi, Zahid Shafiq
Abstract
The main objective of research worldwide is targeting particular genes and proteins vital for the development and viability of cancer cells. This recent research explores the synthesis and biological evaluation of N-tosyl indole-3-carbaldehyde based hydrazones 5(a-r) as anti-breast cancer (BC) agents. Two cell lines were employed to evaluate newly synthesized compounds in-vitro; the normal epithelial breast cell line MCF-10 A and the MDA-MB-231 BC cell line. All the synthesized compounds demonstrated significant activity against the BC cell line MDA-MB-231. Compound 5p (IC50 = 12.2 ± 0.4 µM) with a naphthyl group, exhibited promising potential against triple-negative breast cancer (TNBC) cell line MDA-MB-231. The structures of the compounds 5(a-r) were confirmed by using different characterization techniques such as FT-IR, ¹H NMR, ¹³C NMR, and QTOF HRMS. Molecular docking study demonstrates that compound 5q binds strongly to EGFR (T790M/L858R mutant) with binding energy − 11.533 kcal/mol. However, molecular dynamics show stable interactions with protein 3W2S over 100 ns, supported by favorable RMSD, RMSF and SASA values. These findings hypothesize that compound 5q exerts its anticancer effect through stable molecular interactions. All synthesized compounds significantly reduced viability in MDA-MB-231 cells compared to normal MCF-10 A cells (p < 0.0001), indicating selective cytotoxicity toward breast cancer cells.