Design, Synthesis, and Evaluation of EA-Sulfonamides and Indazole-Sulfonamides as Promising Anticancer Agents: Molecular Docking, ADME Prediction, and Molecular Dynamics Simulations.

Saghdani, Nassima; El Brahmi, Nabil; El Abbouchi, Abdelmoula; Haloui, Rachid; Elkhattabi, Souad; Guillaumet, Gérald; El Kazzouli, Saïd

New EA-sulfonamides and indazole-sulfonamides were synthesized, characterized, and evaluated for their anticancer activities. The target compound structures were elucidated using various spectroscopic techniques such as NMR-{1H and 13C}, infrared spectroscopy, and high-resolution mass spectrometry. The anticancer activities of the novel compounds were evaluated against four human cancer cell lines, namely A-549, MCF-7, Hs-683, and SK-MEL-28 as well as the normal cell line HaCaT, using 5-fluorouracil and etoposide as reference drugs. Among the tested compounds, 9, 10, and 13 exhibited potent anticancer activities which are better than or similar to the reference compounds 5-fluorouracil and etoposide, against the A-549, MCF-7, and Hs-683 cancer cell lines, with IC50 values ranging from 0.1 to 1 μM. Molecular docking studies of compounds 9, 10, and 13 showed a strong binding with selected protein kinase targets, which are linked to the tested cancer types. Furthermore, the analysis of the molecular dynamics simulation results demonstrated that compound 9 exhibits significant stability when bound to both JAK3 and ROCK1 kinases. This new compound has the potential to be developed as a novel therapeutic agent against various cancers.

MOLECULAR dynamics; PROTEIN kinases; ANTINEOPLASTIC agents; MOLECULAR docking; CARRIER proteins

Chemistry (2624-8549), 2024, Vol 6, Issue 6, p1396

2624-8549

Academic Journal

10.3390/chemistry6060083