Design, Synthesis, in Silico Molecular Docking and ADMET Studies of Indole‐Sulfonamide Derivatives as Tubulin Polymerization Inhibiting Agents

Abstract In this paper, we describe the synthesis of indolyl aryl sulfonamide conjugates ( 6 a – n ). The anti‐tumour activity was assessed on three human cancer cell lines: A‐549 (lung), HeLa (cervix), and MCF‐7 (breast). Nocodazole was used as a standard drug by employing the MTT assay method. The results show that the compounds 6 b , 6 l , and 6 m have shown more potent activity as compared to the standard drug Nocodazole. In a cell survivability test (MCF‐10 A), three potent compounds ( 6 b , 6 l , and 6 m ) were evaluated against the normal breast cell line, although neither of them displayed any significant cytotoxicity with IC 50 values greater than 78.45 μM. Furthermore, the compounds 6 b , 6 l , and 6 m were tested for tyrosine kinase EGFR inhibitory action using Combretastatin A‐4 as the reference drug. The in vitro tubulin polymerization inhibitory activity indicates that the compounds 6b and 6 l showed promising potency with IC 50 values of 2.40±0.02 and 2.34±0.03 mM, respectively. In addition to this, molecular docking studies of compounds 6 b , 6 l , and 6 m demonstrated that these compounds had more EGFR binding interactions. The potent compounds 6 b , 6 l , and 6 m were subjected to in silico pharmacokinetic assessment by SWISS, ADME, and pkCSM. While the compounds 6 b , 6 l , and 6 m followed five filters (Lipinski rule, Ghose rule, Veber rule, Egan rule, and Muegge rule) without any deviation.