Novel 1H-pyrrolo[2,3-b]pyridine sulfonamide analogues: Design, synthesis, in-vitro anticancer and molecular docking studies

Abstract

In this current article, we have been reported a novel series of 1-(arylsulfonyl)-4-morpholino-1H-pyrrolo[2,3-b]pyridine (6 a-h) and 1-(arylsulfonyl)-4-(4-methylpiperazin-1-yl)-1H-pyrrolo[2,3-b]pyridine (7 a-g). The synthesized compounds were characterized by their 1H-NMR, 13C NMR, LCMS and HRMS spectral data. These compounds were screened for their in-vitro biological studies against two types of cancer cell lines namely, MCF-7 breast cancer cell lines and A549 lung cancer cell line. All the synthesized compounds showed good to moderate cytotoxicity. The activity ranged from the IC50 22.3±0.1 μg/mL to 141.2±0.5 against the breast cancer cell line MCF-7 whereas, the IC50 values ranged 24.4±0.2 μg/mL to >200±0.1 μg/mL with lung cancer cell line A549. Broadly, morpholine-substituted compounds such as 6a-h showed better activity than N-methyl piperazine compounds 7 a-g. The data revealed that compounds 6g and 7f exhibited significant in vitro cytotoxic effects with IC50 values of 22.3±0.1 µg/mL, 31.4±0.5 µg/mL against breast cancer MCF-7 cell line and 24.4±0.2 µg/mL & 36.3±µg/mL against A549 cancer cell line. Furthermore, computational studies were conducted for 6g and 7f using EGFR (PDB ID-4HJO), and compound 6g possessing the high binding energy (-10.83 kcal/mol) due to the establishment of two hydrogen bonds with LYS721 and PHE832 residues. Whereas compound 7f exhibited a good binding energy of -8.60 kcal/mol due to the formation of one hydrogen bond with TYR867. Finally, the molecular properties of the designed compounds were calculated using Swiss ADME software. Many of them obey the rule of 5 with good properties.