Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)Benzenesulfonamide Derivatives

Abstract

A series of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)benzenesulfonamides were synthesized from 4-amino-N-(aryl/heteroaryl)benzenesulfonamides and 2,5-dimethoxytetrahydrofuran. All the synthesized compounds were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. Compound 28, bearing 8-quinolinyl moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 3, 5, and 7 µM, respectively. The apoptotic potential of the most active compound (28) was analyzed through various assays: phosphatidylserine translocation, cell cycle distribution, and caspase activation. Compound 28 promoted cell cycle arrest in G2/M phase in cancer cells, induced caspase activity, and increased the population of apoptotic cells. Relationships between structure and biological activity were determined by the QSAR (quantitative structure activity relationships) method. Analysis of quantitative structure activity relationships allowed us to generate OPLS (Orthogonal Projections to Latent Structure) models with verified predictive ability that point out key molecular descriptors influencing benzenosulfonamide’s activity.

Modeling of Anticancer Sulfonamide Derivatives Lipophilicity by Chemometric and Quantitative Structure-Retention Relationships Approaches

“…The chemical names and SMILES notation of the target sulfonamide derivatives are presented in Table S1, whereas the 2D structures are shown in Figure 8. Their synthesis and characterization were described in the literature [27][28][29][30]. The 1H NMR and 13 C NMR spectra of target molecules are displayed in the Supplementary Materials.…”

“…Broad-spectrum antitumor activity depends on the substituents at the benzene ring of arylsulfonamide and the moieties attached to the nitrogen atom of the sulfonamide group. Recently, pro-apoptotic activity of N-(1,2,4-triazin-3-yl)benzenesulfonamides, N-(5-oxo-1,2,4triazin-3-yl)benzenesulfonamides and N-(heteroaryl)-4-(1H-pyrrol-1-yl)benzenesulfonamides has been proven for human colon cancer (HCT-116) cell [27][28][29]. Apoptosis was confirmed by changes in cell morphology, DNA fragmentation, loss of mitochondrial membrane potential, phosphatidylserine translocation into the outer leaflet of the cell membrane, and activation of caspases [29].…”

Discovery of sulfadrug–pyrrole conjugates as carbonic anhydrase and acetylcholinesterase inhibitors

“…The most active compound in this group was the derivative containing quinoline ring ( P1 ). [ 24 ] Compounds P2 and P3 containing pyrrole and pyrrolo[2,3‐ d ]pyrimidine rings were synthesized by Ghorab et al [ 25 ] and their carbonic anhydrase activities were investigated. Anticancer activities of these compounds were investigated against breast cancer (MCF‐7) cell lines.…”

<p>Discovery of a Novel Benzenesulfonamide Analogue That Inhibits Proliferation and Metastasis Against Ovarian Cancer OVCAR-8 Cells</p>

“…8 Benzenesulfonamide derivative 2 as a histone deacetylase inhibitor has been directed to treat peripheral T-cell lymphoma. 9 In addition, 1,2,3-triazole-based heterocycles have been reported to possess the anticancer activity. 10,11 1,2,3-Triazole 4 could arrest cell cycle at the G0/G1 phase in MCF-7 cells.…”