Synthesis, molecular docking and biological evaluation of novel 6-(4-(4-aminophenylsulfonyl)phenylamino)-5H-benzo[a]phenothiazin-5-one derivatives

•The compound 1 synthesized by a green route using water as solvent.•The final compounds (3a–n) were obtained in better yield of about 93–94%.•Most of the compounds exhibited better antibacterial properties.•Compound 3a and 3n exhibits better cytotoxicity against cervical cancer cell line (SiHa).•Compound 3n exhibited better antibacterial property in a concentration of 0.4 μg/mL against Bacillus subtilis.

A novel series of 6-(4-(4-aminophenylsulfonyl)phenylamino)-5H-benzo[a]phenothiazin-5-one derivatives have been synthesized and examined for their in vitro antibacterial activity against a panel of Gram-positive and Gram-negative bacteria. Among these, N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6-ylamino)phenylsulfonyl)phenyl)-3,5-bis(trifluoromethyl)benzamide (3n) (0.4 μg/mL) and 4-ethyl-N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6-ylamino)phenylsulfonyl)phenyl)benzamide (3l) (0.6 μg/mL) systems exhibited a potent inhibitory activity against Gram-positive organism Bacillus subtilis, when compare to the other synthesized compounds. Sparfloxacin (9.76 μg/mL), Norfloxacin (no activity) were employed as the standard drugs. An evaluation of the cytotoxicity of the title compounds (1, 2, 3a–n) revealed that they displayed low toxicity (26–115 mg/L) against cervical cancer cell line (SiHa). The results of these studies suggest that, phenothiazin-5-one derivatives are interesting binding agents for the development of new Gram-positive and Gram-negative antibacterial agents. To understand the interactions with protein receptors, docking simulation was done with crystal structures of B.subtilis (YmaH) and histone deacetylase (HDAC8) to determine the probable binding conformation.

Graphical abstractEqual mole concentrations of starting materials gave the final products in multistep reactions. The compound 3a (IC50 = 26 μg/mL) act as a better anticancer agent and compound 3n (IC50 = 32 μg/mL & MIC = 0.4 μg/mL) plays a dual role as better anticancer and antibacterial agent.Figure optionsDownload full-size imageDownload as PowerPoint slide