Spectrochim Acta A Mol Biomol Spectrosc. 2015 Mar 15;139:477-87. doi: 10.1016/j.saa.2014.12.036. Epub 2014 Dec 19.

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

Ravichandiran P¹, Athinarayanan J², Premnath D³, Periasamy VS⁴, Alshatwi AA⁴, Vasanthkumar S⁵.

Author information

1: Department of Chemistry, School of Science & Humanities, Karunya University, Coimbatore 641 114, India. Electronic address: ravichandru55@gmail.com.
2: Department of Nanosciences & Technology, School of Nanosciences & Technology, Karunya University, Coimbatore 641 114, India; Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Sciences and Agriculture, King Saud University, P.O. Box 2460, Riyadh 11451, Kingdom of Saudi Arabia.
3: Department of Bioinformatics, School of Biotechnology and Health Sciences, Karunya University, Coimbatore 641 114, India.
4: Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Sciences and Agriculture, King Saud University, P.O. Box 2460, Riyadh 11451, Kingdom of Saudi Arabia.
5: Department of Chemistry, School of Science & Humanities, Karunya University, Coimbatore 641 114, India. Electronic address: kumar2359@yahoo.com.

Abstract

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.