Synthesis and Biological Evaluation of Some Novel Substituted N-Benzylideneaniline Derivatives

ABSTRACT N-benzylideneaniline is a class of important compounds in medicinal and pharmaceutical field. Nbenzylideneaniline represents a model aromatic Schiff base and it is also a classic bioisoster of stilbene and resveratrol. Keeping in view the biological importance of N-benzylideneaniline we have synthesized some novel Nbenzylideneaniline derivatives. The prepared compounds were tested for their in vitro antibacterial, antifungal and antioxidant activity. (4-fluoro-benzylidene)-(3,5-dichloro-phenyl)-amine (5i) showed in vitro antibacterial activity comparable to that of the standard Penicillin against Escherichia coli. The results of the in vitro antifungal activity showed that most of the synthesized derivatives have proven their antifungal potential. The results of the in vitro antioxidant tests showed that most of the synthesized compounds showed moderate (%RSA >50%) to mild (%RSA >40%) radical scavenging activity

Benzothiazinone-piperazine derivatives as efficient Mycobacterium tuberculosis DNA gyrase inhibitors

Background and objectives: Bacterial DNA topoisomerases are unique in maintaining the DNA topology for cell viability. Mycobacterium tuberculosis (MTB) DNA gyrase, a sole type II topoisomerase has a larger scope as a target for developing novel therapeutics. In this study, an effort was made towards the design and synthesis of benzothiazinone-piperazine hybrid analogues to obtain the possibility of it to lead development through the molecular hybridization technique. Methods: A five-step scheme was followed to obtain a series of 36 benzothiazinone-piperazine derivatives and to evaluate them for Mtb DNA gyrase inhibition, antimycobacterial and cytotoxicity studies. Results: Compound N-(4-chlorophenyl)-4-(6-nitro-4-oxo-4H-benzo[e][1,3]thiazin-2-yl)piperazine-1-carbothioamide (18) showed greater inhibitory potential with an IC50 of 0.51±0.16 μM in the DNA supercoiling assay of Mtb with a moderate anti-tubercular activity of 4.41 μM. The compound even passed the safety profile of eukaryotic cell cytotoxicity with a 1.81% inhibition in the RAW 264.7 cell line at 100 μM concentration. Conclusions: This study describes the discovery of benzothiazinone as gyrase inhibitors with potent Mtb MIC and inhibitory profiles of the gyrase enzyme with less cytotoxic effect. Furthermore, it is believed that this class of compounds has the potential to be further developed as an anti-TB drug candidate