Abstract

New series of 10-(2-Styryl-5,6-dihydro-imidazo[2,1-b] [1,3,4] thiadiazole-6-yl)-10H-phenothiazine were synthesized by cyclisation of various carboxylic acid with thiosemicarbazide in presence of sulphuric acid was to get compound 1. Another way phenothiazine treated with chloroacetyl chloride yielded compound 2. Further cyclisation of compound 1 and 2 followed by refluxation about 18 hrs to get the final products 3 and 3a-3i of the series. The structures of compounds were confirmed by IR, 1H-NMR, 13C NMR and mass spectroscopy and by chemical analysis. All the final synthesized compounds 3 and 3a-3i were screened for their antitubercular activity screened against M. tuberculosis H37 Rv. Tuberculosis (TB) is one of the dominant killer diseases [1] and it causes huge amount of human deaths despite the availability of more than 20 anti TB drugs and the Bacille Calmette Guerin (BCG) anti TB vaccine [2]. The emergence of the extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB), against which the traditional anti-TB drugs show limited efficacy,[3] further cause serious problem in TB control. With a population of 1.32 billion, India has the highest burden of tuberculosis (TB) and drug resistant TB (DR-TB) in the world. The Global TB Report 2017 published by World Health Organization (WHO) estimates that India contributes 27% (2.79 million) and 25% (147 000) of the global burden of TB and multi-drug resistant TB (MDR-TB), respectively. The Revised National Tuberculosis Control Programme (RNTCP) has notified 1.94 million patients in 2016. India has been locating and treating MDR-TB patients since 2007 and achieved complete geographical coverage of programmatic management of drug-resistant TB (PMDT) services in 2013 [4]. In the past years, the literature is enriched with progressive finding about the synthesis and pharmacological actions of fused heterocycles [5]. In the field of synthetic organic chemistry nitrogensulphur heteroatom containing aromatic molecules particularly 10-H-phenothiazine and 1,3,4-thiadiazole are becoming more popular as an area of research and provides a most valuable molecular template for the development of new molecule that can interact with a wide variety of biochemical processes. They have been shown to possess a broad spectrum of pharmacological activities such as anti-tubercular [6-7] anti-tumour [8] anti-inflammatory [9] antihyperlipidemic [10], cytotoxic [11], antimicrobial [12] and antiproliferative [13] agents. In continuation in our aim synthesis of new bioactive molecule by incorporating phenothiazine and 1,3,4 heterothiadiazole moieties in a single molecular framework, both molecules have broad biological spectrum such as antibacterial [14,15], antifungal [16,17] anticancer [18,19] anticonvulsant [20,21], antitubercular [22,23] and anti-inflammatory [24,25] herein, we carry out the synthesis and antimicrobial evaluation of some new synthesized molecule. Number of molecules have been claimed by researchers Imidazo [2,1-b]-1,3,4-thiadiazole all around the world because of its excellent biological profile. We have decided to synthesize a new series of 10-(2-Phenyl-imidazo [2,1-b] [1,3,4] thiadiazol-6-yl)-10H-phenothiazine shown in Scheme 1. The starting material, thiosemicarbazide undergoes cyclodehydration of acyl thiosemicarbazides treated with in situ by heating the various carboxylic acid in presence of H2SO4 yielded compound 1, 5-Phenyl-[1,3,4]thiadiazol-2-ylamine. In another separate reaction 10-H phenothiazine treated with chloroacetyl chloride yielded compound 2, 2-Chloro-1-phenothiazin-10-yl-ethanone. Further condensation reaction of compound 2 and compound 1 under reflux in dry ethanol 18 hrs yielded compound 3, 10-(2-Phenylimidazo[ 2,1-b] [1,3,4] thiadiazol-6-yl)-10H-phenothiazine, further compounds (3a-3i) synthesized by similar method as reported earlier. The structure of compounds 1 and (1a-1i), compound 2, and compound 3 and (3a-3i) were confirmed by IR, 1H NMR, 13C NMR, mass and chemical analysis. All the compounds 3 and 3a-3i were screened for their antitubercular activity screened against M. tuberculosis H37 Rv (Scheme 1)

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