Synthesis and anti-tubercular activity of 3-substituted benzo[b]thiophene-1,1-dioxides
نویسندگان
چکیده
We demonstrated that the 3-substituted benzothiophene-1,1-dioxide class of compounds are effective inhibitors of Mycobacterium tuberculosis growth under aerobic conditions. We examined substitution at the C-3 position of the benzothiophene-1,1-dioxide series systematically to delineate structure-activity relationships influencing potency and cytotoxicity. Compounds were tested for inhibitory activity against virulent M. tuberculosis and eukaryotic cells. The tetrazole substituent was most potent, with a minimum inhibitory concentration (MIC) of 2.6 µM. However, cytotoxicity was noted with even more potency (Vero cell TC50 = 0.1 µM). Oxadiazoles had good anti-tubercular activity (MICs of 3-8 µM), but imidazoles, thiadiazoles and thiazoles had little activity. Cytotoxicity did not track with anti-tubercular activity, suggesting different targets or mode of action between bacterial and eukaryotic cells. However, we were unable to derive analogs without cytotoxicity; all compounds synthesized were cytotoxic (TC50 of 0.1-5 µM). We conclude that cytotoxicity is a liability in this series precluding it from further development. However, the series has potent anti-tubercular activity and future efforts towards identifying the mode of action could result in the identification of novel drug targets.
منابع مشابه
Synthesis and anti - tubercular activity of 3 - substituted benzo [ b ] thiophene - 1 , 1 -
متن کامل
Synthesis of some New Thiosemicarbazide and 1,3,4-Thiadiazole Heterocycles Bearing Benzo[b]Thiophene Nucleus as a Potent Antitubercular and Antimicrobial Agents
Reaction of 2-hydrazinocarbonyl-3-chloro-5-phenoxy-benzo[b] thiophene with different substituted phenyl isothiocyanate gave N-substituted arylthiosemi-carbazide derivatives (1a-h). 1,3,4-Thiadiazole derivatives (2a-h) were prepared by the cyclization of arylthiosemicarbazides (1a-h) with concentrated sulphuric acid. All the compounds were screened for their antitubercular activity against Mycob...
متن کاملSynthesis of some New Imidazolones and 1,2,4-Triazoles Bearing Benzo[b]thiophene Nucleus as Antimicrobial Agents
2-Phenyl-1-(3?,5?-dichloro-2?-benzo(b)thiophenoylamino)-4-arylidine-5-imidazolones (2a-j) were prepared from the 2-hydrazinocarbonyl-3,5-dichlorobenzo[b]thiophene 1 by the reaction with different oxazolinone which were prepared by the condensation of substituted benzaldehyde with benzoyl glycine in presence of sodium acetate and acetic anhydride. Reaction of 1 with different aromatic isothiocya...
متن کاملSynthesis and biological activity of novel 3-heteroaryl-2H-pyrido[4,3-e][1,2,4]thiadiazine and 3-heteroaryl-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxides
ABSTRACT A series of novel 1,2,4-thiadiazine 1,1-dioxides were synthesized by condensation of 2-chlorobenzenesulfonamide and 4-chloropyridine-3-sulfonamide with heterocyclic methyl carbimidates obtained from heterocyclic carbonitriles and used at the time of their creation. Substituted amidines were isolated as the intermediates in the reaction with 2-chlorobenzenesulfonamide. Those intermediat...
متن کاملSynthesis of 2-substituted benzo[b]thiophene via a Pd-catalyzed coupling of 2-iodothiophenol with phenylacetylene
A Pd(II)-catalyzed Sonogashira type cross-coupling reaction between 2-iodothiophenol and phenylacetylene has been developed. A series of 2-substituted benzo[b]thiophenes were obtained in moderate to good yield (up to 87%). The application of this method was demonstrated by the synthesis of 2-(4-(tert-butyl)phenyl)benzo[b]thiophene 1,1-dioxide and (4-methoxyphenyl)(2-(4-methoxyphenyl) benzo[b]th...
متن کامل