Tetrazole regioisomers in the development of nitro group-containing antitubercular agents. Issue 1 (24th October 2014)

• Record Type: Journal Article
• Authors: Karabanovich, Galina; Roh, Jaroslav; Soukup, Ondřej; Pávková, Ivona; Pasdiorová, Markéta; Tambor, Vojtěch; Stolaříková, Jiřina; Vejsová, Marcela; Vávrová, Kateřina; Klimešová, Věra; Hrabálek, Alexandr
• Is Part Of: MedChemComm. Volume 6:Issue 1(2015:Jan.)
• Page Start: 174
• Page End: 181
• Publication Date: 2014-10-24
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c4md00301b
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Tetrazole derivatives containing nitro substituents have been identified as promising antitubercular agents. Abstract : Tetrazole derivatives containing nitro substituents have been identified as promising antitubercular agents. In this study, the antitubercular potency, selectivity and toxicity of tetrazole 1, 5- and 2, 5-regioisomers were examined. We prepared a series of 1- and 2-alkyl-5-benzylsulfanyl-2 H -tetrazoles and their selenium analogs with various nitro group substitutions. These 1, 5- and 2, 5-regioisomers were isolated and unambiguously identified using 1 H and/or 13 C NMR. Among the prepared compounds, 1- and 2-alkyl-5-[(3, 5-dinitrobenzyl)sulfanyl]-2 H -tetrazole derivatives and their selenium bioisosteres showed the highest antimycobacterial activity, with minimal inhibitory concentration (MIC) values of approximately 1 μM (0.37–0.46 μg mL −1 ) against Mycobacterium tuberculosis CNCTC My 331/88. The 2-alkyl regioisomers exhibited consistently higher antimycobacterial activity and lower in vitro toxicity against a mammalian cell line compared to the 1-alkyl isomers. The antimycobacterial activity of the 2-alkyl regioisomers was less influenced by the type of alkyl substituent in contrast to 1-alkyl isomers. Furthermore, the 3, 5-dinitrobenzyl moiety per se is not the carrier of mutagenicity. These findings encourage further optimization of the 2-alkyl chain to improve the pharmacokinetic properties and toxicity of 2-alkyl-5-[(3, 5-dinitrobenzyl)sulfanyl]-2 H -tetrazole lead compounds.