1618101-10-2Relevant articles and documents
Tetrazole regioisomers in the development of nitro group-containing antitubercular agents
Karabanovich, Galina,Roh, Jaroslav,Soukup, Ondej,Pvkov, Ivona,Pasdiorov, Markta,Tambor, Vojtch,Stolakov, Jiina,Vejsov, Marcela,Vvrov, Kateina,Klimeov, Vra,Hrablek, Alexandr
supporting information, p. 174 - 181 (2015/02/02)
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-2H-tetrazoles and their selenium analogs with various nitro group substitutions. These 1,5- and 2,5-regioisomers were isolated and unambiguously identified using 1H and/or 13C NMR. Among the prepared compounds, 1- and 2-alkyl-5-[(3,5-dinitrobenzyl)sulfanyl]-2H-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]-2H-tetrazole lead compounds. This journal is
