Development of water-soluble 3, 5-dinitrophenyl tetrazole and oxadiazole antitubercular agents. Issue 20 (15th October 2017)

• Record Type: Journal Article
• Authors: Roh, Jaroslav; Karabanovich, Galina; Vlčková, Hana; Carazo, Alejandro; Němeček, Jan; Sychra, Pavel; Valášková, Lenka; Pavliš, Oto; Stolaříková, Jiřina; Klimešová, Věra; Vávrová, Kateřina; Pávek, Petr; Hrabálek, Alexandr
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 20(2017)
• Page Start: 5468
• Page End: 5476
• Publication Date: 2017-10-15
• Subjects: Tuberculosis -- Antitubercular agent -- Mycobacterium tuberculosis -- Structure-activity relationships -- Lipophilicity -- Solubility; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.08.010
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: In this work, four series of tertiary amine-containing derivatives of 3, 5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. We found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. The N -benzylpiperazine derivatives, which had the highest lipophilicity among all of the series, showed the highest in vitro antimycobacterial activities against Mycobacterium tuberculosis CNCTC My 331/88 (H37 Rv), comparable to those of the first-line drugs isoniazid and rifampicin. The presence of two tertiary amines in these N -benzylpiperazine derivatives enabled us to prepare water-soluble dihydrochloride salts, overcoming the serious drawback of previously described 3, 5-dinitrophenyl tetrazole and oxadiazole lead compounds. The water-soluble 3, 5-dinitrophenyl tetrazole and oxadiazole antitubercular agents described in this work are good candidates for further in vitro and in vivo pharmacokinetic and pharmacodynamic studies.