Synthesis and antituberculosis activity of indole–pyridine derived hydrazides, hydrazide–hydrazones, and thiosemicarbazones

• Published in: Bioorganic & medicinal chemistry letters 2016-02, Vol.26 (3), p.978-985
• Main Authors: Velezheva, Valeriya, Brennan, Patrick, Ivanov, Pavel, Kornienko, Albert, Lyubimov, Sergey, Kazarian, Konstantin, Nikonenko, Boris, Majorov, Konstantin, Apt, Alexander
• Format: Article
• Language: English
• Subjects: Anti-tuberculosis compounds; Antitubercular Agents - chemical synthesis; Antitubercular Agents - pharmacology; Drug Resistance, Bacterial - drug effects; Hydrazide–hydrazones; Hydrazines - chemistry; Hydrazones - chemical synthesis; Hydrazones - chemistry; Hydrazones - pharmacology; Indoles - chemistry; Indole–pyridine derived hydrazides; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Pyridines - chemistry; Structure-Activity Relationship; Thiosemicarbazones; Thiosemicarbazones - chemical synthesis; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.12.049

[Display omitted] We describe the design, synthesis, and in vitro antimycobacterial activity of a series of novel simple hybrid hydrazides and hydrazide–hydrazones combining indole and pyridine nuclei. The compounds are derivatives of 1-acetylindoxyl or substituted indole-3-carboxaldehydes tethered via a hydrazine group by simple CN or double CN bonds with 3- and 4-pyridines, 1-oxide 3- and 4-pyridine carbohydrazides. The most active of 15 compounds showed MICs values against an INH-sensitive strain of Mycobacterium tuberculosis H37Rv equal to that of INH (0.05–2μg/mL). Five compounds demonstrated appreciable activity against the INH-resistant M. tuberculosis CN-40 clinical isolate (MICs: 2–5μg/mL), providing justification for further in vivo studies.