2. Academic Validation
  3. Synthesis and antituberculosis activity of indole-pyridine derived hydrazides, hydrazide-hydrazones, and thiosemicarbazones

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

  • Bioorg Med Chem Lett. 2016 Feb 1;26(3):978-985. doi: 10.1016/j.bmcl.2015.12.049.
Valeriya Velezheva 1,  Patrick Brennan 2,  Pavel Ivanov 1,  Albert Kornienko 1,  Sergey Lyubimov 1,  Konstantin Kazarian 3,  Boris Nikonenko 3,  Konstantin Majorov 3,  Alexander Apt 3
Affiliations

Affiliations

  • 1 A.N.Nesmeyanov Institute of Organoelement Compounds Russian Academy of Sciences, 28 Vavilov Str., 117813 Moscow, Russia.
  • 2 Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682 USA.
  • 3 Central TB Research Institute Russian Academy of Medical Sciences, 2, Yauzskaya Alley, 107564 Moscow, Russia.
PMID: 26725953 DOI: 10.1016/j.bmcl.2015.12.049
Abstract

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 C-N or double C=N 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 (0.05-2 μg/mL). Five compounds demonstrated appreciable activity against the INH-resistant M. tuberculosis CN-40 clinical isolate (MICs: 2-5 μg/mL), providing justification for further in vivo studies.

Keywords

Anti-tuberculosis compounds; Hydrazide–hydrazones; Indole–pyridine derived hydrazides; Thiosemicarbazones.

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