title: Synthesis and antituberculosis activity of indole-pyridine derived hydrazides, hydrazide-hydrazones, and thiosemicarbazones.
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.
authors.affiliation: A.N.Nesmeyanov Institute of Organoelement Compounds Russian Academy of Sciences, 28 Vavilov Str., 117813 Moscow, Russia.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Velezheva
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682 USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brennan
authors.affiliation: A.N.Nesmeyanov Institute of Organoelement Compounds Russian Academy of Sciences, 28 Vavilov Str., 117813 Moscow, Russia.
authors.forename: Pavel
authors.initials: P
authors.lastname: Ivanov
authors.affiliation: A.N.Nesmeyanov Institute of Organoelement Compounds Russian Academy of Sciences, 28 Vavilov Str., 117813 Moscow, Russia.
authors.forename: Albert
authors.initials: A
authors.lastname: Kornienko
authors.affiliation: A.N.Nesmeyanov Institute of Organoelement Compounds Russian Academy of Sciences, 28 Vavilov Str., 117813 Moscow, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Lyubimov
authors.affiliation: Central TB Research Institute Russian Academy of Medical Sciences, 2, Yauzskaya Alley, 107564 Moscow, Russia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kazarian
authors.affiliation: Central TB Research Institute Russian Academy of Medical Sciences, 2, Yauzskaya Alley, 107564 Moscow, Russia.
authors.forename: Boris
authors.initials: B
authors.lastname: Nikonenko
authors.affiliation: Central TB Research Institute Russian Academy of Medical Sciences, 2, Yauzskaya Alley, 107564 Moscow, Russia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Majorov
authors.affiliation: Central TB Research Institute Russian Academy of Medical Sciences, 2, Yauzskaya Alley, 107564 Moscow, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Apt
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D006834:Hydrazines / Q000737:chemistry*; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D006834:Hydrazines; D006835:Hydrazones; D007211:Indoles; D011725:Pyridines; D013882:Thiosemicarbazones; C029424:hydrazine; C012381:indole-3-carbaldehyde; C030374:indole; C023666:pyridine
keywords: Anti-tuberculosis compounds; Hydrazide–hydrazones; Indole–pyridine derived hydrazides; Thiosemicarbazones