title: Novel pyridazino[4,3-b]indoles with dual inhibitory activity against Mycobacterium tuberculosis and monoamine oxidase.
abstract: Tuberculosis is one of the most common infectious diseases known to man. About 37% of the world's population (about 1.86 billion people) are infected with Mycobacterium tuberculosis. According to the World Health Organization, every year approximately 8 million people develop active tuberculosis and almost 2 million of those die from the disease. The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing. The present drug regimen for treating tuberculosis has been in existence for 30 years. New drugs that will shorten total treatment duration, improve the treatment of MDR-TB, and address latent tuberculosis are the most urgent need of tuberculosis control programs. A new series of synthetic 3-amino-4-arylpyridazino[4,3-b]indoles (pyridazinoindoles) were identified as inhibitors of Mycobacterium tuberculosis. The design, synthesis, and antimycobacterial activity of these compounds are described. While the most active compounds are still not comparable to the front-line drugs rifampicin and isoniazid, they do show promise. Most of the pyridazinoindoles with appreciable antituberculosis activity also inhibit monoamine oxidase, suggestive of a novel inhibitory effect on mycobacterial redox reactions.
authors.affiliation: A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov Street, 119991 Moscow, Russia. vel@ineos.ac.ru
authors.forename: Valeriya S
authors.initials: VS
authors.lastname: Velezheva
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Brennan
authors.forename: Vladimir Yu
authors.initials: VY
authors.lastname: Marshakov
authors.forename: Dmitrij V
authors.initials: DV
authors.lastname: Gusev
authors.forename: Inessa N
authors.initials: IN
authors.lastname: Lisichkina
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Peregudov
authors.forename: Larisa N
authors.initials: LN
authors.lastname: Tchernousova
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Smirnova
authors.forename: Sofia N
authors.initials: SN
authors.lastname: Andreevskaya
authors.forename: Alexei E
authors.initials: AE
authors.lastname: Medvedev
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000737:chemistry / Q000302:isolation & purification; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
chemical_list: D000995:Antitubercular Agents; D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D011724:Pyridazines; D008995:Monoamine Oxidase