2010
DOI: 10.1021/jm100568q
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Inhibition of Mycobacterial Replication by Pyrimidines Possessing Various C-5 Functionalities and Related 2′-Deoxynucleoside Analogues Using in Vitro and in Vivo Models

Abstract: Tuberculosis (TB) has become an increasing problem since the emergence of human immunodeficiency virus and increasing appearance of drug-resistant strains. There is an urgent need to advance our knowledge and discover a new class of agents that are distinct than current therapies. Antimycobacterial activities of several 5-alkyl, 5-alkynyl, furanopyrimidines and related 2'-deoxynucleosides were investigated against Mycobacterium tuberculosis. Compounds with 5-arylalkynyl substituents (23-26, 33, 35) displayed p… Show more

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Cited by 33 publications
(25 citation statements)
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“…At a dose of 50 mg/kg for 5 weeks, statistically significant reduction in mycobacterial load was observed in lungs, livers and spleens of the treated mice. This is the first evidence of antimycobacterial potential of 5-substituted pyrimidine nucleosides in an animal model as a potential new class of antituberculosis agents [58]. …”
Section: Drug Discovery Programmentioning
confidence: 99%
“…At a dose of 50 mg/kg for 5 weeks, statistically significant reduction in mycobacterial load was observed in lungs, livers and spleens of the treated mice. This is the first evidence of antimycobacterial potential of 5-substituted pyrimidine nucleosides in an animal model as a potential new class of antituberculosis agents [58]. …”
Section: Drug Discovery Programmentioning
confidence: 99%
“…In 2010 the first antimycobacterial in vivo data in a mouse model infected with H37Ra M.tb strain were published [126]. After synthesis and antimycobacterial in vitro evaluation of a novel series of 5-alkyl and 5-alkyl(or aryl)alkynyl pyrimidines, 5-(2-pyridylethynyl)-uracil (74) was selected as a potent candidate for further investigations ( Figure 14A) [126].…”
Section: Nucleoside Analogs With Unclear Targetmentioning
confidence: 99%
“…After synthesis and antimycobacterial in vitro evaluation of a novel series of 5-alkyl and 5-alkyl(or aryl)alkynyl pyrimidines, 5-(2-pyridylethynyl)-uracil (74) was selected as a potent candidate for further investigations ( Figure 14A) [126]. The promising in vitro activity of this compound (MIC 50 = 1-5 μg/ml on M. bovis, MIC 50 = 5 μg/ml on M.tb] prompted to in vivo evaluation of its efficacy in female BALB/c mice infected with H37Ra at a dose of 50 mg/kg, formulated in 10% DMSO-saline, by the intraperitoneal route.…”
Section: Nucleoside Analogs With Unclear Targetmentioning
confidence: 99%
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“…Nucleoside analogues are also extensively studied as therapeutic agents against the proliferation of cancer cells, against virus replication, and, recently, also against bacterial infections (24). Among them, the 2=-deoxy-4=-thiopyrimidine nucleosides have been reported to be inhibitors of some herpesviruses, and they are listed in Table 1 (25,26).…”
mentioning
confidence: 99%