Synthesis and biological evaluation of some new 1,4-dihydropyridines containing different ester substitute and diethyl carbamoyl group as anti-tubercular agents.
Tuberculosis is a leading infectious cause of death worldwide. Because of the concern of the resistance to most of the commonly used drugs displayed by the considered mycobacteria, most efforts have been done to introduce new anti-tubercular agents. Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with lipophilic groups have significant anti-tubercular activity. In this study, we synthesized new derivatives of 1,4-dihydropyridines in which different alkyl and aryl esters and diethyl carbamoyl are substituted in C-3 and C-5 of the DHP ring. In addition nitroimidazole ring is substitutes at C-4 position. These asymmetric analogues were synthesized by a modified Hantzsh reaction using procedure reported by Meyer. The in vitro anti-tubercular activity of compounds against Mycobacterium tuberculosis was evaluated. The results indicate that the compounds containing aromatic esters are more potent than alkyl ones. The most potent aromatic compound (R=3-phenylpropyl) exhibits comparable anti-tubercular activity (MIC=1 micromol/ml) with reference compound isoniazide (INH) (MIC=1 micromol/ml). Conformational analysis, SAR studies of these compounds showed that increasing in lipophilicity and rotable bonds of these compounds resulted in increasing anti-tubercular activity.
Khoshneviszadeh
Mehdi
M
Medicinal and Natural Products Chemistry Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran.
Edraki
Najmeh
N
Javidnia
Katayoun
K
Alborzi
Abdolvahab
A
Pourabbas
Bahman
B
Mardaneh
Jalal
J
Miri
Ramin
R
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D004095:Dihydropyridines