title: Design, Synthesis and Evaluation of Antitubercular Activity of Novel Dihydropyridine Containing Imidazolyl Substituent.
abstract: Recent studies have indicated that 1, 4-dihydropyridine-3, 5-dicarboxamide derivatives show significant anti-tubercular activity. In this research, new derivatives of 1, 4-dihydropyridine were designed and synthesized using Hantzsch condensation in which dicyclohexyl and different dicyclohexylcarbamoyl were substituted at C-3 and C-5 positions of the DHP ring. In addition, 4 (5)-chloro-2-methyl-5 (4)-imidazolyl moiety was substituted at C-4 position of DHP. The structure of synthetized compounds were characterized by TLC, IR, elemental analysis and proton NMR. Based on the in vitro screening data, all of the designed and synthetized compounds (3a-3g) showed a good ability to inhibit the mycobacterium tuberculosis growth in terms of MIC. Aromatic carboxamide containing compounds were more potent than cyclohexyl derivative and the most potent compound was 3a (4-nitrophenyl derivative). The experimental data are in agreement with our computational predictions in terms of partial atomic charge of carbonyl moieties at the C-3 and C-5 positions of DHP ring and partition coefficient of the molecules.
authors.affiliation: Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Iman
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (IAUPS).
authors.forename: Asghar
authors.initials: A
authors.lastname: Davood
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (IAUPS).
authors.forename: Golnoush
authors.initials: G
authors.lastname: Dehqani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran (IAUPS).
authors.forename: Mahboubeh
authors.initials: M
authors.lastname: Lotfinia
authors.affiliation: Department of Bioinformatics and Drug design, Institute Pasteur, Tehran, Iran.
authors.forename: Soroush
authors.initials: S
authors.lastname: Sardari
authors.affiliation: Department of Bioinformatics and Drug design, Institute Pasteur, Tehran, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Azerang
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
keywords: Dihydropyridine; Imidazole; Mycobacterium; Synthesis; Tuberculosis