Design, Synthesis and Evaluation of Antitubercular Activity of Novel Dihydropyridine Containing Imidazolyl Substituent

Iman, Maryam; Davood, Asghar; Dehqani, Golnoush; Lotfinia, Mahboubeh; Sardari, Soroush; Azerang, Parisa; Amini, Mohsen

doi:10.22037/ijpr.2015.1744

Design, Synthesis and Evaluation of Antitubercular Activity of Novel Dihydropyridine Containing Imidazolyl Substituent

Document Type : Research article

Authors

¹ Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

² Department of Medicinal Chemistry, Pharmaceutical Sciences branch, Islamic Azad University, Tehran, Iran

³ Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran.

⁴ Department of Bioinformatics and Drug design, Institute Pasteur, Tehran, Iran

⁵ Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

10.22037/ijpr.2015.1744

Abstract

Recent studies have indicated that 1, 4-dihydropyridine-3, 5-dicarboxamidederivativesshow 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 dicyclohexylcarbamoylwere substituted at C-3 and C-5 positions of the DHP ring.In addition, 4 (5)-chloro-2-methyl-5 (4)-imidazolylmoiety 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 agood ability to inhibit the mycobacterium tuberculosis growth in terms of MIC. Aromatic carboxamide containing compounds were more potent than cyclohexylderivative 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.

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