Synthesis and Evaluation of Novel Substituted N-Aryl 1,4-Dihydropyridines as Antituberculostatic Agents

Abstract

Background: Tuberculosis has been the main cause of mortality of infectious diseases worldwide, with strongly limited therapeutic options. With increasing resistance and missing suitable drugs in those cases, there is a strong need for novel antituberculostatic drugs. We developed novel N-aryl 1,4-dihydropyridines with various substitution patterns to evaluate them as antituberculostatic agents.

Methods: 1,4-Dihydropyridine derivatives were synthesized and purified by column chromatography or recrystallization. The mycobacterial growth inhibition was determined in a fluorescent mycobacterial growth assay.

Results: The compounds were prepared in a simple one-pot reaction under acidic conditions with structurally varied components. The substituent effects on the determined mycobacterial growth inhibitory properties are discussed.

Conclusion: Lipophilic diester substituted derivatives show promising activities that were additionally affected by the aromatic substituent functions. Thus, we identified compounds with activities almost reaching that of the used antimycobacterial drug as control.

Keywords: Drug research; antimycobacterial drug; lipophilc diester; small molecule inhibitor; structure-activity relationships; tuberculosis..