Title:Synthesis and Evaluation of Novel Substituted N-Aryl 1,4-Dihydropyridines as Antituberculostatic Agents
Volume: 20
Issue: 1
Author(s): Lisa Seitz, Norbert Reiling, Christopher Vorreiter, Wolfgang Sippl, Sonja Kessler and Andreas Hilgeroth*
Affiliation:
- Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck Str. 4, 06120 Halle,
Germany
Keywords:
Drug research, small molecule inhibitor, structure-activity relationships, antimycobacterial drug, lipophilc diester, tuberculosis.
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.