Siderophores are small molecules produced by bacteria under iron-scarcity conditions faced by bacteria inside host. Sideophores bind iron with high affinity (Kd < 10-25 M) and are required for iron transport into the bacterial cell. Small molecules interfering with siderophore functioning can be promising anti-mycobacterial agents. Several molecules with hydrazone as a structural feature are known to have metal chelating property. This prompted us to investigate the metal chelating ability of 2-hydrazino-pyrimidin-4(3H)-one derivatives. In this light, a library of 22 novel molecules with 2- hydrazino-pyrimidin-4(3H)-one moiety was synthesized and the compounds were evaluated against M. tuberculosis under iron-limiting and iron-rich conditions. Interestingly, several molecules showed promising (MIC: < 10 μM) selective activity under iron scarcity conditions. Furthermore, compounds were found to be nontoxic at lower concentration in VERO cell lines using MTT assay. Taken together, we have discovered novel 2-hydrazino-pyrimidin-4(3H)-one molecules active against M. tuberculosis which can be developed as potent antimycobacterial agents.
in Wiley InterScience (www.interscience.wiley.com).Novel substituted 2-hydrazino-pyrimidin-4(3H)-one derivatives were synthesized and examined for their antifolate activity against DHFR from Pneumocystis carinii (pc), Toxoplasma gondii (tg), Mycobacterium avium (ma), and rat liver (rl). A novel, simple, and feasible methodology was developed for the synthesis of the titled compounds. Amongst these, compound 8 6-phenyl-2-(2-(1-(thiophen-2-yl) ethylidene)hydrazinyl) pyrimidin-4(3H)-one exhibited 17.74 lM activity against pcDHFR.
Novel Molecular Hybrids of Cinnamic Acids and Guanylhydrazones as Potential Antitubercular Agents. -Design, synthesis and evaluation of the title compounds (III) (20 examples) for their antitubercular activity are described. Based on empirical structure-activity relationship data, it was observed that both steric and electronic parameters play a major role in the activity of this series. Compound (IIIf), the most potent sample, exhibits a good safety profile with selectivity index > 50. Thus, this compound can act as a potential lead for further antitubercular studies.
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