Novel 2-hydrazino-pyrimidin-4(3H)-one derivatives with pseudofunctional- similarity to siderophores as potential antimycobacterial agents.
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.
Institute of Chemical Technology, Nathalal Parikh Marg, Matunga, Mumbai-400019, India.
Ranjeet
R
Bairwa
Nilesh R
NR
Tawari
Amruta
A
Alate
Swapnil
S
Anam
Mariam S
MS
Degani
Muktikant
M
Ray
Ramakrishna M G
RM
Rajan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017262:Siderophores / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
D000900:Anti-Bacterial Agents; D006834:Hydrazines; D007502:Iron Chelating Agents; D011744:Pyrimidinones; D017262:Siderophores; D054852:Small Molecule Libraries