Name: Sunit Kumar Jana
Diploma / M.Sc degree: IIT Bombay, India
(May 2010)

PhD Project: Design and Synthesis of Potent LpxC Inhibitors against Gram Negative Bacteria

Abstract of Research Project

The current medical cure of gram-negative bacterial infections involves antibiotics, including penicillins (ticarcillin), and carbapenems (imipenem-cialiastin and meropenem) and aminoglycosides (tobramycin). However with the emergence of multidrug resistant bacteria, there is an urgent need for the identification of antibiotics with novel mechanisms of action to complement existing drugs that inhibit protein, nucleic acid or cell wall synthesis. The deacetylation of uridyldiphospho-3-O-((R)-hydroxymyristoyl)-N-acetylglucosamine, catalysed by a Zinc dependent deactylase known as LpxC, is the second committed step of the biosynthesis of Lipid A, the hydrophobic anchor component of lipopolysaccharide (LPS). LPS constitutes the outermost monolayer of various gram-negative bacteria. Because LPS is essential for bacterial growth and viability, the inhibition of LpxC represents an appealing therapeutic strategy for the treatment of gram-negative bacterial infection. CHIR- 090, the most potent LpxC inhibitor currently available, inhibits a diverse range of LpxC orthologous from various bacterial species like E. coli and P. aeruginosa. The development of conformationally constrained CHIR-090 derivatives as LpxC inhibitors is the major focus of our current research.



Publications

S. K. Jana, M. Löppenberg, C. G. Daniliuc, J. Jose, R. Holl
Development of novel LpxC inhibitors: chiral-pool synthesis of C-triazolyl glycosides
Tetrahedron 69 (2013), 9434-9442.


Sunit Kumar Jana
eMail: Sunit Kumar Jana