Title:GlmU Inhibitors as Promising Antibacterial Agents: A Review
Volume: 23
Issue: 3
Author(s): Nagarjuna Palathoti and Mohammed Afzal Azam*
Affiliation:
- Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research,
Ooty, Nilgiris, Tamil Nadu, India
Keywords:
Haemophilus influenzae, acetyltransferase, uridyltransferase, GlmU inhibitors, quinazolines, 2-phenylbenzofuran, HTVS.
Abstract: Bacterial infections are a major cause of mortality and morbidity in humans throughout
the world. Infections due to resistant bacterial strains such as methicillin-resistant Staphyloccocusaureus
vancomycin, resistant Enterococci, Klebsiella pneumoniae, Staphylococcus aureus,
and Mycobacterium are alarming. Hence the development of new antibacterial agents, which act
via a novel mechanism of action, became a priority in antibacterial research. One such approach
to overcome bacterial resistance is to target novel protein and develop antibacterial agents that act
via different mechanisms of action. Bacterial GlmU is one such bifunctional enzyme that catalyzes
the two consecutive reactions during the biosynthesis of uridine 5′-diphospho-Nacetylglucosamine,
an essential precursor for the biosynthesis of bacterial cell wall peptidoglycan.
This enzyme comprises two distinct active sites; acetyltransferase and uridyltransferase and both
these active sites act independently during catalytic reactions. GlmU is considered an attractive
target for the design and development of newer antibacterial agents due to its important role in
bacterial cell wall synthesis and the absence of comparable enzymes in humans. Availability of
three dimensions X-crystallographic structures of GlmU and their known catalytic mechanism
from different bacterial strains have instigated research efforts for the development of novel antibacterial
agents. Several GlmU inhibitors belonging to different chemical classes like 2-
phenylbenzofuran derivative, quinazolines, aminoquinazolines, sulfonamides, arylsulfonamide,
D-glucopyranoside 6-phosphates, terreic acid, iodoacetamide, N-ethyl maleimide, and Nethylmaleimide
etc., have been reported in the literature. In the present review, we present an update
on GlmU inhibitors and their associated antibacterial activities. This review may be useful
for the design and development of novel GlmU inhibitors with potent antibacterial activity.
