Abstract
A series of novel N-benzylidenesulfonohydrazide compounds were designed and synthesized as inhibitors of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) and UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase (MurD) from E. coli, involved in the biosynthesis of bacterial cell-walls. Some compounds possessed inhibitory activity against both enzymes with IC50 values as low as 30 μM. In addition, a new, one-pot synthesis of amidobenzaldehydes is reported.
Highlights
The increasing emergence of pathogenic bacterial strains with high resistance to antibacterial agents constitutes a serious public health threat
The compounds with general structure 5a-i were synthesized starting from hydroxybenzaldehydes 3a or 3b, which were treated with the corresponding benzyl halides to yield compounds 4 in high yield (75-90%), except for 4b (13%)
Sulfonate derivatives 7a-c were synthesized in a similar manner, starting from the hydroxybenzaldehyde 3b, which was treated with the appropriate phenylsulfonyl chlorides to give 6ac in 57-68% yield, and coupled with naphthalene-2-sulfonohydrazide hydrochloride to give the targets 7a-c in 46-80% yield
Summary
The increasing emergence of pathogenic bacterial strains with high resistance to antibacterial agents constitutes a serious public health threat. We have described the synthesis and structure-activity relationship of a series of novel N’-benzylidenesulfonohydrazides as inhibitors of MurC and MurD and as potential lead compounds for the development of new antibacterial drugs.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
