Abstract
Though clinicians once possessed a robust arsenal of antibiotics, many of these valuable therapeutic agents have fallen prey to the expanded resistance of pathogenic bacteria. Phenylthiazoles were reported previously as a new scaffold that possesses antibacterial activity against an array of clinically-relevant strains of multidrug-resistant staphylococci. Close inspection of the structure-activity-relationships (SAR) of phenylthiazoles revealed important structural features necessary for their antibacterial activity: a nitrogenous head and a lipophilic tail. Incorporating the nitrogenous part within an oxadiazole ring resulted in analogues with a prolonged half-life, while the biphenyl tail revealed the most potent analogue. In the present work, advantageous moieties have been combined together to generate new hybrid scaffolds of phenylpyridine with the objective of promoting new moieties enhancing both antimicrobial resistance activity and drug-like properties. Among the tested oxadiazolylbiphenylpyridines, derivatives 14 and 23 were identified as the most potent analogues with MIC values as low as 8 mg/mL on MRSA-US300 and other studied species.
Highlights
The search for new antibiotics has improved human health status by suppressing life-threatening infections
The emergence and spread of bacterial resistance represent a severe global problem; the number of life-threatening infectious diseases caused by multidrug-resistant bacteria has reached an alarming level in many countries around the world. (Parmar et al, 2003) there is both substantial need and market for more effective treatments of bacterial and fungal infections
One way to overcome the rapid development of drug resistance to the currently used antimicrobials is to develop new agents, preferably with chemical characteristics that vastly differ from those of existing ones.(Desai et al, 2014) Phenylthiazoles were reported as a new scaffold acting as dual UppP and UppS inhibitors with wide antimicrobial activity against multidrug-resistant gram-positive strains including MRSA, VRSA and VRE(Haroon Mohammad et al, 2014a) with selective advantage over vancomycin.(H
Summary
The search for new antibiotics has improved human health status by suppressing life-threatening infections. Novel solutions to the issue are necessary since the currently used antimicrobial agents are no longer sufficient to prevent certain infections from propagating and spreading due to resistance development. One way to overcome the rapid development of drug resistance to the currently used antimicrobials is to develop new agents, preferably with chemical characteristics that vastly differ from those of existing ones.(Desai et al, 2014) Phenylthiazoles were reported as a new scaffold acting as dual UppP and UppS inhibitors with wide antimicrobial activity against multidrug-resistant gram-positive strains including MRSA, VRSA and VRE(Haroon Mohammad et al, 2014a) with. Pyridines showed potent antimicrobial activity against wide range of microorganisms.(Prakash et al, 2011) we wish to report here the synthesis of a new series of oxadiazolylbiphenylpyridine scaffold possessing anti-microbial activities. All spectral measurements have been performed at the Micro analytical Center, Zagazig University, Egypt
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