Alkoxyphenylthiazoles with broad-spectrum activity against multi-drug resistant gram-positive pathogens.

Abstract

Abstract t

With the continued rise of antibiotic resistance and reduced susceptibility to almost all front-line antibiotics, multidrug-resistant Gram-positive bacterial infections represent an incessant threat to healthcare providers. Antibiotic resistance kills an estimated 700,000 people each year worldwide, and some experts predict that number to reach 10 million by 2050 if efforts are not made to curtail resistance or develop new antibiotics. Although the development of second- and third antibacterial generations from the existing classes of antibiotics has improved the overall activity, bacterial resistance to these known drugs is on an exponential rise. Previously, phenylthiazoles have been identified as a new scaffold with a notable efficacy against highly mutlidrug-resistant Gram-positive pathogens by using HTS on a wide variety of methicillin and vancomycin-resistant Staphylococcus aureus strains. Unfortunately, the promising activity of this novel class of antibiotics was hampered by their short half-life due to rapid hepatic metabolism. The lead compound 1a, as a representative example, was cleared by liver microsomes at a rate of 80.3 μL/min-mg.