Medicinal Chemistry of Inhibitors Targeting Resistant Bacteria

Abstract

ABSTRACT: The discovery of antibiotics was a revolutionary feat that provided countless health bene-fits. The identification of penicillin by Alexander Fleming initiated the era of antibiotics, represent-ed by constant discoveries that enabled effective treatments for the different classes of diseases caused by bacteria. However, the indiscriminate use of these drugs allowed the emergence of re-sistance mechanisms of these microorganisms against the available drugs. In addition, the constant discoveries in the 20th century generated a shortage of new molecules, worrying health agencies and professionals about the appearance of multidrug-resistant strains against available drugs. In this context, the advances of recent years in molecular biology and microbiology have allowed new per-spectives in drug design and development, using the findings related to the mechanisms of bacterial resistance to generate new drugs that are not affected by such mechanisms and supply new mole-cules to be used to treat resistant bacterial infections. Besides, a promising strategy against bacterial resistance is the combination of drugs through adjuvants, providing new expectations in designing new antibiotics and new antimicrobial therapies. Thus, this manuscript will address the main mech-anisms of bacterial resistance under the understanding of medicinal chemistry, showing the main active compounds against efflux mechanisms, and also the application of the use of drug delivery systems, and finally, the main potential natural products as adjuvants or with promising activity against resistant strains.