DECIPHERING THE MODE OF ACTION AND PHARMACOKINETICS POTENTIAL OF NOVEL ANTIBACTERIAL AGENTS

Abstract

Infectious diseases remain an arduous task to manage and mitigate throughout the ages. Drug discovery platform has revolutionized the era of modern medicine and revamped our modern way of life very healthy and possible. Bacterial infections are the major cause of death around the globe among all the infectious diseases today. The rise of multidrug-resistant bacteria (MDR) is a challenging clinical and biological phenomenon since the discovery of Penicillin as a miracle drug to cure bacterial infections. Almost all the bacterial pathogens have acquired a high level of multidrug-resistance (MDR) with soaring morbidity and mortality due to chronic illness, and thus they are known as “Superbugs." Although the existence and development of resistance mechanisms is a natural selective pressure for survival and fitness in the changing environment, the injudicious use of antimicrobial drugs for human consumption and in livestock farming, poor sanitary conditions, mismanagement of food processing and handling, and poor preventive measures for infection monitoring and control come up with the surfacing and spread of multidrug-resistance into the community. The various emerging resistance mechanisms have decreased the therapeutic potency and efficiency of currently available antibiotics in treating common bacterial diseases, ultimately failing to standardize empirical treatment and the higher burden on health care. Antibacterial resistance develops at an increasing rate among Gram-positive and Gram-negative infectious agents against all the classes of antibiotics available in the clinics. Still, the more compelling threat is the emergence of multidrug-resistant Gram-negative bacterial pathogens against the last resort of antibiotics in use. The more potent antibiotics were discovered after the introduction of Penicillin in 1928 using different strategies like drug molecule analogues designing, understanding drug-target interaction for further modification of existing drug molecules, and developing a new scaffold. The problematic scenario is that the innovation pace has reduced in the last five decades. Only a few new classes of antibiotics or analogues of the existing antibiotics have been introduced against the Gram-negative pathogens. Therefore, improving the success of modern antibacterial drug discovery and the development of a new antibacterial class is urgently needed with a unique structural scaffold, potential therapeutic window, and new molecular targets.