Correlation study of antibacterial activity and spectrum of Penicillins through a structure-activity relationship analysis

Abstract

Penicillins are a group of antibiotics of the beta-lactam group, widely used worldwide as first-choice drugs in the treatment of infections caused by sensitive bacteria. Their use is based on an empirical measure of their activity through antibiograms. In this work we have carried out a structure-activity relationship analysis to elucidate the molecular and physicochemical bases that determine the antibacterial activity and the orientation of the antibacterial spectrum of penicillins, employing a set of bacteria that cause common infections. It was found that the antibacterial activity increases as penicillin size increases for both, Gram-negative and Gram-positive bacteria. In the same way, liposolubility affects the activity; water soluble penicillins have greater activity on Gram-negative bacteria, while in some cases liposoluble penicillins present higher activity against Gram-positive bacteria. In addition, it is proposed that electronic properties of the substituent of the penicillin core determine its antibacterial spectrum. The electron donating substituents make the penicillin active against Gram-positive bacteria, while the electron withdrawing substituents gear the activity towards Gram-negative bacteria. In addition, the alpha-carbon (Cα) of the carboxamide side chain is also essential for the activity against Gram-negative bacteria; penicillins that lack it, have higher activity against Gram-positive bacteria.