Evaluation of antibacterial activity and reactive species generation of N-benzenesulfonyl derivatives of heterocycles

ALBESA I; MARTINEZ SR; MIANA G; MAZZIERI MR; BECERRA MC

CHEM. PHARM. BULL.

PHARMACEUTICAL SOC JAPAN

Lugar: Tokyo; Año: 2016 vol. 64 p. 135 - 141

0009-2363

Two N-benzenesulfonyl (BS) derivatives of 1,2,3,4-tetrahydroquinoline (THQ) were designed, prepared,and screened for antibacterial activity. This approach was based on combining the two privileged structures,BS and THQ, which are known to be active. The objective of this study was to evaluate the antibacterial activityof BS-THQ and its analogue 4-NH2BS-THQ, and to investigate the roles of reactive oxygen species andreactive nitrogen species in their lethality. Both showed bactericidal activity against Staphylococcus aureus ATCC 29213 and methicillin-resistant S. aureus (MRSA) ATCC 43300, with transmission electron microscopy revealing a disturbed membrane architecture. Furthermore, an increase of reactive oxygen species (ROS) in strains treated with BS-THQ with respect to the control was detected when fluorescent microscopy and spectrophotometric techniques were used. The analogue 4-NH2BS-THQ demonstrated a broader spectrum of activity than BS-THQ, with a minimum inhibitory concentration of 100 μg/mL against reference strains of S. aureus, Escherichia coli and Pseudomonas aeruginosa. The assayed compounds represent promising structures for the development of new synthetic classes of antimicrobials.