IN-SILICO STRUCTURE-ACTIVITY RELATIONSHIP AND MOLECULAR DOCKING STUDY OF LEVOFLOXACIN AND ITS MONO SUBSTITUTED ANALOGUES AGAINST THE ESCHERICHIA COLI AMINOGLYCOSIDE PHOSPHOTRANSFERASE

Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotics. Aminoglycoside phosphotransferases provide an important means for high-level resistance to aminoglycoside antibiotics. Levofloxacin is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. Extensive structure activity relationship study was carried out with levofloxacin and its monosubstituted analogues which were designed by substituting the levofloxacin F group for C=O, CH3, NH2 and OH functional groups using the Marvin Sketch software. This was followed by a molecular docking study to target the experimental ligands against the E. coli aminoglycoside phosphotransferase active site. The result of the molecular docking study showed that the OH analogue of levofloxacin might be the better antibiotics to combat the resistance exhibited by the E. coli against aminoglycoside antibiotics