Factor analysis of microbiological activity data and structural parameters of antibacterial quinolones

Abstract

Factor analysis (FA) was performed on quinolone derivatives with antibacterial activity to model relationships between molecular descriptors and microbiological activities determined on five bacterial cell lines (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pneumoniae). Molecular modeling studies were performed with the use of HyperChem software and MM+ molecular mechanics with the semi-empirical AM1 method. Factor analysis led to the extraction of two main factors, with the share of factor 1 amounting to about 76% and factor 2 to about 24% for all the parameters used in the statistical analysis. Moreover, FA results indicated that energy of orbitals lowest unoccupied molecular orbital, energy of ionization, electron affinity, electronegativity, maximum electron density, refraction and polarizability appeared to be descriptors important for the antibacterial activity of quinolones.

Anodic oxidation of selenadiazoloquinolones in alkaline media

“…However, the antibiotic resistance developed among pathogenic bacteria requires permanent research into alternative preparations possessing antimicrobial effects 3, 5. Numerous novel quinolone derivatives have been synthesized, and a great deal of attention has been focused on the investigation of their physicochemical properties and biological activities 7–13. The presence of selenium in molecules can provide new properties, and some of the synthesized selenaheterocyclic compounds have demonstrated positive biological impact 14–16.…”

Recent Strategies in Design of Antitumor and Antibacterial Fluoroquinolones

“…Quinolones have been categorized into four generations, based on their spectrum of activity and pharmacokinetic features [21][22][23]. The first generation of quinolones displayed antibacterial activities only toward the species of Gram-negative bacteria, but they have restricted uses due to short duration of action and rapid renal clearance [24]. Also, they are suffering from minimum serum level, narrow spectrum of activity, and rapid development of bacterial resistance.…”

Recent updates of fluoroquinolones as antibacterial agents

“…Fluoroquinolones are classified on the basis of their spectrum of activity and their pharmacokinetic profile . First generation quinolones including nalidixic acid 1 , oxolinic acid 2 , pipemidic acid 3 , and rosoxacin 4 showed activity against Gram‐negative bacteria, but they have limited uses due to short serum half‐lives as result of rapid renal elimination . Therefore, they are only used in treatment of urinary tract infections caused by Gram‐negative bacteria, and rarely used today …”

“…So, they exhibited wider activity against Gram‐negative bacteria, including Pseudomonas aeruginosa , good activity against Gram‐positive bacteria and showing longer serum half‐lives. They are used in treatment of tissue‐based diseases such as complicated bladder infections, pyelonephritis, sexually transmitted diseases, specific types of pneumonia, skin infections, and urinary tract infections …”