ABSTRACT
Caffeine (CA) is a methylxanthine alkaloid widely used in anti-inflammatory drug associations due to itsvasoconstricting properties. Although CA is acknowledged to interact with a plethora of macromolecules inhuman organism, there was to the best of our knowledge, no survey regarding its possible interactions withcommon inflammation-related targets. Henceforth, this work was concerned in the investigation of CA possibleinteractions with cyclooxygenases-1 and -2 (COX-1 and COX-2), as well as prostaglandin H2 synthase-1and leukotriene A4 hydrolase through in silico approaches. CA molecule was studied as a ligand whereas theligand-macromolecules docking models were created through AutoDock Vina tools. Results showcased that,although the thermodynamic features of the best scoring models did not render enough information to affirmstable interaction between CA and the analyzed macromolecules, more studies are needed to shed light on thepossible role of methylxanthines towards inflammation targets.
ABSTRACT
Bacteria resistance to antibacterial antibiotics is made possible by theproduction of beta-lactamase. Beta-lactamase enzyme confers resistance by breakingopen the Beta-lactam structure of antibiotics, thereby deactivating their antibacterialproperties. As a result of this, attention shifted into identifying potential lead inhibitorof beta-lactamase, with ability to reduce resistance encountered in bacteria antibiotics.The computational approach was employed in the generation of QSAR model usingAutomated QSAR, and in the docking of ligands from Chromolaena odorata with Betalactamase. The best model obtained was KPLS_Dendritic_43 (R2 = 0.8564 andQ2=0.7819), and was used in predicting the bioactivity of the lead compounds. Dockingstudy revealed that the ligands bind with a higher binding score than co-crystallizedligand and other standard drug employed in this study. Tianshic acid and chromomoraterecorded binding energy of -9.305 and -7.989 respectively. The drug-like properties ofthe ligands were evaluated using the Lipinski rule of Five, which revealed that C. odorataligands do not only inhibit the activity of beta-lactamase, but the ligands are also druglike. Therefore, further studies are needed to adequately justify the mechanism of actionof these ligands as a beta-lactamase inhibitor.
ABSTRACT
Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (−38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of 0.286 μg/L against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.