Moxalactam Disodium

Animal species, i.e. rats, are used to evaluate a drugs biol. activity and pharmacokinetics, such as clearance.This study aims to develop a predictive method to evaluate the relationship between the clearance of drugs in rats and humans.Adataset of 395 drugs composed of human and rat clearance data was applied in this study.The drugs, according to the clearance differences, were divided into two groups on the basis of the correlation between humans and rats.Structural parameters were used to develop a model to estimate the class of each drug by binary logistic regression.The results showed that the developed models are a useful way to show which drug have an acceptable correlation between human and rat clearance by using structural features.They can be used to determine the group of drugs with an accuracy of 74%.According to the validation results, the developed method has an acceptable accuracy for checking the relationship between the clearance of drugs in humans and rats.This modeling can be used to exclude the drugs from experiments in rats which reveal a considerable difference between the clearance of humans and that of rats.

Antimicrobial resistance poses a significant challenge to public health, especially in developing countries, due to a substantial rise in bacterial resistance. This situation has become so concerning that we are now at risk of losing the effectiveness of antibiotics altogether. Recent research has firmly established that bacteria engage in a process called quorum sensing (QS). QS regulates various functions, including nutrient scavenging, immune response suppression, increased virulence, biofilm formation and mobility. Pseudomonas aeruginosa, an opportunistic bacterial pathogen, plays a significant role in various medical conditions such as chronic wounds, corneal infections, burn wounds and cystic fibrosis. While antibiotics are effective in killing bacteria, only a few antibiotics, particularly those from the β-lactam group, have been studied for their impact on the quorum sensing of P. aeruginosa. Given the lack of concentrated efforts in this area, we have investigated the role of β-lactam antibiotics on various potential targets of P. aeruginosa. Based on their toxicological profiles and the average binding energy obtained through molecular docking, azlocillin and moxalactam have emerged as lead antibiotics. The binding energy for the docking of azlocillin and moxalactam with LasA was determined to be -8.2 and -8.6 kcal/mol, respectively. Molecular simulation analysis has confirmed the stable interaction of both these ligands with all three target proteins (LasI, LasA and PqsR) under physiological conditions. The results of this research underscore the effectiveness of azlocillin and moxalactam. These two antibiotics may be repurposed to target the quorum sensing of P. aeruginosa.Communicated by Ramaswamy H. Sarma.