Evaluation of potential bacterial protease inhibitor properties of selected hydroxyquinoline derivatives: an in silico docking and molecular dynamics simulation approach.

Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from -2.17 to -8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies.Communicated by Ramaswamy H. Sarma.

Oral Erythromycin Improves the Quality of Endoscopy in Upper Gastrointestinal Bleeding Patients.

Background Upper gastrointestinal bleeding is a life-threatening emergency. Endoscopy is the therapeutic and diagnostic procedure of choice after initial stabilization of the patient. But the presence of retained blood, blood products, and other residual material in the stomach is a big challenge for endoscopists during urgent endoscopy after acute upper gastrointestinal bleeding. Intravenous erythromycin before endoscopy improves the visualization of gastric and duodenal mucosa in these patients. Use of oral erythromycin is more easy and convenient, so the objective of our study was to assess the effects of oral erythromycin on quality of endoscopy in upper gastrointestinal bleeding patients. Methods This interventional study was conducted at the Department of Medicine, POF Hospital Wah Cantt, Pakistan from January 2019 to December 2019. Patients with clinical evidence of acute upper gastrointestinal bleeding within 12 hours were inducted consecutively. Patients were randomly assigned to erythromycin (500 mg) suspension or placebo, orally three hours before endoscopy. One endoscopist performed all the procedures with the same double-channel video endoscope. The primary endpoint was endoscopic quality. The secondary endpoints were the need for second-look endoscopy within 48 hours, endoscopy related complications, therapeutic procedure performed or not during endoscopy, number of blood transfusions, and length of hospital stay. Results A total of 60 patients were included in the study; 30 received erythromycin and 30 received placebo. Out of these, 60% were male and 40% were female. The mean age was 53.68 ± 16.64. Quality of endoscopy was much better in the erythromycin group (83.3%) as compared to placebo (40%). Erythromycin did not shorten the endoscopic duration (15.53 vs. 14.33 minutes in the placebo group; p=0.216) and length of hospital stay (5.23 in erythromycin vs. 5.40 days in placebo group; p=0.807). Statistically no significant association was found between use of erythromycin and establishment of cause of bleed, need for second-look endoscopy, number of blood transfusions and number of endoscopic therapeutic procedures. Conclusion Erythromycin oral suspension before endoscopy in patients with acute upper gastrointestinal bleeding produced good quality of endoscopy in our study. It improved the visualization of gastric and duodenal mucosa significantly. However, it did not shorten the duration of endoscopy or hospital stay. There was no significant difference in number of second-look endoscopies and blood transfusions as well.