Potentially active aspirin derivative to release nitric oxide: In-vitro, in-vivo and in-silico approaches.

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of -8.35, -9.67 and -8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski's rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

An Overview of Diabetic Foot Ulcers and Associated Problems with Special Emphasis on Treatments with Antimicrobials.

One of the most significant challenges of diabetes health care is diabetic foot ulcers (DFU). DFUs are more challenging to cure, and this is particularly true for people who already have a compromised immune system. Pathogenic bacteria and fungi are becoming more resistant to antibiotics, so they may be unable to fight microbial infections at the wound site with the antibiotics we have now. This article discusses the dressings, topical antibacterial treatment, medications and debridement techniques used for DFU and provides a deep discussion of DFU and its associated problems. English-language publications on DFU were gathered from many different databases, such as Scopus, Web of Science, Science Direct, Springer Nature, and Google Scholar. For the treatment of DFU, a multidisciplinary approach involving the use of diagnostic equipment, skills, and experience is required. Preventing amputations starts with patient education and the implementation of new categorization systems. The microbiota involved in DFU can be better understood using novel diagnostic techniques, such as the 16S-ribosomal DNA sequence in bacteria. This could be achieved by using new biological and molecular treatments that have been shown to help prevent infections, to control local inflammation, and to improve the healing process.