Novel functions of o-cymen-5-ol nanoemulsion in reversing colistin resistance in multidrug-resistant Klebsiella pneumoniae infections.

Multidrug resistance (MDR) Klebsiella pneumoniae (K. pneumoniae) is a major emerging threat to human health, and leads to very high mortality rate. The effectiveness of colistin, the last resort against MDR Gram-negative bacteria, is significantly compromised due to the widespread presence of plasmid- or chromosome-mediated resistance genes. In this study, o-cymen-5-ol has been found to greatly restore colistin sensitivity in MDR K. pneumoniae. Importantly, this compound does not impact bacterial viability, induce resistance, or cause any noticeable cell toxicity. Various routes disclosed the potential mechanism of o-cymen-5-ol potentiating colistin activity against MDR K. pneumoniae. These include inhibiting the activity of plasmid-mediated mobile colistin resistance gene (mcr-1), accelerating lipopolysaccharide (LPS) - mediated membrane damage, and promoting the ATP-binding cassette (ABC) transporter pathway. To enhance the administration and bioavailability of o-cymen-5-ol, a nanoemulsion has been designed, which significantly improves the loading efficiency and solubility of o-cymen-5-ol, resulting in antimicrobial potentiation of colistin against K. pneumoniae infection. This study has revealed a new understanding of the o-cymen-5-ol nanoemulsion as a means to enhance the effectiveness of colistin against resistant factors. The finding also suggests that o-cymen-5-ol nanoemulsion could be a promising approach in the development of potential treatments for multidrug-resistant Gram-negative bacterial infections.

Pharmacophore and QSAR studies to design novel histone deacetylase 2 inhibitors.

One pharmacophore model and three quantitative structure-activity relationship models were developed on a series of benzimidazole and imidazole inhibitors of histone deacetylase 2. The goodness of hit score value of the best pharmacophore model was 0.756, which indicated that it is reliable to be used for virtual screening. The built pharmacophore model was used to search the NCI database. The hit compounds were subjected to molecular docking. The results showed that 25 compounds had high scores and strong interactions with histone deacetylase 2. In three-dimensional quantitative structure-activity relationship studies, good predictive models were obtained using comparative molecular field analysis, comparative molecular similarity indices analysis, and Topomer comparative molecular field analysis. Some putative active compounds were proposed based on compound no. 41. Twenty-six compounds had high scores and good interactions when they were docking into histone deacetylase 2.