Integrating structure-guided and fragment-based inhibitor design to combat bedaquiline resistant : a molecular dynamics study.

The first FDA approved, MDR-TB inhibitory drug bedaquiline (BDQ), entraps the c-ring of the proton-translocating F region of enzyme ATP synthase of , thus obstructing successive ATP production. Present-day BDQ-resistance has been associated with cardiotoxicity and mutation(s) in the atpE gene encoding the c subunit of ATP synthase (ATPc) generating five distinct ATPc mutants: Ala63→Pro, Ile66→Met, Asp28→Gly, Asp28→Val and Glu61→Asp. We created three discrete libraries, first by repurposing bedaquiline via scaffold hopping approach, second one having natural plant compounds and the third being experimentally derived analogues of BDQ to identify one drug candidate that can inhibit ATPc activity more efficiently with less toxic properties.

Hemodynamic Effects of SGLT2 Inhibitors in Patients with and Without Diabetes Mellitus-A Narrative Review.

: The current review aims to present the beneficial effects of SGLT2 inhibitors (dapagliflozin and empagliflozin) on several hemodynamic parameters such as blood pressure, filtration pressure at the level of the glomerular capillaries, and the improvement of the preload and afterload of heart muscle. In order to stop chronic kidney disease (CKD) from progressing, SGLT2 inhibitors have become an important disease-modifying treatment. : Recent clinical studies have shown the success of these drugs in treating heart failure, reducing the risk of cardiovascular events, hospitalization, and mortality.

Antiviral potential and in silico insights of polyphenols as sustainable phytopharmaceuticals: A comprehensive review.

Polyphenols, particularly flavonoids, are reported to have health-promoting, disease-preventing abilities, and several polyphenols have a wide spectrum of antiviral activities that can be explored for preventive and or therapeutic purposes. We have compiled the updated literature of diverse polyphenols active against common viral diseases, including Herpes, Hepatitis, influenza, rota, SARS-corona-viruses, etc. The antiviral activity of bioactive polyphenols depends on the hydroxyl and ester groups of polyphenol molecules, as compounds with five or more hydroxyl groups and three specific methoxy groups showed antiviral potential, like anti-rabies activity.

Exploring B-cell epitope conservation and antigenicity shift in current COVID-19 variants: Analyzing spike-antibody interactions for therapeutic uses.

SARS-CoV-2, responsible for the global COVID-19 pandemic, has undergone significant genetic changes, leading to various variants impacting transmissibility, severity, and vaccine efficacy. The methodology involved evaluating SARS-CoV-2 variants designated by WHO as Variants of Interest (VOIs) and Variants Under Monitoring (VUMs). Several noteworthy mutations including G446S, K417N, T478K, E484A, N501Y, and Y505H exhibit a strong pattern of convergent evolution across all these variants, particularly at antigenic sites within the spike protein.

Facile access to trifluoromethyl propargyl alcohol by metal-free transfer hydrogenation and cyanation of alkynyl ketones.

We report an efficient synthetic route to the metal-free hydroboration and cyanosilylation of a wide range of alkynyl trifluoromethyl ketones using pinacolborane (4,4,5,5-tetramethyl-1,3,2-dioxaborolane) and trimethylsilyl cyanide under mild reaction conditions at ambient temperature. These highly effective hydroboration and cyanosilylation reactions lead to the corresponding alkynyl trifluoromethyl propargyl alcohols after hydrolysis. In addition, trifluoromethyl (CF) group-based pharmaceutically active enflicoxib analogs were synthesized from propargyl alcohol.