The Multitarget Action of Vitamins in the Ischemic Stroke.

A stroke, also known as a cerebral hemorrhage, occurs when there is an interruption in the blood supply to a part of the brain, resulting in damage to brain cells. This issue is one of the leading causes of death in developed countries, currently killing about 5 million people annually. Individuals who survive ischemic stroke often face serious vision problems, paralysis, dementia, and other sequelae. The numerous efforts to prevent and/or treat stroke sequelae seem insufficient, which is concerning given the increasing global elderly population and the well-known association between aging and stroke risk. In this review, we aim to present and discuss the importance of vitamins in stroke prevention and/or incidence. Vitamins from diet or dietary supplements influence the body at various levels; they are a relevant factor but are reported only in isolated articles. This review reports and updates the multitarget role of vitamins involved in reducing stroke risk.

In vitro and in silico evaluation of the anti-leishmania activity of synthetic chalcones.

Leishmaniasis is a group of neglected, vector-borne infectious diseases that affect millions of people around the world. The medications available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated and have serious side effects. In this work, 10 chalcones were synthesised and evaluated in vitro against promastigotes and axenic amastigotes of Leishmania infantum. Compounds CP04 and CP06 were the most promising, respectively presenting IC50 values = 13.64 ± 0.25 and 11.19 ± 0.22 µM against promastigotes, and IC50 = 18.92 ± 0.05 and 22.42 ± 0.05 µM against axenic amastigotes. Only compound CP04 did not show cytotoxicity against peripheral blood mononuclear cells (PBMCs). Molecular docking studies conducted with sterol 14-alpha demethylase (CYP-51) (PDB: 3L4D) and trypanothione reductase (PDB: 5EBK) enzymes from L. infantum evidenced the great affinity of compound CP04 for these targets, presenting Moldock score values of -94.0758 and -50.5692 KJ/mol-1.

Coumarin-Based Compounds as Inhibitors of Tyrosinase/Tyrosine Hydroxylase: Synthesis, Kinetic Studies, and In Silico Approaches.

Cancer represents the main cause of morbidity and mortality worldwide, constituting a serious health problem. In this context, melanoma represents the most aggressive and fatal type of skin cancer, with death rates increasing every year. Scientific efforts have been addressed to the development of inhibitors targeting the tyrosinase enzyme as potential anti-melanoma agents due to the importance of this enzyme in melanogenesis biosynthesis. Coumarin-based compounds have shown potential activity as anti-melanoma agents and tyrosinase inhibitors. In this study, coumarin-based derivatives were designed, synthesized, and experimentally evaluated upon tyrosinase. Compound FN-19, a coumarin-thiosemicarbazone analog, exhibited potent anti-tyrosinase activity, with an IC50 value of 42.16 ± 5.16 µM, being more active than ascorbic acid and kojic acid, both reference inhibitors. The kinetic study showed that FN-19 acts as a mixed inhibitor. Still, for this compound, molecular dynamics (MD) simulations were performed to determine the stability of the complex with tyrosinase, generating RMSD, RMSF, and interaction plots. Additionally, docking studies were performed to elucidate the binding pose at the tyrosinase, suggesting that the hydroxyl group of coumarin derivative performs coordinate bonds (bidentate) with the copper(II) ions at distances ranging from 2.09 to 2.61 Å. Then, MM/PBSA calculations revealed that van der Waals interactions are the most relevant intermolecular forces for complex stabilization. Furthermore, it was observed that FN-19 has a binding energy (ΔEMM) value similar to tropolone, a tyrosinase inhibitor. Therefore, the data obtained in this study will be useful for designing and developing novel coumarin-based analogs targeting the tyrosinase enzyme.