Selenium-Containing (Hetero)Aryl Hybrids as Potential Antileishmanial Drug Candidates: In Vitro Screening against L. amazonensis.

Leishmaniasis remains a significant global health concern, with current treatments relying on outdated drugs associated with high toxicity, lengthy administration, elevated costs, and drug resistance. Consequently, the urgent need for safer and more effective therapeutic options in leishmaniasis treatment persists. Previous research has highlighted selenium compounds as promising candidates for innovative leishmaniasis therapy. In light of this, a library of 10 selenium-containing diverse compounds was designed and evaluated in this study. These compounds included selenium-substituted indole, coumarin, chromone, oxadiazole, imidazo[1,2-a]pyridine, Imidazo[2,1-b]thiazole, and oxazole, among others. These compounds were screened against Leishmania amazonensis promastigotes and intracellular amastigotes, and their cytotoxicity was assessed in peritoneal macrophages, NIH/3T3, and J774A.1 cells. Among the tested compounds, MRK-106 and MRK-108 displayed the highest potency against L. amazonensis promastigotes with reduced cytotoxicity. Notably, MRK-106 and MRK-108 exhibited IC50 values of 3.97 µM and 4.23 µM, respectively, and most of the tested compounds showed low cytotoxicity in host cells (CC50 > 200 µM). Also, compounds MRK-107 and MRK-113 showed activity against intracellular amastigotes (IC50 18.31 and 15.93 µM and SI 12.55 and 10.92, respectively). In conclusion, the identified selenium-containing compounds hold potential structures as antileishmanial drug candidates to be further explored in subsequent studies. These findings represent a significant step toward the development of safer and more effective therapies for leishmaniasis, addressing the pressing need for novel and improved treatments.

Evaluation of the scientific activity of the leaf of the species Campomanesia pubescens in wound model infected by Staphylococcus aureus

There is an increasing interest in the use of herbal remedies as healing agents, due to their lower cost in relation to other drugs and the vast Brazilian fauna. The objective of this research was to evaluate the cicatrization effect of the guariroba leaf (Campomanesia pubescens) on the healing of infected wounds. We used 45 Wistar rats, distributed in five groups (n = 9) all with surgically induced skin injury, differing in the presence of contamination and treatment, with evaluation periods of 3, 7 and 14 days, being: G1- negative control without contamination, treated with Physiological Solution 0.9%; G2- control with contamination, treated with Physiological Solution 0.9%; G3 negative with contamination, treated with Carbopol in 0.5% gel; G4- positive control with contamination, treated with Colagenase at 0.6 U / g + 0.01 g Chloramphenicol; G5- positive test with contamination treated with Campomanesia pubescens at 3%, whose vehicle was Carbopol at 0.5%. The wound was made with a metal punch 8 mm in diameter, and a cutaneous fragment was removed from the animals' backs and wound infection was applied to S. aureus in groups G2 to G5. Euthanasia was performed for a lethal dose of anesthetic, and the edges of the wounds were removed for histopathological study. The fibrinoleukocytic crust was present in all animals in the groups of 3, 7 and 14 days. The contraction of the wound was also evaluated, and all groups showed low percentage of wound regression in the 3-day treatment and with 14 days presented a high percentage of regression. Of the 5 groups, the only one that presented complete epithelialization was G5. Of the 5 groups, the ones with the best epithelialization were G4 and G5. The group with the highest amount of mature collagen fibers was G4, followed by G5, and the one with the highest proportion of immature fibers was G1. At the end of the experiment, G4 was the group that gained the most weight and G1 the one that had the lowest weight gain. Guariroba leaf extract (Campomanesia pubescens) was able to promote healing in infected skin wounds similar to the group treated with antibiotics.

The effect of Sebastiania hispida gel on wound model infected by methicillin resistant Staphylococcus aureus.

Medicinal plants are an alternative for the treatment of infected wounds. The objective of this study was to evaluate the efficacy of Sebastiania hispida in an animal model with a wound infected by Staphylococcus aureus. The crude ethanol extract (ExtEtOH) of S. hispida underwent phytochemical analysis, quantification of metabolites and antibacterial activity analysis performed using S. aureus. Wistar rats were used to test healing activity, and the groups evaluated comprised gels of ExtEtOH at the concentrations 0.2 and 2% compared with control groups. Animals were inoculated with the bacteria S. aureus resistant to methicillin. The treatment periods were of 3 and 21 days. Macroscopic and microscopic analysis were conducted and data were submitted to analysis of variance (p < 0.05). Phytochemical and quantification analysis indicated that phenolic compounds and flavonoids are the major constituents, followed by tyterpenes. ExtEtOH 0.2% was the most effective gel against the growth of strains of S. aureus. Histological wound and regression analysis showed that ExtEtOH gels (0.2% and 2%) were similar and effective in promoting wound healing. In the quantification of collagen fibers, the animals from all groups showed a high amount of thick collagen fibers. Thus, ExtEtOH gels based on the shoots of S. hispida can be used for the treatment of infected wounds as a complementary therapy for infected wound closure and further assays are required with other means. The healing effectiveness may be due to the high content of phenolics, flavonoids and triterpenes.