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 The medications available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated and have serious side effects.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.

Pink pepper (Schinus terebinthifolius Raddi) essential oil: phytochemical composition and cytotoxic activity.

Pink pepper (Schinus terebinthifolius Raddi) is a native species native from Central and South America that produces an essential oil (EOpp) with promising applications. This work aimed to investigate the chemical composition and cytotoxic activity of EOpp extracted from unripe (U-EOpp) and ripe (R-EOpp) pink pepper fruits. U-EOpp and R-EOpp were extracted using the hydrodistillation technique and analysed using NMR and GC-MS. U-EOpp and R-EOpp cytotoxic activity was assessed using HL-60 (acute promyelocytic leukemia) and SK-MEL-28 (malignant melanoma) cell lines by MTT assay. Results showed that α-pinene (29.16%), dl-Limonene (20.65%), and ρ-cymene (15.86%) were U-EOpp major components. In addition, l-phellandrene (38.91%), Sylvestrene (23.02%), and α-pinene (21.62%) were R-EOpp major components. U-EOpp showed cytotoxic activity at 37.5 and 18.7 µg/mL for SK-MEL-28 and HL-60, respectively. R-EOpp showed cytotoxic activity for HL-60 at 100 µg/mL. Therefore, EOpp may represent a remarkable source of active natural compounds used in traditional Brazilian medicine.

Antinociceptive, anti-inflammatory and antioxidant activities of the crude ethanolic extract and alkaloid fraction of Waltheria viscosissima A. St. - Hil. (Malvaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The Waltheria viscosissima A. St.- Hil (Malvaceae) is also known as 'Malva branca', has been reported as ethnopharmacologically useful plant containing antinociceptive and anti-inflammatory properties, but scientific evidence is absent. AIM OF THE STUDY: Elucidate the antinociceptive, anti-inflammatory and antioxidant activity of the crude ethanol extract (EEBWa.v) and alkaloid fraction (FAWa.v) of aerial parts of the W. viscosissima in healthy mice with induced inflammation. MATERIALS AND METHODS: EEBWa.v and FAWa.v (50, 100 and 200 mg/kg) and morphine (10 mg/kg) were used in vivo tests of chemical nociception induced by acetic acid (0.6%; 10 mg/kg) and formalin (2.5%) in Swiss male mice. Acute inflammation was induced by carrageenan (1%) in vivo tests and there were several groups tested. The control (inflammation induced without treatment) and the groups treated with EEBWa.v (100 mg/kg), FAWa.v (100 mg/kg) and dexamethasone (2 mg/kg). After this procedure, the animals were euthanized and the peritoneal fluid was collected to evaluate cell migration and redox balance (malondialdehyde - MDA and Total Antioxidant Capacity - TAC). RESULTS: The morphine, EEBWa.v (50 and 100 mg/kg) and FAWa.v (100 mg/kg) significantly reduced the number of abdominal writhes compared to the control group. FAWa.v (100 mg/kg) was superior to FAWa.v (200 mg/kg). In the formalin-induced nociception model (neurogenic phase) EEBWa.v (50 and 200 mg/kg) significantly reduced the number of paw licks. In the inflammatory phase with peripheral action, FAWa.v (100 mg/kg) was superior to EEBWa.v (200 mg/kg). EEBWa.v and FAWa.v (100 mg/kg) proved to be significant for the next experiments. Both samples showed reduction in cell migration, as well as those treated with dexamethasone, in animals with inflammation induced by carrageenan, compared to the untreated group. The redox balance (TAC and MDA) revealed that only EEBWa.v (100 mg/kg) had higher antioxidant potential than the untreated group and the dexamethasone group, p < 0.005 and p < 0.001, respectively. FAWa.v (100 mg/kg) did not show antioxidant activity superior to EEBWa.v. It was also detected that EEBWa.v and FAWa.v (100 mg/kg) failed to inhibit lipid peroxidation. CONCLUSIONS: The W. viscosissima stimulates pain control, which can be mediated by both central and peripheral action. These bioactive compounds showed promising and potential to replace standard medicines. This bioactive effect is statistically similar to morphine and dexamethasone, standard medicines on the market, but with the advantage of antioxidant activity.