In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin.

(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK.

Copaifera duckei Oleoresin and Its Main Nonvolatile Terpenes: In Vitro Schistosomicidal Properties.

In this article, the in vitro schistosomicidal effects of three Brazilian Copaifera oleoresins (C. duckei, C. langsdorffii, and C. reticulata) are reported. From these botanical sources, the oleoresin of C. duckei (OCd) demonstrated to be the most promising, displaying LC50 values of 75.8, 50.6, and 47.2 µg/ml at 24, 48, and 72 h of incubation, respectively, against adult worms of Schistosoma mansoni, with a selectivity index of 10.26. Therefore, the major compounds from OCd were isolated, and the diterpene, (-)-polyalthic acid (PA), showed to be active (LC50 values of 41.7, 36.2, and 33.4 µg/ml, respectively, at 24, 48, and 72 h of incubation). Moreover, OCd and PA affected the production and development of eggs, and OCd modified the functionality of the tegument of S. mansoni. Possible synergistic and/or additive effects of this balsam were also verified when a mixture of the two of its main compounds (PA and ent-labd-8(17)-en-15,18-dioic acid) in the specific proportion of 3:1 (w/w) was tested. The obtained results indicate that PA should be considered for further investigations against S. mansoni, such as, synergistic (combination with praziquantel (PZQ)) and in vivo studies. It also shows that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.

In vitro leishmanicidal activities of sesquiterpene lactones from Tithonia diversifolia against Leishmania braziliensis promastigotes and amastigotes.

Natural compounds represent a rich and promising source of novel, biologically active chemical entities for treating leishmaniasis. Sesquiterpene lactones are a recognized class of terpenoids with a wide spectrum of biological activities, including activity against Leishmania spp. In this work, a sesquiterpene lactone-rich preparation-a leaf rinse extract (LRE) from Tithonia diversifolia-was tested against promastigote forms of L. braziliensis. The results revealed that the LRE is a rich source of potent leishmanicidal compounds, with an LD50 value 1.5 ± 0.50 µg·mL-1. Therefore, eight sesquiterpene lactones from the LRE were initially investigated against promastigote forms of L. braziliensis. One of them did not present any significant leishmanicidal effect (LD50 > 50 µg·mL-1). Another had a cytotoxic effect against macrophages (4.5 µg·mL-1). The five leishmanicidal compounds with the highest level of selectivity were further evaluated against intracellular parasites (amastigotes) using peritoneal macrophages. Tirotundin 3-O-methyl ether, tagitinin F, and a guaianolide reduced the internalization of parasites after 48 h, in comparison with the negative control. This is the first report on sesquiterpene lactones that have potent leishmanicidal effects on both developmental stages of L. braziliensis.