Synthesis, Leishmanicidal, Trypanocidal, Antiproliferative Assay and Apoptotic Induction of (2-Phenoxypyridin-3-yl)naphthalene-1(2H)-one Derivatives.

The coexistence of leishmaniasis, Chagas disease, and neoplasia in endemic areas has been extensively documented. The use of common drugs in the treatment of these pathologies invites us to search for new molecules with these characteristics. In this research, we report 16 synthetic chalcone derivatives that were investigated for leishmanicidal and trypanocidal activities as well as for antiproliferative potential on eight human cancers and two nontumor cell lines. The final compounds 8−23 were obtained using the classical base-catalyzed Claisen−Schmidt condensation. The most potent compounds as parasiticidal were found to be 22 and 23, while compounds 18 and 22 showed the best antiproliferative activity and therapeutic index against CCRF-CEM, K562, A549, and U2OS cancer cell lines and non-toxic VERO, BMDM, MRC-5, and BJ cells. In the case of K562 and the corresponding drug-resistant K562-TAX cell lines, the antiproliferative activity has shown a more significant difference for compound 19 having 10.3 times higher activity against the K562-TAX than K562 cell line. Flow cytometry analysis using K562 and A549 cell lines cultured with compounds 18 and 22 confirmed the induction of apoptosis in treated cells after 24 h. Based on the structural analysis, these chalcones represent new compounds potentially useful for Leishmania, Trypanosoma cruzi, and some cancer treatments.

Synthesis and antimalarial and anticancer evaluation of 7-chlorquinoline-4-thiazoleacetic derivatives containing aryl hydrazide moieties.

Twelve 7-chloroquinoline derivatives were designed and synthesized using the principle of molecular hybridization through the coupling of 2-[2-(7-chloroquinolin-4-ylthio)-4-methylthiazol-5-yl]acetic acid 1 with various benzoyl hydrazines 2a-l. The synthetic compounds were tested as antimalarials. Some of them showed an efficient in vitro activity as inhibitors of ß-hematin formation and an in vivo activity in a murine model, resulting in compounds 8 and 9 as the most active ones with IC50 values of 0.65 ± 0.09 and 0.64 ± 0.16 µM, respectively. The effects of the compounds on the cell viability, cell cycle, and apoptosis induction of A549 and MCF-7 cancer cell lines were also examined. Our data showed that compounds 6 and 12 were the most active agents, decreasing the cell viability of MCF-7 cells with IC50 values of 15.41 and 12.99 µM, respectively. None of the compounds analyzed significantly affected the viability of peripheral blood mononuclear cells. Also, significant induction of apoptosis was observed when both cancer cell lines were incubated with compounds 6 and 12. In MCF-7 cells, treatment with these compounds led to cell cycle arrest in the G0/G1 phase. The results obtained suggest that these structures may be useful in developing new therapies for malaria and cancer treatment.

Actividad farmacológica sobre el sistema nervioso central del extracto etanólico y de la fracción alcaloidal de Valeriana pavonii / Pharmacological activity on central nervous system of the ethanolic extract and the alcaloidal fraction of Valeriana pavonii

En este trabajo se estudió el efecto farmacológico ejercido sobre el sistema nervioso central de una fracción de compuestos de naturaleza alcaloidal obtenidos de Valeriana pavonii. Esta especie se utiliza indistintamente en nuestro medio para los mismos fines de V. officinalis pese a que difieren en su composición química, particularmente en la presencia de compuestos de tipo alcaloidal, aspecto que puede implicar diferencias importantes en sus perfiles farmacodinámico y toxicológico. El estudio mostró que esta fracción posee efectos de tipo anticonvulsivante (modelo de convulsión por electroshock) y antidepresivo (prueba de desesperación conductal inducida por nado forzado) con respuestas mayores que las provocadas por el extracto etanólico. Además, no evidenció actividad sedante, a diferencia del extracto etanólico, propiedad que se adjudica a otro grupo de constituyentes, como flavonoides y terpenoides. Estos resultados apoyan el uso etnobotánico de esta especie, y destacan el papel que metabolitos de tipo alcaloidal parecen desempeñar en los efectos que sobre el sistema nervioso central ejerce V. pavonii.