Analgesic and anti-inflammatory activity of podophyllotoxin derivatives.

CONTEXT: Podophyllotoxin is a natural product that inhibits the polymerization of tubulin and has served as a prototype for the development of diverse antitumor agents in clinical use, such as etoposide, teniposide and etopophos. Reumacon, another semisynthetic derivative, reached its clinical phase for the treatment of rheumatoid arthritis. OBJECTIVE: This study investigated the analgesic and anti-inflammatory properties of three compound derivatives from podophyllotoxin. MATERIALS AND METHODS: During a phytochemical study performed on Juniperus thurifera Linne (Cupressaceae) leaves, among other products, several cyclolignans, such as podophyllotoxin, deoxypodophyllotoxin, deoxypicropodophyllotoxin and thuriferic acid were isolated. These compounds, obtained afterwards through semisynthesis, were assayed as analgesic and anti-inflammatory agents. Additionally, the cytotoxic activity of thuriferic acid was evaluated in three cancer cell lines, P-388, A-549 and HT-29, and these data were compared with previous cytotoxicity results obtained for the other three compounds. RESULTS: Analgesic activity results showed that deoxypicropodophyllin is as effective as deoxypodophyllotoxin to inhibit nociceptive perception induced by acetic acid in mice (77.8% ± 4.1% and 71.3% ± 6.5%, respectively), while its cytotoxicity [1.01 × 10(-7) (GI50 M)] is 100-fold less. Other set of experiments showed that thuriferic acid, a derivative of podophyllotoxin a thousand times less citotoxic [1.21 × 10(-5) (GI50 M)] than deoxypodophyllotoxin, caused significant inhibition of paw edema development in the carrageenan-induced inflammation test (63.4% ± 3.3%), effect comparable to those of deoxypodophyllotoxin (66.3% ± 4.4%), and the standard drug indomethacin (61.5% ± 2.5%). CONCLUSION: We conclude that deoxypicropodophyllotoxin and thuriferic acid are effective in reducing edema formation. However, deoxypicropodophyllin is more related with analgesic activity than anti-inflammatory effect.

Actividad antifúngica in vitro del aceite esencial de Swinglea glutinosa Merr sobre Colletotrichum sp. patógeno de mango (Mangifera indica L.) / In vitro antifungal activity of the essential oil of Swinglea glutinosa Merr against mango (Mangifera indica L.) pathogen Colletotrichum sp

RESUMEN Se evaluó la actividad antifúngica del aceite esencial de limón de cerca (Swinglea glutinosa) sobre el hongo Colletotrichum sp. aislado de frutos de mango (Mangifera indica L). El aceite esencial, se obtuvo por hidrodestilación de hojas y corteza del fruto, y mediante cromatografía de gases acoplada a espectrometría de masas se determinó la fitoquímica. Se identificaron presuntivamente 41 metabolitos secundarios, siendo los compuestos mayoritarios (β-pineno (31.3 %), α-pineno (15.1%) y germacreno D (14.4 %). El aceite esencial inhibió el crecimiento del hongo en un 31.16 %, 52.77 % y 82.41 % en ensayo de dilución en agar, a las concentraciones de 0.3, 1 y 2 % respectivamente, con diferencias entre todos los tratamientos evaluados (p=0.000). En ensayo de dilución en caldo se registró inhibición de la germinación de esporas de 0, 1 9.47, 41.03 y 100 % (p=0.000) a concentraciones de 0, 2, 4 y 8 μL/mL. Adicionalmente, en ensayo de microatmósfera se presentó una inhibición de máxima de 22,97 % del crecimiento micelial con adición de 20 μL de aceite esencial por caja de Petri (p=0.000). Este trabajo encontró que el aceite esencial de S. glutinosa ejerce inhibición dosis-dependiente sobre el crecimiento micelial y la germinación de esporas de Colletotrichum sp.

ABSTRACT The antifungal activity of the essential oil of Swinglea glutinosa on the fungus Colletotrichum sp. isolated from mango (Mangifera indica L) fruit was evaluated. The essential oil was obtained by hydrodistillation of leaves and fruit rind, and phytochemistry was determined by gas chromatography coupled to mass spectrometry. Forty-one secondary metabolites were presumptively identified, the major compounds being (β-pinene (31.3 %), α-pinene (15.1 %) and germacrene D (14.4 %). The essential oil inhibited fungal growth by 31.16 %, 52.77 % and 82.41 % in agar dilution assay, at concentrations of 0.3, 1 and 2 % respectively, with differences among all treatments evaluated (p=0.000). In the broth dilution test, spore germination inhibition of 0, 19.47, 41.03 and 100 % (p=0.000) was recorded at concentrations of 0, 2, 4 and 8 μL/mL. Additionally, in microatmosphere assay, a maximum inhibition of 22.97 % of mycelial growth was presented with the addition of 20 μL of essential oil per Petri dish. This work found that the essential oil of S. glutinosa exerts dose-dependent inhibition on mycelial growth and spore germination of Colletotrichum sp.