Compounds displayed activity against T. brucei. A search of QSAR based on 18 Pt(ii)/Pd(ii) complexes was performed. A study in infected mice of the hit compound showed lack of acute toxicity and anti-proliferative effects that extend animal survival.
Searching for prospective agents against infectious diseases, four new ferrocenyl derivatives, [M(L)(dppf)4](PF), with M = Pd(II) or Pt(II), dppf = 1,1'-bis(dipheny1phosphino) ferrocene and HL = tropolone (HTrop) or hinokitiol (HHino), were synthesized and characterized. Complexes and ligands were evaluated against the bloodstream form of T. brucei, L. infantum amastigotes, M. tuberculosis (MTB) sensitive strain and MTB clinical isolates. Complexes showed a significant increase of the anti-T. brucei activity with respect to the free ligands (>28- and >46-fold for Trop and 6- and 22-fold for Hino coordinated to Pt-dppf and Pd-dppf, respectively), yielding IC values < 5 μM. The complexes proved to be more potent than the antitrypanosomal drug Nifurtimox. The new ferrocenyl derivatives were more selective towards the parasite than the free ligands. The Pt compounds were less toxic on J774 murine macrophages (mammalian cell model), than the Pd ones, showing selectivity index values (SI = IC murine macrophage/ICT. brucei) up to 23. Generation of the {M-dppf} compounds lead to a slightly positive impact on the anti-leishmanial potency. Although the ferrocenyl derivatives were more active on sensitive MTB than the free ligands (MIC = 9.88-14.73 μM), they showed low selectivity towards the pathogen. Related to the mechanism of action, the antiparasitic effect cannot be ascribed to an interference of the compounds with the thiol-redox homeostasis of the pathogen. Fluorescence measurements pointed at DNA as a probable target of the new compounds. [Pt(Trop)(dppf)](PF) and [Pt(Hino)(dppf)](PF) could be considered prospective anti-T. brucei agents that deserve further research.
Summary
Lesions of variable size, associated with the hymenomycete Inocutis jamaicensis, a white‐rot fungus, have been observed on the stems of Eucalyptus globulus trees in Uruguay. The aim of this study was to evaluate some ecophysiological characteristics of I. jamaicensis and assess its ability to colonize E. globulus trees of two different seed origins (Geeveston and Jeeralang) and the clone, 334‐1‐AR, obtained by micropropagation (ENCE, Spain). The growth of an I. jamaicensis isolate (MVHC11379) was evaluated at 25°C in a medium with a water potential of 0 (Ψ = 0). The growth rate did not vary significantly with a growth medium pH of between 4 and 7. I. jamaicensis showed no growth at either 5 or 37°C at any pH or Ψ tested. Weight loss of heartwood and sapwood of different plant provenances inoculated with I. jamaicensis under laboratory conditions was evaluated, and significant differences observed. Lignin‐modifying enzyme activity was evaluated in culture medium with or without E. globulus sawdust as substrate or inducer. Laccase activity was observed with sawdust and manganese peroxidase activity with and without sawdust. Only slight activity of aryl‐alcohol oxidase and lignin peroxidase was detected without sawdust. Experimental inoculation with I. jamaicensis of 3‐year‐old Geeveston and Jeeralang, and of 4‐year‐old 334‐1‐AR stems, resulted in successful fungal colonization of 56% of the 334‐1‐AR, 50% of Geeveston and 25% of Jeeralang trees. Only the heartwood was decayed. In 334‐1‐AR, the rotted wood was delimited by a reaction zone. Wood characteristics and the ability of I. jamaicensis to overcome the chemical reactions in the tree could partially explain differences in susceptibility to the fungus among provenances observed under natural and laboratory conditions.
Se evaluó el comportamiento reproductivo de la mandarina “Nova” en el sur de Uruguay. Se utilizaron plantas de 6 años de edad injertadas sobre P. trifoliata (L.) Raf., bajo condiciones de riego localizado, en dos experimentos realizados en una quinta comercial ubicada en Kiyú, departamento de San José (35º LS). Se cuantificó la intensidad de floración, distribución por tipo de brote, cuajado final, dinámica de abscisión, cuajado por tipo de brote e influencia del fruto sobre la floración siguiente. La intensidad de floración fue muy alta, ubicándose entre 90 y 344 flores/100 nudos. Se verificó una asociación directa entre la intensidad de floración y el porcentaje de brotes reproductivos sin hojas. En los niveles más altos de floración, la abscisión durante el período de cuajado fue alta y constante, mientras que para intensidades menores se pudo identificar un pico de abscisión 25 días antes del fin de la caída fisiológica. El cuajado final estuvo asociado al tipo de brote, siendo significativamente superior para los brotes de flor terminal (22%) en relación a inflorescencias (0.4 %), mixtos (1.6%) y flor solitaria (2.0%). Los resultados obtenidos sugieren que la condición de unifloral es más importante que la presencia de hojas en el cuajado de “Nova”. En los niveles superiores a 250 flores/100 nudos el cuajado fue mínimo y la cosecha se vio fuertemente comprometida. El número de frutos por planta disminuyó la intensidad de floración en el ciclo productivo siguiente, aunque dadas las condiciones de bajo rendimiento de los árboles en estudio, ésta se mantuvo en valores considerados altos (mayor a 200 flores/100 nudos). Este comportamiento en las condiciones del sur de Uruguay, ubica a la mandarina “Nova” dentro del grupo de variedades improductivas. Estos resultados se consideran la base para el ajuste de medidas de manejo que permitan optimizar la productividad de esta variedad.
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