2D/3D-QSAR Model Development Based on a Quinoline Pharmacophoric Core for the Inhibition of Plasmodium falciparum: An In Silico Approach with Experimental Validation.

Malaria is an infectious disease caused by Plasmodium spp. parasites, with widespread drug resistance to most antimalarial drugs. We report the development of two 3D-QSAR models based on comparative molecular field analysis (CoMFA), comparative molecular similarity index analysis (CoMSIA), and a 2D-QSAR model, using a database of 349 compounds with activity against the P. falciparum 3D7 strain. The models were validated internally and externally, complying with all metrics (q2 > 0.5, r2test > 0.6, r2m > 0.5, etc.). The final models have shown the following statistical values: r2test CoMFA = 0.878, r2test CoMSIA = 0.876, and r2test 2D-QSAR = 0.845. The models were experimentally tested through the synthesis and biological evaluation of ten quinoline derivatives against P. falciparum 3D7. The CoMSIA and 2D-QSAR models outperformed CoMFA in terms of better predictive capacity (MAE = 0.7006, 0.4849, and 1.2803, respectively). The physicochemical and pharmacokinetic properties of three selected quinoline derivatives were similar to chloroquine. Finally, the compounds showed low cytotoxicity (IC50 > 100 µM) on human HepG2 cells. These results suggest that the QSAR models accurately predict the toxicological profile, correlating well with experimental in vivo data.

Photochemistry of P,N-bidentate rhenium(i) tricarbonyl complexes: reactive species generation and potential application for antibacterial photodynamic therapy.

In this work, we describe the photoisomerization of facial rhenium(i) tricarbonyl complexes bearing P,N-bidentate pyridyl/phosphine ligands with different chelating rings and anions: RePNBr, RePNTfO, and RePNNBr, which are triggered under irradiation at 365 nm in solutions. The apparent photodegradation rate constants (k app) depend on the coordinating ability of the solvent, being lowest in acetonitrile. The k app value increases as the temperature rises, suggesting a reactive IL excited state thermally populated from the MLCT excited state involved. Using the Eyring equation, positive activation enthalpies (ΔH ≠) accompanied by high negative values for the activation entropy (ΔS ≠) were obtained. These results suggest whatever the P,N-ligand or anion, the reaction proceeds through a strongly solvated or a compact transition state, which is compatible with an associative mechanism for the photoisomerization. A 100-fold decrease in the log10 CFU value is observed for E. coli and S. aureus in irradiated solutions of the compounds, which follows the same tendency as their singlet oxygen generation quantum yield: RePNBr > RePNTfO > RePNNBr, while no antibacterial activity is observed in the darkness. This result indicates that the generation of singlet oxygen plays a key role in the antibacterial capacity of these complexes.

Synthesis of Five Known Brassinosteroid Analogs from Hyodeoxycholic Acid and Their Activities as Plant-Growth Regulators.

Brassinosteroids (BRs) are plant hormones that promote growth in different plant organs and tissues. The structural requirements that these compounds should possess to exhibit this biological activity have been studied. In this work, a series of known BR analogs 5-15, were synthesized starting from hyodeoxycholic acid 4, and maintaining the alkyl side chain as cholic acid or its methyl ester. The growth-promoting effects of brassinolide (1) and synthesized analogs were evaluated by using the rice lamina inclination assay at concentrations ranging from 1 × 10-8-1 × 10-6 M. Our results indicate that in this concentration range the induced bending angle of rice seedlings increases with increasing concentration of BRs. Analysis of the activities, determined at the lowest tested concentration, in terms of BR structures shows that the 2α,3α-dihydroxy-7-oxa-6-ketone moiety existing in brassinolide is required for the plant growing activity of these compounds, as it has been proposed by some structure-activity relationship studies. The effect of compound 8 on cell elongation was assessed by microscopy analysis, and the results indicate that the growth-promoting effect of analog 8 is mainly due to cell elongation of the adaxial sides, instead of an increase on cell number.

White plague-like coral disease in remote reefs of the Western Caribbean.

The health of coral reef communities has been decreasing over the last 50 years, due the negative effects of human activities combined with other natural processes. We present documentation of a White Plague Disease (WPD) outbreak in the Serrana Bank, an isolated Western Caribbean atoll with presumably inexistent pollutant inputs from local human settlements. In addition, this study summarizes seven years of observations on diseased corals in the nearby island of San Andrés, which in contrast is one of the most populated islands of the Caribbean. There was a massive coral mortality in the atoll lagoon (14 degrees 27'53.24", 80 degrees 14'22.27" W, and 12m depth) due to WPD on May 4 of 2003. Seventeen species were found dead or largely affected by the disease. The information resulting from GPS and manta-tow transects revealed that approximately 5.8 ha of reticulate Montastraea spp. patch reefs were lethally affected by the disease in the atoll. On May 8 of the same year we observed and calculated a mean coral cover of 7.03% (SD +/- 2.44), a mean diseased coral tissue cover of 5.5% (SD +/- 1.1) and a 13.4% (SD +/- 8.05) of recently dead coral covered with a thin filamentous algae layer; approximately 73% of mortalities caused by the disease occurred before the end of the outbreak. A rough estimate of 18.9% in recent coral cover reduction can be attributed to WPD. This represents about 82% of the total coral cover decline since 1995. Semi-enclosed environments such as atoll lagoons and the reticulate patch-reefs of Montastraea spp. seem to be particularly vulnerable to this kind of coral disease, which constitute an alert to increase the monitoring of the same kind of atoll environments. The WPD has been present in the area of the nearby island of San Andrés at a low prevalence level, with sporadic increasing peaks of disease proliferation. The peaks observed during 1999 and 2004 comprised increases of 266% and 355% respectively, suggesting an alarming progression of the disease in this area. This study includes new information of the epizoolotiology of White Plague Disease and documents the permanent prevalence and progression of the WPD in the area of San Andres Island.

White plague-like coral disease in remote reefs of the Western Caribbean

The health of coral reef communities has been decreasing over the last 50 years, due the negative effects of human activities combined with other natural processes. We present documentation of a White Plague Disease (WPD) outbreak in the Serrana Bank, an isolated Western Caribbean atoll with presumably inexistent pollutant inputs from local human settlements. In addition, this study summarizes seven years of observations on diseased corals in the nearby island of San Andrés, which in contrast is one of the most populated islands of the Caribbean. There was a massive coral mortality in the atoll lagoon (14°27’53.24", 80°14’22.27" W, and 12m depth) due to WPD on May 4 of 2003. Seventeen species were found dead or largely affected by the disease. The information resulting from GPS and manta-tow transects revealed that approximately 5.8ha of reticulate Montastraea spp. patch reefs were lethally affected by the disease in the atoll. On May 8 of the same year we observed and calculated a mean coral cover of 7.03% (SD± 2.44), a mean diseased coral tissue cover of 5.5% (SD± 1.1) and a 13.4% (SD± 8.05) of recently dead coral covered with a thin filamentous algae layer; approximately 73% of mortalities caused by the disease occurred before the end of the outbreak. A rough estimate of 18.9% in recent coral cover reduction can be attributed to WPD. This represents about 82% of the total coral cover decline since 1995. Semi-enclosed environments such as atoll lagoons and the reticulate patch-reefs of Montastraea spp. seem to be particularly vulnerable to this kind of coral disease, which constitute an alert to increase the monitoring of the same kind of atoll environments. The WPD has been present in the area of the nearby island of San Andrés at a low prevalence level, with sporadic increasing peaks of disease proliferation. The peaks observed during 1999 and 2004 comprised increases of 266% and 355% respectively, suggesting an alarming progression of the disease in this area. This study includes new information of the epizoolotiology of White Plague Disease and documents the permanent prevalence and progression of the WPD in the area of San Andres Island. Rev. Biol. Trop. 58 (Suppl. 1): 145-154. Epub 2010 May 01.

Este trabajo presenta datos sobre un brote de la Enfermedad de Plaga Blanca (EPB) en el banco de Serrana y resume siete años de observaciones de esta enfermedad en la vecina isla de San Andrés (Caribe colombiano). La mortalidad masiva de corales por causa de EPB se observó en la laguna del atolón (14° 27’ 53.24", 80° 14’ 22.27" W, y 12m de profundidad) en mayo 4 de 2003. Se encontraron 17 especies muertas o atacadas por EPB y 5.8Ha de parches de Montastraea spp. fueron letalmente afectadas por la enfermedad. En mayo 8 del mismo año observamos y calculamos una cobertura promedio de coral de 7.03% (SD± 2.44), un promedio de tejido coralino enfermo de 5.5% (SD± 1.1) y un 13.4% (SD± 8.05) de coral recientemente muerto cubierto con una fina capa de algas filamentosas; aproximadamente 73% de la mortalidad a causa de la enfermedad ya había ocurrido antes de que terminara el brote de EPB. La EPB ha estado presente en el área de la vecina isla de San Andrés con un bajo nivel de prevalencia pero con esporádicos picos de proliferación de la enfermedad. Durante 1999 y 2004 se observaron incrementos de prevalencia de 266% y 355% respectivamente. Ambientes semi-cerrados como son las lagunas de los atolones y los arrecifes de parche reticulados de Montastraea spp. parecen ser especialmente vulnerables a este tipo de enfermedades coralinas, lo que constituye una alerta hacia una mayor atención y monitoreo en este tipo de ambientes lagunares en atolones.