New 8-nitroquinolinone derivative displaying submicromolar in vitro activities against both Trypanosoma brucei and cruzi

International audienceAn antikinetoplastid pharmacomodulation study was conducted at position 6 of the 8-nitroquinolin-2(1H)-one pharmacophore. Fifteen new derivatives were synthesized and evaluated in vitro against L. infantum, T. brucei brucei, and T. cruzi, in parallel with a cytotoxicity assay on the human HepG2 cell line. A potent and selective 6-bromo-substituted antitrypanosomal derivative 12 was revealed, presenting EC50 values of 12 and 500 nM on T. b. brucei trypomastigotes and T. cruzi amastigotes respectively, in comparison with four reference drugs (30 nM ≤ EC50 ≤ 13 μM). Moreover, compound 12 was not genotoxic in the comet assay and showed high in vitro microsomal stability (half life >40 min) as well as favorable pharmacokinetic behavior in the mouse after oral administration. Finally, molecule 12 (E° = −0.37 V/NHE) was shown to be bioactivated by type 1 nitroreductases, in both Leishmania and Trypanosoma, and appears to be a good candidate to search for novel antitrypanosomal lead compounds

Hook selectivity models assessment for black spot seabream. Classic and heuristic approaches.

Size selectivity of the deep water longline used in the black spot seabream (Pagellus bogaraveo) fishery in the Strait of Gibraltar was studied with data of four sizes of hooks. Logistic (classic) and Artificial Neural Networks (heuristic) selectivity models were fitted for two experimental fishing trials. Logistic selectivity model was adequate for only one of the two periods analysed and the inferior results obtained with the classical approach were significantly improved by ANNs. These results indicate that in the event that the classic models do not fit well, perhaps due to poor quality of the data (such as a smaller sample size or highly overlapped distributions), the simpler ANNs models, with capacity to combine linear relationships and highly non-linear, are most appropriate to establish the functional relation between variables