Information geometry theory of bifurcations? A covariant formulation.

The conventional local bifurcation theory (CBT) fails to present a complete characterization of the stability and general aspects of complex phenomena. After all, the CBT only explores the behavior of nonlinear dynamical systems in the neighborhood of their fixed points. Thus, this limitation imposes the necessity of non-trivial global techniques and lengthy numerical solutions. In this article, we present an attempt to overcome these problems by including the Fisher information theory in the study of bifurcations. Here, we investigate a Riemannian metrical structure of local and global bifurcations described in the context of dynamical systems. The introduced metric is based on the concept of information distance. We examine five contrasting models in detail: saddle-node, transcritical, supercritical pitchfork, subcritical pitchfork, and homoclinic bifurcations. We found that the metric imposes a curvature scalar R on the parameter space. Also, we discovered that R diverges to infinity while approaching bifurcation points. We demonstrate that the local stability conditions are recovered from the interpretations of the curvature R, while global stability is inferred from the character of the Fisher metric. The results are a clear improvement over those of the conventional theory.

Could we expect new praziquantel derivatives? A meta pharmacometrics/pharmacoinformatics analysis of all antischistosomal praziquantel derivatives found in the literature.

Praziquantel (PZQ) is the first line drug for the treatment of human Schistosoma spp. worm infections. However, it suffers from low activity towards immature stages of the worm, and its prolonged use induces resistance/tolerance. During the last 40 years, 263 PZQ analogues have been synthesized and tested against Schistosoma spp. worms, but less than 10% of them showed significant activity. Here, we propose a rationalization of the chemical space of the PZQ derivatives by a ligand-based approach. First, we constructed an in-house database with all PZQ derivatives available in the literature. This analysis shows a high heterogeneity in the data. Fortunately, all studies include PZQ as a reference, permitting the classification of compounds into three classes according to their activities. Models involving ligand-based pharmacophore and logistic regression were performed. Five physicochemical parameters were identified as the best to explain the biological activity. In the end, we proposed new PZQ derivatives with modifications at positions 1 and 7, we analysed them with our models, and we observed that they can be more active than the previously synthesized derivatives. The main goal of this work was to conduct the most valuable meta-pharmacometrics/pharmacoinformatics analysis with all Praziquantel medicinal chemistry data available in the literature.

Pharmacokinetic and pharmacodynamic predictions of novel potential HIV-1 integrase inhibitors.

Virtual screening docking-based approach has been employed in order to select novel HIV-1 integrase (IN) potential inhibitors in large databases. Toxicity, metabolism and drug-like properties have been analyzed for the most promising compounds, using computational chemistry techniques. Results were compared and discussed with that obtained for a known HIV-1 (IN) inhibitor reported in the literature.