Multi-target QSPR assemble of a Complex Network for the distribution of chemicals to biphasic systems and biological tissues
Abstract Chemometrics, that based prediction on the probability of chemical distribution to different systems, is highly important for physicochemical, environmental, and life sciences. However, the amount of information is huge and difficult to analyze. A multi-system partition Complex Network (MSP-CN) may be very useful in this sense. We define MSP-CNs as large graphs composed by nodes (chemicals) interconnected by arcs if a pair of chemicals have similar partition in a given system. Experimental quantification of partition in many systems is expensive, so we can use a Quantitative Structure–Partition Relationship (QSPR) model. Unfortunately, with classic QSPR we need to use one model for…
Generalized Molecular Descriptors Derived From Event-Based Discrete Derivative.
In the present study, a generalized approach for molecular structure characterization is introduced, based on the relation frequency matrix (F) representation of the molecular graph and the subsequent calculation of the corresponding discrete derivative (finite difference) over a pair of elements (atoms). In earlier publications (22- 24), an unique event, named connected subgraphs, (based on the Kier-Hall's subgraphs) was systematically employed for the computation of the matrix F. The present report is a generalization of this notion, in which eleven additional events are introduced, classified in three categories, namely, topological (terminal paths, vertex path incidence, quantum subgrap…
Provisional Classification and in Silico Study of Biopharmaceutical System Based on Caco-2 Cell Permeability and Dose Number
Today, early characterization of drug properties by the Biopharmaceutics Classification System (BCS) has attracted significant attention in pharmaceutical discovery and development. In this direction, the present report provides a systematic study of the development of a BCS-based provisional classification (PBC) for a set of 322 oral drugs. This classification, based on the revised aqueous solubility and the apparent permeability across Caco-2 cell monolayers, displays a high correlation (overall 76%) with the provisional BCS classification published by World Health Organization (WHO). Current database contains 91 (28.3%) PBC class I drugs, 76 (23.6%) class II drugs, 97 (31.1%) class III d…
Harmonization of QSAR Best Practices and Molecular Docking Provides an Efficient Virtual Screening Tool for Discovering New G-Quadruplex Ligands
Telomeres and telomerase are key players in tumorogenesis. Among the various strategies proposed for telomerase inhibition or telomere uncapping, the stabilization of telomeric G-quadruplex (G4) structures is a very promising one. Additionally, G4 stabilizing ligands also act over tumors mediated by the alternative elongation of telomeres. Accordingly, the discovery of novel compounds able to act on telomeres and/or inhibit the telomerase enzyme by stabilizing DNA telomeric G4 structures as well as the development of approaches efficiently prioritizing such compounds constitute active areas of research in computational medicinal chemistry and anticancer drug discovery. In this direction, we…