In Silico Identification of Multi-Target Ligands as Promising Hit Compounds for Neurodegenerative Diseases Drug Development.

The conventional treatment of neurodegenerative diseases (NDDs) is based on the "one molecule-one target" paradigm. To combat the multifactorial nature of NDDs, the focus is now shifted toward the development of small-molecule-based compounds that can modulate more than one protein target, known as "multi-target-directed ligands" (MTDLs), while having low affinity for proteins that are irrelevant for the therapy. The in silico approaches have demonstrated a potential to be a suitable tool for the identification of MTDLs as promising drug candidates with reduction in cost and time for research and development.

New Potential Pharmacological Targets of Plant-Derived Hydroxyanthraquinones from spp.

The increased use of polyphenols nowadays poses the need for identification of their new pharmacological targets. Recently, structure similarity-based virtual screening of DrugBank outlined pseudopurpurin, a hydroxyanthraquinone from spp., as similar to gatifloxacin, a synthetic antibacterial agent.

Hybrid Classification/Regression Approach to QSAR Modeling of Stoichiometric Antiradical Capacity Assays' Endpoints.

Quantitative structure-activity relationships (QSAR) are a widely used methodology allowing not only a better understanding of the mechanisms of chemical reactions, including radical scavenging, but also to predict the relevant properties of chemical compounds without their synthesis, isolation and experimental testing. Unlike the QSAR modeling of the kinetic antioxidant assays, modeling of the assays with stoichiometric endpoints depends strongly on the number of hydroxyl groups in the antioxidant molecule, as well as on some integral molecular descriptors characterizing the proportion of OH-groups able to enter and complete the radical scavenging reaction. In this work, we tested the feasibility of a "hybrid" classification/regression approach, consisting of explicit classification of individual OH-groups as involved in radical scavenging reactions, and using further the number of these OH-groups as a descriptor in simple-regression QSAR models of antiradical capacity assays with stoichiometric endpoints.

A Comprehensive Evaluation of Sdox, a Promising HS-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors.

Sdox is a hydrogen sulfide (HS)-releasing doxorubicin effective in P-glycoprotein-overexpressing/doxorubicin-resistant tumor models and not cytotoxic, as the parental drug, in H9c2 cardiomyocytes. The aim of this study was the assessment of Sdox drug-like features and its absorption, distribution, metabolism, and excretion (ADME)/toxicity properties, by a multi- and transdisciplinary , , and approach. Doxorubicin was used as the reference compound.

Computational Analysis of Chemical Space of Natural Compounds Interacting with Sulfotransferases.

The aim of this study was to investigate the chemical space and interactions of natural compounds with sulfotransferases (SULTs) using ligand- and structure-based in silico methods. An in-house library of natural ligands (hormones, neurotransmitters, plant-derived compounds and their metabolites) reported to interact with SULTs was created. Their chemical structures and properties were compared to those of compounds of non-natural (synthetic) origin, known to interact with SULTs.