Statistical methods for in silico tools used for risk assessment and toxicology

In silico toxicology is one type of toxicity assessment that uses computational methods to visualize, analyze, simulate, and predict the toxicity of chemicals. It is also one of the main steps in drug design. Animal models have been used for a long time for toxicity testing. Animal studies for the type of toxicological information needed are both expensive and time-consuming, and to that, ethical consideration is added. Many different types of in silico methods have been developed to characterize the toxicity of chemical materials and predict their catastrophic consequences to humans and the environment. In light of European legislation such as Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) and the Cosmetics Regulation, in silico methods for predicting chemical toxicity have become increasingly important and used extensively worldwide e.g., in the USA, Canada, Japan, and Australia. A popular problem, concerning these methods, is the deficiency of the necessary data for assessing the hazards. REACH has called for increased use of in silico tools for non-testing data as structure-activity relationships, quantitative structure-activity relationships, and read-across. The main objective of the review is to refine the use of in silico tools in a risk assessment context of industrial chemicals.

Recent Developments of Coumarin-based Hybrids in Drug Discovery

Coumarin scaffold is a highly significant O-heterocycle, namely benzopyran-2-ones, form an elite class of naturally occurring compounds that possess promising therapeutic perspectives. Based on its broad spectrum of biological activities, the privileged coumarin scaffold is applied to medicinal and pharmacological treatments by several rational design strategies and approaches. Structure-activity relationships of the coumarin-based hybrids with various bioactivity fragments revealed significant information toward the further development of highly potent and selective disorder therapeutic agents. The molecular docking studies between coumarins and critical therapeutic enzymes demonstrated mode of action by forming noncovalent interactions with more than one receptor, further rationally confirm information about structure-activity relationships. This review summarizes recent developments relating to coumarin-based hybrids with other pharmacophores aiming to numerous feasible therapeutic enzymatic targets to combat various therapeutic fields, including anticancer, antimicrobic, anti-Alzheimer, anti-inflammatory activities.

Sequential self-reconstruction of localized Mo species in hierarchical carbon/Co–Mo oxide heterostructures for boosting alkaline hydrogen evolution kinetics and durability

Surface self-reconstruction processes in alkaline hydrogen evolution reaction (HER), especially regarding the explicit structure-activity relationships, remain elusive. Here, we first design a hierarchical Co@NCNT/CoMoOx precatalyst constituted by the defective CoMoOx...

Semi-Synthesis, Cytotoxic Evaluation, and Structure—Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity

Brefeldin A (1), a potent cytotoxic natural macrolactone, was produced by the marine fungus Penicillium sp. (HS-N-29) from the medicinal mangrove Acanthus ilicifolius. Series of its ester derivatives 2−16 were designed and semi-synthesized, and their structures were characterized by spectroscopic methods. Their cytotoxic activities were evaluated against human chronic myelogenous leukemia K562 cell line in vitro, and the preliminary structure–activity relationships revealed that the hydroxy group played an important role. Moreover, the monoester derivatives exhibited stronger cytotoxic activity than the diester derivatives. Among them, brefeldin A 7-O-2-chloro-4,5-difluorobenzoate (7) exhibited the strongest inhibitory effect on the proliferation of K562 cells with an IC50 value of 0.84 µM. Further evaluations indicated that 7 induced cell cycle arrest, stimulated cell apoptosis, inhibited phosphorylation of BCR-ABL, and thereby inactivated its downstream AKT signaling pathway. The expression of downstream signaling molecules in the AKT pathway, including mTOR and p70S6K, was also attenuated after 7-treatment in a dose-dependent manner. Furthermore, molecular modeling of 7 docked into 1 binding site of an ARF1–GDP-GEF complex represented well-tolerance. Taken together, 7 had the potential to be served as an effective antileukemia agent or lead compound for further exploration.