2D-QSAR Modeling and Molecular Docking Studies on 1H-Pyrazole-1-carbothioamide Derivatives as EGFR Kinase Inhibitors.

Epidermal growth factor receptor (EGFR) kinase has been commonly associated with cancers such as lung, ovarian, hormone-refractory prostate, metastatic colorectal, glioblastoma, pancreatic, and breast cancers. A series of 1H-pyrazole-1-carbothioamide derivatives and their EGFR inhibitory activities were subjected to two-dimensional (2D) quantitative structure-activity relationship (2D-QSAR) studies. The 2D-QSAR models were constructed based on a forward selection of partial least-squares (PLS) and stepwise multiple linear regression (SW-MLR) methods validated by leave-one-out (LOO) and external test set prediction approaches. The stepwise multiple linear regression (SW-MLR) method presented an encouraging result as compared to other methods. The results of the study indicated that the activity of 1H-pyrazole-1-carbothioamide derivatives as an EGFR kinase inhibitor was more influenced by adjacency distance matrix descriptors. The models were improved after outlier removal through the applicability domain. Based on the resultant models, 11 new compounds with high potency were designed as EGFR kinase inhibitors. Molecular docking studies were performed for designing compounds, and they were compared with erlotinib as a reference to predict their interactions in the active site and identify structural features necessary for producing biological activities.

Advice from the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons on riot control agents in connection to the Chemical Weapons Convention.

Compounds that cause powerful sensory irritation to humans were reviewed by the Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) in response to requests in 2014 and 2017 by the OPCW Director-General to advise which riot control agents (RCAs) might be subject to declaration under the Chemical Weapons Convention (the "Convention"). The chemical and toxicological properties of 60 chemicals identified from a survey by the OPCW of RCAs that had been researched or were available for purchase, and additional chemicals recognised by the SAB as having potential RCA applications, were considered. Only 17 of the 60 chemicals met the definition of a RCA under the Convention. These findings were provided to the States Parties of the Convention to inform the implementation of obligations pertaining to RCAs under this international chemical disarmament and non-proliferation treaty.