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Glycogen synthase kinase-3 (GSK-3) is a multitasking serine/threonine protein kinase, which is associated with the pathophysiology of several diseases such as diabetes, cancer, psychiatric and neurodegenerative diseases. Tideglusib is a potent, selective, and irreversible GSK-3 inhibitor that has been investigated in phase II clinical trials for the treatment of progressive supranuclear palsy and Alzheimer's disease. In the present study, we performed pharmacophore feature-based virtual screening for identifying potent targetspecific GSK-3 inhibitors. We found 64 compounds that show better GSK-3 binding potentials compared with those of Tideglusib. We further validated the obtained binding potentials by performing 20-ns molecular dynamics simulations for GSK-3 complexed with Tideglusib and with the best compound found via virtual screening in this study. Several interesting molecular-level interactions were identified, including a covalent interaction with Cys199 residue at the entrance of the GSK-3 active site. These findings are expected to play a crucial role in the binding of target-specific GSK-3 inhibitors.

Malaria, a life-threatening disease, is caused by parasitic single-celled microorganisms. It is specifically transmitted by the anopheles female mosquito of the Plasmodium family. There are a lot of drugs available in the market to treat this life-challenging disease. Chloroquine, a cheaper molecule that is available worldwide, is one of them. Drug resistance has been observed with chloroquine as well as with some other quinine derivatives and with artemisinin derivatives in the southeast region of Asia in countries like Cambodia, Thailand, Myanmar, and Vietnam country since 1957. After 1970, the drug resistance has been further increased and it has been expanded in several localities of India. Also, antimalarial agents, particularly chloroquine, have so many side effects such as nausea, vomiting, blurred vision, abdominal cramps, diarrhea, headache, appetite loss, deprivation of hearing, skin color change, baldness, reduced body weight, and seizures. Furthermore, this drug cannot be given to pregnant women. Hence, it is the right time to design and develop newer antimalarial agents so that this kind of drug resistance, as well as side effects of the drugs, can be overcome.

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