Synthesis, evaluation and quantitative structure-activity relationship (QSAR) analysis of Wogonin derivatives as cytotoxic agents.

A novel series of 49 wogonin derivatives were synthesized by introducing group at 7-, 8- or B ring of wogonin. The cytotoxic activities against HepG2, A549 and BCG-823 cancer cell lines were also investigated in vitro. Several of them showed obvious cytotoxic activities and compound 3h possessed the highest potency against HepG2, A549, and BCG-823 with IC50 values of 1.07µM, 1.74µM and 0.98µM, respectively. A quantitative structure-activity relationship (QSAR) study of these synthetic derivatives as well as wogonin indicated that high solubility and low octanol/water partition coefficient are favorable, and excessive electrostatic properties and refractivity are unfavorable for the cytotoxic activities of these wogonin derivatives. These findings and results provide a base for further investigations.

Recent discovery of indoleamine-2,3-dioxygenase 1 inhibitors targeting cancer immunotherapy.

There has been great attention on indoleamine-2,3-dioxygenase 1 (IDO1) around cancer immunotherapy because of its role in enabling cancers to evade the immune system. The most recent spurt of high potent IDO1 inhibitors has been driven by the solution of the increased crystal structures of inhibitors with IDO1. Though the structural information of the active site of IDO1 obtained from the crystals are quite similar, the structures of reported potent inhibitors are quite different. Besides, while thousands of bioactive small molecule inhibitors of IDO1 exist, to date, only five compounds have entered clinical trials. In an effort to obtain more clinical drugs targeting IDO1, more comprehensive understanding of the active site of IDO1 and the structures of existing potent IDO1 inhibitors are necessary. Thus, this review mainly focus on the key features reported from specific crystal structures of IDO1 and an overview of the most recently developed IDO1 inhibitors under investigation and their other derived applications which may contribute to a better usage in cancer immunotherapy.

Recent progress of cyclin-dependent kinase inhibitors as potential anticancer agents.

Deregulation of the cell cycle is a common feature in human cancer. The inhibition of cyclin-dependent kinases (CDKs), which play a crucial role in control of the cell cycle, has always been one of the most promising areas in cancer chemotherapy. This review first summarizes the biology of CDKs and then focuses on the recent advances in both broad-range and selective CDK inhibitors during the last 5 years. The design rationale, structural optimization and structure-activity relationships analysis of these small molecules have been discussed in detail and the key interactions with the amino-acid residues of the most important compounds are highlighted. Future perspectives for CDKs inhibitors will be defined in the development of highly selective CDK inhibitors, an accurate knowledge of gene control mechanism and further predictive biomarker research.