Strigolactones (SLs) are a novel class of plant hormones with enormous potential for the prevention and treatment of inflammation. To further investigate the anti-inflammatory activities of SLs, a representative SL, GR24, and the reductive products of its D-ring were synthesized and their anti-inflammatory activities were fully evaluated on both and models. Among these compounds, the two most active optical isomers ( and ) demonstrated strong inhibitory activity on the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) by blocking the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways; they also greatly inhibited the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae. These results identified the promising anti-inflammatory effects of SLs, and suggested that both the absolute configuration of SL and the α,β-unsaturated D-ring structure are essential for the observed anti-inflammatory activity.

Several small-molecule CDK inhibitors have been identified, but none have been approved for clinical use in the past few years. A new series of 4-[(3-hydroxybenzylamino)-methylene]-4H-isoquinoline-1,3-diones were reported as highly potent and selective CDK4 inhibitors. In order to find more potent CDK4 inhibitors, the interactions between these novel isoquinoline-1,3-diones and cyclin-dependent kinase 4 was explored via in silico methodologies such as 3D-QSAR and docking on eighty-one compounds displaying potent selective activities against cyclin-dependent kinase 4. Internal and external cross-validation techniques were investigated as well as region focusing, bootstraping and leave-group-out. A training set of 66 compounds gave the satisfactory CoMFA model (q 2 = 0.695, r 2 = 0.947) and CoMSIA model (q 2 = 0.641, r 2 = 0.933). The remaining 15 compounds as a test set also gave good external predictive abilities with r 2 pred values of 0.875 and 0.769 for CoMFA and CoMSIA, respectively. The 3D-QSAR models generated here predicted that all five parameters are important for activity toward CDK4. Surflex-dock results, coincident with CoMFA/CoMSIA contour maps, gave the path for binding mode exploration between the inhibitors and CDK4 protein. Based on the QSAR and docking models, twenty new potent molecules have been designed and predicted better than the most active compound 12 in the literatures. The QSAR, docking and interactions analysis expand the structure-activity relationships of constrained isoquinoline-1,3-diones and contribute towards the development of more active CDK4 subtype-selective inhibitors.