In Vivo Angiogenesis Screening and Mechanism of Action of Novel Tanshinone Derivatives Produced by One-Pot Combinatorial Modification of Natural Tanshinone Mixture from Salvia Miltiorrhiza

摘要: Background Natural products present in low quantity herb medicines constitute an important source of chemical diversity. However, the isolation sufficient amounts these abundant constituents for structural modification has been a challenge several decades and subsequently halts research on utilization this entities drug discovery development. And, pro-angiogenic therapies are being explored as options to treat cardio-cerebral vascular diseases wound healing recently. The study investigates potential tanshinone derivatives produced by one-pot synthesis using zebrafish model. Methodology/Principal Findings In order address difficulty medicines, novel combinatorial was used diversify partially purified mixture from Salvia miltiorrhiza. This led ten new imidazole-tanshinones (Compounds 1–10) one oxazole-tanshinone (Compound 11), structures which were characterized spectroscopic methods combination with single-crystal X-ray crystallographic analysis. angiogenesis activities determined experimental model chemical-induced blood vessels damage zebrafish. Of all tested derivatives, compound 10 exhibited most potent protective restorative activity EC50 value 0.026 µM. Moreover, mechanism underlying pro-angiogenesis effect probably involved VEGF/FGF-Src-MAPK PI3K-P38 signalling pathways gene expression analysis blocking assay pathways-specific kinase inhibitors. Conclusions/Significance Taken together, our demonstrated more distinctive properties than other tanshinones revealed development agent associated insufficient angiogenesis. Our results highlighted great adopting newly modified approach enhance diversity biological natural regardless their abundances.