Alkaloids with Cardiovascular Effects from the Marine-Derived Fungus Penicillium expansum Y32.
Three new alkaloids (1, 4 and 8), together with nine known analogues (2, 3, 5-7, and 9-12), were isolated from the marine-derived fungus Penicillium expansum Y32. Their structures including the absolute configurations were elucidated by spectroscopic and Mosher's and Marfey's methods, along with quantum electronic circular dichroism (ECD) calculations. Each of the compounds was evaluated for cardiovascular effects in a live zebrafish model. All of the compounds showed a significant mitigative effect on bradycardia caused by astemizole (ASM) in the heart rate experiments. Compounds 4-6 and 8-12 exhibited potent vasculogenetic activity in vasculogenesis experiments. This is the first study to report that these types of compounds show cardiovascular effects in zebrafish. The results suggest that these compounds could be promising candidates for cardiovascular disease lead compounds.
Key Lab of Marine Bioactive Substances, First Institute of Oceanography, State Oceanic Administration, Qingdao 266061, China. fanyaqin.826@163.com.
Ya-Qin
YQ
Fan
Key Lab of Marine Bioactive Substances, First Institute of Oceanography, State Oceanic Administration, Qingdao 266061, China. lipeihaihg@sina.com.
Pei-Hai
PH
Li
Key Lab of Marine Bioactive Substances, First Institute of Oceanography, State Oceanic Administration, Qingdao 266061, China. yaxichao@163.com.
Ya-Xi
YX
Chao
Key Lab of Marine Bioactive Substances, First Institute of Oceanography, State Oceanic Administration, Qingdao 266061, China. hchen@fio.org.cn.
Hao
H
Chen
Key Lab of Marine Bioactive Substances, First Institute of Oceanography, State Oceanic Administration, Qingdao 266061, China. duning@fio.org.cn.
Ning
N
Du
Institute of Biology, Shandong Academy of Sciences. heqiuxia8008@163.com.
Qiu-Xia
QX
He
Institute of Biology, Shandong Academy of Sciences. hliukch@keylab.net.
Ke-Chun
KC
Liu
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D016589:Astemizole / Q000494:pharmacology; D001919:Bradycardia / Q000188:drug therapy*; D002317:Cardiovascular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002942:Circular Dichroism; D006339:Heart Rate / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010407:Penicillium / Q000378:metabolism*; D064210:Secondary Metabolism; D015027:Zebrafish
D000470:Alkaloids; D002317:Cardiovascular Agents; D016589:Astemizole
Penicillium expansum; alkaloids; cardiovascular effects; marine-derived fungus; secondary metabolites