Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng.
Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1-5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7-12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher's method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2-4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2-hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2-4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS.
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Ya-Nan
YN
An
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Xue
X
Zhang
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Tian-Yuan
TY
Zhang
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Meng-Yue
MY
Zhang
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, People's Republic of China.
Qian-Zhang
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Xiao-Yu
XY
Deng
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, People's Republic of China.
Feng
F
Zhao
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Ling-Juan
LJ
Zhu
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Guan
G
Wang
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Jie
J
Zhang
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Yi-Xuan
YX
Zhang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, People's Republic of China.
Bo
B
Liu
Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.|Institute of Traditional Chinese Medicine &Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.
Xin-Sheng
XS
Yao
D017209:Apoptosis; D018360:Crystallography, X-Ray; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D061986:MCF-7 Cells; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis; D053723:Panax notoginseng; D010407:Penicillium / Q000378:metabolism*; D040901:Proteomics; D058441:Rhizosphere; D012987:Soil
D007783:Lactones; D012987:Soil; D009569:Nitric Oxide