Recent Advances of Bioactive Marine Natural Products in Drug Discovery  

作　　者：ZHANG Qun LV Liuxia WANG Wenhui WEI Meiyan GU Yucheng SHAO Changlun 

机构地区：[1]Key Laboratory of Marine Drugs,Ministry of Education of China,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266100,China [2]Laboratory for Marine Drugs and Bioproducts,Qingdao Marine Science and Technology Center,Qingdao 266237,China [3]Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education,College of Chemistry and Chemical Engineering,Hainan Normal University,Haikou 571158,China [4]Syngenta Jealott’s Hill International Research Centre,Bracknell,Berkshire RG426EY,UK

出　　处：《Journal of Ocean University of China》2024年第5期1297-1318,共22页中国海洋大学学报（英文版）

基　　金：supported by the Shandong Province Special Fund ‘Frontier Technology and Free Exploration’ from Laoshan Laboratory (No. 8-01);the National Natural Science Foundation of China (No. 42376116);the Special Funds of Shandong Province for Qingdao National Laboratory of Marine Science and Technology (No. 2022QN LM030003);the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University (No. CMEMR2023-B16);the National Key Research and Development Program of China (No. 2022YFC2601305);the Innovation Center for Academicians of Hainan Province, and the Fundamental Research Funds for the Central Universities (No. 202461059)

摘　　要：Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug development from the marine resources is higher than the industry average.It is a feasible strategy to conduct the discovery of druglead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters.In the search for bioactive MNPs,our group has constructed a biological resources library including more than 1500 strains of fungi.Focusing on the strategy of Blue Drug Library,we have discovered a series of novel MNPs with abundant biological functions.Highly efficient and scalable total synthesis of(+)-aniduquinolone A(44)and pesimquinolone I(48)have been completed,which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies.As a nucleoprotein(NP)inhibitor,QLA(75)possesses significant anti-influenza A virus(IAV)activities both in vitro and in vivo.CHNQD-00803(76)is a potent and selective AMP-activated kinase(AMPK)activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis(MASH)progression.Moreover,we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects.Particularly,as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases(Arf-GEFs)inhibitor prodrug,CHNQD-01255(78)is qualified to be developed as a targeted candidate anticancer drug,which may be promising to apply for cancer immunotherapy.Hence,it is evident that MNPs play an important role in drug development.

关 键 词：marine medicinal organisms natural products marine drug discovery and optimization drug development 

分 类 号：R284[医药卫生—中药学]