Recent Advances of Bioactive Marine Natural Products in Drug Discovery

• Published in: Journal of Ocean University of China 2024-10, Vol.23 (5), p.1297-1318
• Main Authors: Zhang, Qun, Lv, Liuxia, Wang, Wenhui, Wei, Meiyan, Gu, Yucheng, Shao, Changlun
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; ADP; ADP-ribosylation; ADP-ribosylation factor; Antineoplastic drugs; Biochemistry; Biological activity; Cancer immunotherapy; Chemical compounds; Chemical defence; Chemical defense; Chemical ecology; Clinical trials; Defense industry; Drug development; Drugs; Earth and Environmental Science; Earth Sciences; Fungi; Guanine nucleotide exchange factor; Hepatocellular carcinoma; Immunotherapy; In vivo methods and tests; Industrial development; Influenza A; Inhibitors; Kinases; Lead compounds; Marine biology; Marine chemistry; Marine ecology; Marine resources; Metabolic disorders; Metabolism; Meteorology; Natural products; Neoplasms; Nucleotides; Oceanography; Pharmacology; Review; Toxicity testing
• ISSN: 1672-5182; 1993-5021; 1672-5174
• DOI: 10.1007/s11802-024-5975-4

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 drug-lead 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.