2. Academic Validation
  3. Design, semisynthesis, α-glucosidase inhibitory, cytotoxic, and antibacterial activities of p-terphenyl derivatives

Design, semisynthesis, α-glucosidase inhibitory, cytotoxic, and antibacterial activities of p-terphenyl derivatives

  • Eur J Med Chem. 2018 Feb 25;146:232-244. doi: 10.1016/j.ejmech.2018.01.057.
Xue-Qing Zhang 1,  Xiao-Feng Mou 2,  Ning Mao 2,  Jie-Jie Hao 2,  Ming Liu 2,  Ji-Yong Zheng 3,  Chang-Yun Wang 2,  Yu-Cheng Gu 4,  Chang-Lun Shao 5
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266200, People's Republic of China; State Key Laboratory for Marine Corrosion and Protection, Luoyang Ship Material Research Institute (LSMRI), Qingdao 266061, People's Republic of China.
  • 2 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266200, People's Republic of China.
  • 3 State Key Laboratory for Marine Corrosion and Protection, Luoyang Ship Material Research Institute (LSMRI), Qingdao 266061, People's Republic of China.
  • 4 Syngenta Jealott's Hill International Research Centre, Bracknell, Berkshire, RG42 6EY, United Kingdom.
  • 5 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, People's Republic of China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266200, People's Republic of China; State Key Laboratory for Marine Corrosion and Protection, Luoyang Ship Material Research Institute (LSMRI), Qingdao 266061, People's Republic of China. Electronic address: shaochanglun@163.com.
PMID: 29407953 DOI: 10.1016/j.ejmech.2018.01.057
Abstract

Terphenyllin (1), a naturally abundant p-terphenyl metabolite, was isolated from the coral derived fungus Aspergillus candidus together with four natural analogues 2-5. To evaluate their potency and selectivity, a series of new derivatives of 1 were designed and semisynthesized. They were evaluated for their α-glucosidase inhibitory, cytotoxic, and Antibacterial activities. Compounds 1, 3, 4, 7, 8, 10, 11, 14, 15, 21, 23, 24, 29, 39, and 40 showed significant α-glucosidase inhibitory activity with IC50 values of 4.79-15 μM, which were stronger than that of the positive controls, 1-deoxynojirimycin (IC50 = 192.0 μM) and acarbose (IC50 = 707.9 μM). Compounds 7 and 10 have relatively higher therapeutic indices (CC50/IC50 = 17 and 10, respectively), representing potential promising leads. The Enzyme kinetic studies of compounds 1 and 24 showed a non-competitive inhibition on α-glucosidase with Ki values of 1.50 and 3.45 μM, respectively. Additionally, compounds 14, 21, 26, 29, 32, 35, and 37 were found to exhibit strong cytotoxicity against three tumor cell lines A549 (lung adenocarcinoma epithelial), HeLa (cervical carcinoma), and HepG2 (hepatocellular liver carcinoma) with IC50 values ranging from 0.15 to 5.26 μM. Further study indicated that 32 could induce S-phase arrest in the cell cycle progression.

Keywords

Aspergillus candidus; Cytotoxicity; Semisynthesize; p-Terphenyls; α-Glucosidase inhibitory.

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