2. Academic Validation
  3. Discovery of novel diarylpyrazolylquinoline derivatives as potent anti-dengue virus agents

Discovery of novel diarylpyrazolylquinoline derivatives as potent anti-dengue virus agents

  • Eur J Med Chem. 2017 Dec 1:141:282-292. doi: 10.1016/j.ejmech.2017.10.001.
Jin-Ching Lee 1,  Chin-Kai Tseng 2,  Chun-Kuang Lin 3,  Chih-Hua Tseng 4
Affiliations

Affiliations

  • 1 Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 2 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • 3 Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung, Taiwan; Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei, Taiwan.
  • 4 Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung City 807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan. Electronic address: [email protected].
PMID: 29031073 DOI: 10.1016/j.ejmech.2017.10.001
Abstract

A number of diarylpyrazolylquinoline derivatives were synthesized and evaluated for their anti-dengue virus (DENV) activity. Among them, 6-fluoro-2-(1-(4-fluorophenyl)-3- (4-methoxyphenyl)-1H-pyrazol-5-yl)quinoline (11c), 2-[1,3-bis(4-methoxyphenyl)-1H-pyrazol- 5-yl]-6-fluoroquinoline (12c), and 4-[5-(6-fluoroquinolin-2-yl)-3-(4-methoxyphenyl)-1H-pyrazol- 1-yl]benzenesulfonamide (13c) exhibited approximately 10-folds more active anti-DENV-2 activity (IC50 of 1.36, 1.09 and 0.81 μM, respectively) than that of ribavirin (IC50 = 12.61 μM). Compound 13c was also potent inhibited Other sero-types of DENV. It reduced DENV replication in both viral protein and mRNA levels, and no significant cell cytotoxicity was detected, with greater than 50% viability of Huh-7-DV-Fluc cells at a concentration of 200 μM. Furthermore, compound 13c can effectively protect mice from DENV Infection by reducing disease symptoms and mortality of DENV-infected mice. It represents a potential Antiviral agent to block DENV replication in vitro and in vivo. Structural optimization of the initial lead compound, 13c, and the detailed molecular mechanism of action are ongoing.

Keywords

Anti-dengue virus activity; Dengue virus; Diarylpyrazolylquinoline; Ribavirin.

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