Discovery and structure-activity relationship study of novel isoxazole-based small molecules targeting Zika virus infections.

Autor:	Girmay BS; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr.; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology Daejeon 34113 Republic of Korea., Ayele SA; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr.; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology Daejeon 34113 Republic of Korea., Abbas SA; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr.; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology Daejeon 34113 Republic of Korea., Jang SS; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr., Jung E; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr., Shin JS; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr., Han SB; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr.; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology Daejeon 34113 Republic of Korea., Kim H; Infectious Diseases Therapeutic Research Center, Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology Daejeon 34114 Republic of Korea sbhan@krict.re.kr hjinkim@krict.re.kr.; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology Daejeon 34113 Republic of Korea.; School of Pharmacy, Sungkyunkwan University Suwon 16419 Republic of Korea.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2024 Jul 22; Vol. 15 (8), pp. 2792-2805. Date of Electronic Publication: 2024 Jul 22 (Print Publication: 2024).
DOI:	10.1039/d4md00240g
Abstrakt:	The Zika virus (ZIKV), a significant public health threat, is transmitted by Aedes aegypti mosquitoes and is associated with severe neurological disorders, particularly in newborns. Currently, there are no approved vaccines or specific therapeutics for ZIKV. Our study focuses on the identification and optimization of isoxazole-based small molecules, specifically through the structural modification of KR-26827 , to combat ZIKV infections. Among the synthesized derivatives, 7l emerged as the most promising candidate, showing potent antiviral activity against ZIKV strains and an improved safety profile in vitro . This research underlines the potential of 7l for further development as a ZIKV therapeutic agent. Competing Interests: The authors declare no conflicts of interest. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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