Anti-zika virus agents and viral RdRp enzymatic inhibitors of derivatives of 5-membered pyrrolo[3,4-b]indol-3(4H)-one and 6-membered pyridazino[4,5-b]indol-4(5H)-one

	Anti-zika virus agents and viral RdRp enzymatic inhibitors of derivatives of 5-membered pyrrolo[3,4-b]indol-3(4H)-one and 6-membered pyridazino[4,5-b]indol-4(5H)-one
	Ge, XT; Zhou, GF; Qian, WY; Wang, N; Li, F; Yang, RH; Yang, LM; Liu, JS; Zheng, CB; Zheng, YT; Zhou, GC
	2026
发表期刊	Eur. J. Med. Chem.
ISSN	0223-5234
卷号	309
摘要	A previously identified Pictet-Spengler reaction product ZFD-10, derived from indole-2-carbophenylhydrazide scaffold, was shown to inhibit ZIKV replication and infection with anti-NS5 RdRp function. Building on this finding, we conducted systematic structural optimization of the indole-2-carbophenylhydrazide framework. In addition to expanding the library of ZFD-10 analogues bearing 2 '-N-linked six-membered pyridazinone rings, we also synthesized a series of 1 '-N-linked five-membered pyrrolidinone derivatives. Several compounds from both series exhibited potent anti-ZIKV activity and inhibited NS5 enzymatic function, as confirmed across multiple experimental assays. These compounds also markedly reduced expression of the viral E protein. Similar to ZFD10, time-of-addition and time-of-withdrawal assays showed that 16 ab primarily blocks ZIKV infection during the late entry stage and RNA synthesis stage. Collectively, these Pictet-Spengler products as antiviral leads provide a strong foundation for advancing anti-zika drug R&D efforts.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14808
专题	科研部门_分子免疫药理学（郑永唐）
推荐引用方式 GB/T 7714	Ge, XT,Zhou, GF,Qian, WY,et al. Anti-zika virus agents and viral RdRp enzymatic inhibitors of derivatives of 5-membered pyrrolo[3,4-b]indol-3(4H)-one and 6-membered pyridazino[4,5-b]indol-4(5H)-one[J]. Eur. J. Med. Chem.,2026,309.
APA	Ge, XT.,Zhou, GF.,Qian, WY.,Wang, N.,Li, F.,...&Zhou, GC.(2026).Anti-zika virus agents and viral RdRp enzymatic inhibitors of derivatives of 5-membered pyrrolo[3,4-b]indol-3(4H)-one and 6-membered pyridazino[4,5-b]indol-4(5H)-one.Eur. J. Med. Chem.,309.
MLA	Ge, XT,et al."Anti-zika virus agents and viral RdRp enzymatic inhibitors of derivatives of 5-membered pyrrolo[3,4-b]indol-3(4H)-one and 6-membered pyridazino[4,5-b]indol-4(5H)-one".Eur. J. Med. Chem. 309(2026).

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