Seco-cyclic phorbol derivatives and their anti-HIV-1 activities

	Seco-cyclic phorbol derivatives and their anti-HIV-1 activities
	Huang, XL; Huang, XS; Li, QR; Ma, MD; Cui, YD; Yang, LM; Wang, HB; Luo, RH; Chen, JL; Yang, JX; Lin, JR; Li, DX; Zheng, YT; Zhang, J
	2024
发表期刊	CHINESE JOURNAL OF NATURAL MEDICINES
ISSN	2095-6975
卷号	22 期号:4 页码:365-374
摘要	Phorbol esters are recognized for their dual role as anti -HIV -1 agents and as activators of protein kinase C (PKC). The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20, C3/C4, and C9 of phorbol. Concurrently, the lipids located at positions C12/C13 are essential for both the anti -HIV -1 activity and the formation of the PKCligand complex. The influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti -HIV -1 activity requires further exploration. This research entailed the hydrolysis of phorbol, producing seco-cyclic phorbol derivatives. The anti -HIV -1 efficacy of these derivatives was assessed, and the affinity constant ( K d ) for PKC-8 protein of selected seco -cyclic phorbol derivatives was determined through isothermal titration calorimetry. The findings suggest that the chemical modification of cyclopropanols could affect both the anti -HIV -1 activity and the PKC binding affinity. Remarkably, compound S11, with an EC50 of 0.27 mu molL -1 and a CC 50 of 153.92 mu molL -1 , demonstrated a potent inhibitory effect on the intermediate products of HIV -1 reverse transcription (ssDNA and 2LTR), likely acting at the viral entry stage, yet showed no affinity for the PKC-8 protein. These results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti -HIV -1 activity.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14205
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	Huang, XL,Huang, XS,Li, QR,et al. Seco-cyclic phorbol derivatives and their anti-HIV-1 activities[J]. CHINESE JOURNAL OF NATURAL MEDICINES,2024,22(4):365-374.
APA	Huang, XL.,Huang, XS.,Li, QR.,Ma, MD.,Cui, YD.,...&Zhang, J.(2024).Seco-cyclic phorbol derivatives and their anti-HIV-1 activities.CHINESE JOURNAL OF NATURAL MEDICINES,22(4),365-374.
MLA	Huang, XL,et al."Seco-cyclic phorbol derivatives and their anti-HIV-1 activities".CHINESE JOURNAL OF NATURAL MEDICINES 22.4(2024):365-374.

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