Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne

• Published in: Phytochemistry (Oxford) 2022-11, Vol.203, p.113395-113395, Article 113395
• Main Authors: Li, Shi-Fei, Wang, Xiu-Yi, Li, Gong-Lu, Jiao, Ying-Ying, Wang, Wen-Hao, Wu, Xing-Kang, Zhang, Li-Wei
• Format: Article
• Language: English
• Subjects: Daphnane-type diterpene; HIV latency-Reversing agent; STAT1; Thymelaeaceae; Tigliane-type diterpene; Wikstroemia chamaedaphne
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2022.113395

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the “shock and kill” of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV. Three undescribed diterpenes were isolated from the leaves of W. chamaedaphne. These compounds displayed strong HIV latency-reversing activity via activating STAT1 activity. [Display omitted] •Three undescribed diterpenes obtained from the leaves of W. chamaedaphne.•Compounds 1 and 2 represents the first A ring cleavage daphnane-type backbone.•3 and 4, like prostratin, showed high potency in activating latent HIV activity.•1 and 3 could promote the phosphorylation of STAT1, but did not affect STAT1.•STAT1 signaling pathway was involved in 1 and 3 activating latent HIV.