RESUMEN

Tigliane type macrocyclic diterpenoids with special structures and diverse bioactivities are mainly extracted from plants of Euphorbiaceae and Thymelaeaceae. According to the different functional groups, they can be classified into types of phorbol esters, C-4 deoxyphorbol esters, C-12 deoxyphorbol esters, C-16 or C-17 substituted phorbol esters and others. Most of them present promising antiviral activities and cytotoxic activities and are expected to be developed as candidates for anti-AIDS, anti-tuberculosis, and anti-tumor clinical trials, demonstrating great potential for the application in healthcare. This paper reviews 115 novel tigliane-type diterpenoids discovered since 2013 and summarize their chemical structures and bioactivities, aiming to lay a foundation for further development and utilization of these compounds and provide new ideas for the development of clinical drugs.

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RESUMEN

Two new tigliane- and daphnane-type diterpenoids, given the trivial names daphnegens A-B (1-2) were isolated from the buds of Daphne genkwa. Their structures were assigned on the basis of extensive spectroscopic. The absolute configurations of both compounds were determined by comparison of their calculated and experimental CD curves. In addition, compounds 1-2 were tested for their cytotoxic activities against MCF-7 and HepG-2 human cancer cell lines, and compound 2 showed remarkable cytotoxic activity against HepG-2 cell line with the IC50 value of 11.5 µM.

RESUMEN

Tigliane type macrocyclic diterpenoids with special structures and diverse bioactivities are mainly extracted from plants of Euphorbiaceae and Thymelaeaceae. According to the different functional groups, they can be classified into types of phorbol esters, C-4 deoxyphorbol esters, C-12 deoxyphorbol esters, C-16 or C-17 substituted phorbol esters and others. Most of them present promising antiviral activities and cytotoxic activities and are expected to be developed as candidates for anti-AIDS, anti-tuberculosis, and anti-tumor clinical trials, demonstrating great potential for the application in healthcare. This paper reviews 115 novel tigliane-type diterpenoids discovered since 2013 and summarize their chemical structures and bioactivities, aiming to lay a foundation for further development and utilization of these compounds and provide new ideas for the development of clinical drugs.

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RESUMEN

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-5ß-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5ß-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.

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Objective: To study the anti-hepatitis B virus diterpenoids from flowers of Wikstroemia chamaedaphne. Methods: The chemical constituents of the plant were isolated and purified by column chromatography and their structures were elucidated on the basis of physicochemical properties, X-ray, and spectral data. The antivirus assay was tested by MTT and ELISA methods. Results: Six daphnane-type diterpenoids and one tigliane-type diterpenoid were obtained and determined as simplexin (1), pimelotide A (2), pimelotide C (3), wikstroelide E (4), pimelea factor S6 (5), pimelea factor S7 (6), and 6α,7α-epoxy-5β-hydroxy-12-deoxyphorbol-13-decanoate (7), along with two flavonoid glycosides luteolin-4'-O-β-D-glucoside (8) and isoquercitrin (9). Compounds 1-4 and 7 showed certain cytotoxicity on HepG2.2.15 and compound 3 exhibited strong anti-hepatitis B virus activities with IC50 value of 0.016 μg/mL against HBV surface antigen (HBsAg), with TI (Therapeutic Index) value of 355.63. Conclusion: Compounds 7 and 8 are isolated from the genus for the first time. And it is the first time to report the X-ray structure of compound 2 and the anti-hepatitis B virus activity of compound 3 (pimelotide C).

RESUMEN

The cytotoxic chloroform fraction of Euphorbia aellenii Rech. F. (Euphorbiaceae) afforded two new phorbol diterpenoids: 4-deoxy-4α-phorbol-12-(2,3-dimethyl) butyrate-13-isobutyrate and 17-hydroxy-4-deoxy-4α-phorbol-12-(2,3-dimethyl) butyrate-13-isobutyrate. Their structures were elucidated by NMR and other spectroscopic methods. The immunomodulating potentials of the isolated compounds were tested using standard proliferation and chemiluminescence assays. Compound 2 showed moderate inhibitory activity against both T-cell proliferation and reactive oxygen species (ROS) production in whole blood with IC50 of 14.0 ± 0.57 and 44.1 ± 3.8 µg/ml, respectively, while compound 1 was relatively inactive with IC50 >50 µg/mL for T-cell proliferation, and >100 µg/mL for ROS.