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.
Asunto(s)
Diterpenos , Forboles , Estructura Molecular , Diterpenos/farmacología , Diterpenos/química , Antivirales , Ésteres del ForbolRESUMEN
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.
Asunto(s)
Forboles , Estructura Molecular , Diterpenos/química , Antivirales , Ésteres del ForbolRESUMEN
The development of collateral sensitivity agents that are able to modulate P-glycoprotein (P-gp) is the most promising approaches to overcome multidrug resistance (MDR) in cancer. In this study, eight new diterpenoids of jatrophane and ingenane type, 1-8, and three known ones (9-11) were isolated from Euphorbia glomerulans. Their structures were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations. The MDR reversal activity evaluation of these isolates on breast cancer MCF-7/ADR cells demonstrated the four potent MDR modulators (3, 4, 5, and 9) with great chemoreversal ability and low cytotoxicity. The structure-activity relationship (SAR) analysis indicated that the presence of isobutanoyloxy group at C-8 significantly enhance reversal efficiency. Compound 5 exhibited high efficacy (EC50 = 159.5 nM) in reversing MDR resistance, being stronger than verapamil (EC50 = 302.9 nM). The MDR reversal mechanism assays revealed that 5 could promote the accumulation of Rh123 and DOX in drug-resistant cells in a certain dose-dependent manner, and inhibit P-gp transport function. In addition, the possible recognition mechanism of compound 5 and verapamil (VRP) with P-gp was predicted by molecular docking.