1. Total synthesis of novel D-ring-modiﬁed triptolide analogues: structure–cytotoxic activity relationship studies on the D-ring of triptolide
Bing Zhou, Xiaomei Li, Huanyu Tang, Zehong Miao, Huijin Feng and Yuanchao Li*. Org. Biomol. Chem., 2011, 9, 3176–3179
For a long time, there have been no studies on the structure-activity relationship of the D-ring of triptolide except for two patents, describing some butenolide-modiﬁed triptolide analogues without any biological activity data, and our previous paper, reporting that an analogue (compound 6) with a ﬁve-membered unsaturated lactam ring has the same activity as the natural triptolide. So the structure-activity relationship of the D-ring is still obscure. To explore whether the ﬁve-membered unsaturated lactone ring of triptolide is completely critical to its anticancer activity, compound 3,havinga transposition butenolide, compound 4,which has a furan ring replacing the ﬁve-membered unsaturated lactone ring, and compound 5 without the planar D-ring were synthesized for SAR studies of the D-ring. The SAR studies of these tripolide analogues were performed by using ovary (SK-OV-3) and prostate (PC-3) tumor cells.
2. Computational prediction and experimental validation of low-aﬃnity target of triptolide and its analogues
Xiufeng Liu, Kai Wang, Weijuan Zheng,* Jiahuang Li* and Zi-chun Hua*. RSC Adv.,2015, 5,34572–34579
This study was designed to investigate the potential interactions between NRs and triptolide, triptonide and triptriolide. 12 NRs were first screened through docking calculations to identify the putative molecular targets of triptolide. Then themost likely target ERa-LBD was expressed and purified in vitro. The binding capacities between ERa-LBD and three compounds were determined by Surface Plasmon Resonance (SPR) and Isothermal Titration Calorimetry (ITC) analyses. The results were further validated using reporter gene assays. These data revealed ERa act as a previously unknown binding protein of triptolide and triptonide which may provide valuable information for studying the mechanisms and structure–function relationships of these chemicals in vivo.
3. The role of breast cancer resistance protein (Bcrp/Abcg2) in triptolide-induced testis toxicity
Chunzhu Li, Guozhen Xing, Xinming Qi,* Guangji Wang*. Toxicol. Res.,2015, 4,1260–1268
Preclinical studies have revealed that triptolide has strong eﬀects against cancer, collagen-induced arthritis, skin allograft rejection and bone marrow transplantation. Several derivatives of triptolide have entered human clinical trials for cancer and other diseases. However, the clinical uses of triptolide and its derivatives have been limited by their toxicity. Triptolide induced cumulative testis toxicity in some experimental and clinical research studies. The mechanisms of testicular injury induced by triptolide are not characterized well.