Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B
AbstractIn an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis) was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds. View Full-Text
- Supplementary File 1:
Supplementary (DOCX, 3309 KB)
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
Harper, J.L.; Khalil, I.M.; Shaw, L.; Bourguet-Kondracki, M.-L.; Dubois, J.; Valentin, A.; Barker, D.; Copp, B.R. Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B. Mar. Drugs 2015, 13, 5102-5110.
Harper JL, Khalil IM, Shaw L, Bourguet-Kondracki M-L, Dubois J, Valentin A, Barker D, Copp BR. Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B. Marine Drugs. 2015; 13(8):5102-5110.Chicago/Turabian Style
Harper, Jacquie L.; Khalil, Iman M.; Shaw, Lisa; Bourguet-Kondracki, Marie-Lise; Dubois, Joëlle; Valentin, Alexis; Barker, David; Copp, Brent R. 2015. "Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B." Mar. Drugs 13, no. 8: 5102-5110.