Abstrakt
Trilobolide (Tb), a potent natural counterpart of thapsigargin, is a sesquiterpene lactone of guaianolide type isolated from horse caraway (Laser trilobum, L. Borkh).
Since it is well known that porphyrins are preferentially taken up by cancer cells, we have designed and synthesized novel Tb-porphyrin conjugates. Copper-catalyzed azide-alkyne cycloaddition was used to link Tb with porphyrin at once.
Two model conjugates of Tb and porphyrin were synthesized and properly characterized. Employing naturally occurring fluorescence properties of porphyrins, we investigated the intracellular localization of the conjugates employing fluorescence microscopy in living cells.
Intriguingly, the prepared conjugates localized both in mitochondria and lysosomes of HeLa and LNCaP cells. Furthermore, the cytotoxicity of Tb-porphyrin conjugates was assessed in a number of human cancer cell lines and rat peritoneal cells.
Likewise in cancer cell lines, viability of rat peritoneal cells was not affected by the tested conjugates. Interestingly, we observed dose-dependent nitric oxide (iNOS) production induced by the tested conjugates.
The effect was related to the type of a linker used and the overall size of the molecule. the results presented here indicate notable immunobiological potential of the prepared Tb conjugates.