Індольний алкалоїд еліптицин як ефективна багатоцільова сполука

• Дата: 2022
• Автори: Shvydenko, Kostiantyn V., Grafova, Iryna A., Shvydenko, Tetiana I., Kostyuk, Aleksandr N., Picanço, Neila S., Silva, Luiz F.R., Kropfitsch, Anya, Wyrepkowski, Claudia D.C., Zerbini, Luiz F., Tadei, Wanderli P., Pereira, Antonia M.R.F., Leskelä, Markku, Grafov, Andriy V.
• Формат: Стаття
• Мова: English
• Опубліковано: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2022
• Теми: ellipticine; in vitro; anticancer; antimalarial; antileishmanial activity; фтор; піролізидин; індолізидин; хінолізидинові алкалоїди; стратегія синтезу
• Онлайн доступ: https://bioorganica.com.ua/index.php/journal/article/view/18
• Назва журналу: Ukrainica Bioorganica Acta

First isolated from the tropical plant Oschrosia elliptica, indole alkaloid ellipticine provoked huge interest since it demonstrated antitumor activity was demonstrated along with limited toxic side effects and a complete lack of hematological toxicity. In this work, a five-step Cranwell and Saxton synthesis was used for obtaining ellipticine (Ell). Ellipticine hydrochloride salt (Ell×HCl) was also synthesized. Detailed in vitro studies of anticancer, antimalarial, and leishmanicidal activities were performed. Antiproliferation assay using DU145 cancer cell line treated with Ell showed a consistent reduction in cell proliferation and cell viability when treated with 5 μmol Ell. Anti-proliferation activity was more pronounced for the Ell×HCl solutions. Both the Ell and Ell×HCl revealed moderate activity in vitro against Leishmania amazonensis promastigotes, which is related to insufficient solubility of the drugs. IC50 values of Ell and Ell×HCl were determined in vitro against multidrug resistant Plasmodium falciparum strain K1. The Ell×HCl was shown to be almost three times more potent than the Ell in DMSO. Upon dilution with water, Ell solubility and activity drops down, while the activity and solubility of Ell×HCl is enhanced up to 10 times in 50:50 aqueous DMSO solutions.