New Diterpenes Isolated from the Colombian Caribbean Soft Coral Pseudoplexaura flagellosa and Their Cytotoxic Properties

Abstract

Studies about secondary metabolites isolated from soft corals around the world have proven the potential of these organism as producers of compounds with a potent cytotoxic activity. In this work, we obtained the extract of Pseudoplexaura flagellosa collected in Santa Marta, Colombia, the cytotoxic activity of this extract, fractions and compounds was established against SiHa (ATCC® HTB-35™), MDA-MB-231 (ATCC® HTB26™), A549 (ATCC® CRM-CCL-185™), PC3 (ATCC® CRL1435), and L929 (ATCC® CCL1™) cell lines. The results showed that the extract of soft coral P. flagellosa has cytotoxic activity with an IC50 of 35.4, 72.3, 49.8 and 40.5 μg/mL against SiHa, A549, PC3 and MDA-MB-231 cell lines, respectively. Thus, this extract was repeatedly subjected to different chromatographic columns and final purification of these fractions afforded pure compounds 1 – 4, which were elucidated by 1D and 2D NMR experiments including 1H, 13C, COSY, HSQC, HMBC and NOESY, and HRESIMS. In addition, Mosher method was used to establish the stereochemistry of compound 2 and chemical interconversion allow establishing the stereochemistry of compound 1. These results let to conclude that compound 2 is a new stereoisomers of acetylated asperdiol previously reported on literature. Additionally, three analogues 5, 6, and 7 were synthesized from compound 1 and the cytotoxic activity of all compounds was evaluated using doxorubicin as positive control. The results showed that 6 (IC50 of 19.3, 23.7, 13.4 and 18.7 μg/mL against SiHa, A549, PC3 and MDA-MB-231, respectively) was the most active compound against all the cancer cell lines.