Simalikalactone D, a Potential Anticancer Compound from Simarouba tulae, an Endemic Plant of Puerto Rico

Abstract

Species of the genus Simarouba have been studied because of their antimalarial and antileukemic activities. A group of oxygenated terpenes called quassinoids have been isolated from species of the Simarouba genus, and are responsible for its therapeutic properties. We hypothesized that Simarouba tulae, an endemic plant from Puerto Rico, is a natural source rich in quassinoid compounds with anticancer activity. The leaves were processed and extracted with solvents of different polarities. The extracts were screened for their antiproliferative activity, and it was shown that the chloroform extract was the most active extract. This extract was purified using different chromatographic techniques to afford the quassinoid simalikalactone D (SKD). This compound was further characterized using NMR and X-ray diffraction analysis. A reassessment of original structural assignments for SKD is proposed. SKD showed high cytotoxicity activity, with an IC50 of 55, 58, and 65 nM in A2780CP20 (ovarian), MDA-MB-435 (breast), and MDA-MB-231 (breast) cell lines, respectively. Exposure to SKD led to 15% inhibition of the migration of MDA-MB-231 cells.

Compounds from diverse natural origin against triple‐negative breast cancer: A comprehensive review

“…Simalikalactone D (SKD), a quassinoid extracted from Simarouba tulae , showed strong cytotoxicity in A2780CP20 (ovarian), MDA‐MB‐435, and MDA‐MB‐231 (breast) cell lines. MDA‐MB‐231 cells through the Nrf2 pathway were 15% less likely to migrate after being exposed to SKD (Mendez et al, 2020). Teucrium mascatense, from the family of Lamiaceae or Labiatae , has an active component, IM60, which might cause fast cell death in MCF‐7, HeLa, and MDA‐MB‐231 cells.…”

Recent syntheses and biological profiling of quassinoids

“…Biosynthetically, they are believed to originate from the oxidation of tetracyclic terpenes; for example euphol (3). 2 Further oxidative cleavage generates the seco-nor-picrasane framework of the polyandranes (4).…”

“…Since their isolation and structural elucidation, quassinoids such as quassin (5) and brusatol (7) have been the subject of intensive biological and synthetic studies attributable to their potent biological properties. [3][4][5][6][7][8][9][10][11][12] For example, the quassinoid bruceantin (6) has reached phase II clinical trials for the treatment of metastatic breast cancer and malignant melanoma in 1982 and 1983, respectively. 13,14 Although originally dismissed for its toxic side effects, bruceantin still appears to sustain potential as a viable drug candidate for several cancer types.…”