Synthesis and cytotoxic activity evaluation of dihydrocucurbitacin B and cucurbitacin B derivatives

Abstract

Two cucurbitacins, dihydrocucurbitacin B (1) and cucurbitacin B (2), which can be obtained in large amounts from the roots of Wilbrandia ebracteata and from the fruits of Luffa operculata, respectively, were used as starting materials for the preparation of a library of 29 semi-synthetic derivatives. The structural changes that were performed include the removal, modification or permutation of functional groups in rings A and B as well as in the side chain. All new semisynthetic compounds, as well as 1 and 2, were tested in vitro for their cytotoxic effects on non-small-cell lung cancer cells (A549 cells). Some of these compound displayed potent to moderate activity against A549 tumor cells, especially those cucurbitacin B derivatives which were modified at ring A.

In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B

“…Cucurbitacins are a group of diverse highly oxygenated triterpenoid molecules predominantly found in different species of the Cucurbitaceae family. They are derived from the cucurbitane skeleton [19-(10→9β)-abeo-10α-lanost-5-ene], which is known for having biological activities including anti-inflammatory, anti-pyretic, analgesic, and hepatoprotective actions [ 14 , 18 ] but the most relevant effects of these molecules are, without doubt, their cytotoxic effects toward a number of human cancer cell lines such as those of the breast [ 19 ], lung [ 20 – 22 ], prostate [ 23 , 24 ], and human colon [ 25 , 26 ].…”

25-O-acetyl-23,24-dihydro-cucurbitacin F induces cell cycle G2/M arrest and apoptosis in human soft tissue sarcoma cells

“…Along with sustained cell growth, evasion from apoptosis is critical for tumor growth and a hallmark of cancer. Survivin, a member of the inhibitor of apoptosis protein family (IAP) is a key regulator of both, cell division and the inhibition of apoptosis, and is highly expressed in various tumor types (Lang et al, 2012;Ríos et al, 2012).…”

Cucurbitacin D Is a Disruptor of the HSP90 Chaperone Machinery

“…Even though this is not the first report of the oxidation of the α-hydroxyketone to a diosphenol moiety for cucurbitacins, 39–41 this is the first example of the transformation via a Saegusa oxidation (Scheme 1) 42–45 . This result can be rationalized via the ability of cucurbitacins to isomerize to form the intermediate enediol, which can be trapped and oxidized to the final diosphenol product.…”