Abstract
Two new series of betulin derivatives with semicarbazone (7a–g) or thiosemicarbazone (8a–g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents.
Highlights
IntroductionCancer has become the second leading cause of human death worldwide [1]. The most effective therapies used in cancer treatment continue to be traditional cytotoxic agents [2]
Nowadays, cancer has become the second leading cause of human death worldwide [1]
The results suggested that the electron-donating substitution with semicarbazone or thiosemicarbazone moiety at the C28 of betulin was beneficial for compounds to displayed remarkable cytotoxicity against MCF-7 cells
Summary
Cancer has become the second leading cause of human death worldwide [1]. The most effective therapies used in cancer treatment continue to be traditional cytotoxic agents [2]. Betulin (BE, lup-20(29)-ene-3β,28-diol, 1) is an important natural lupine-type triterpenoid widely distributed in plenty of plants, especially abundant in the bark of birch trees (Figure 1) [6]. Plenty of studies have reported that betulin and its derivatives have significant antitumor activities against many kinds of cancer cell lines, such as colorectal carcinoma (HT29, HCT116) [16,17], lung carcinoma (A549) [18], liver carcinoma (SK-HEP-1, HepG2) [19,20], breast carcinoma (MCF-7, MDA-MB231) [21], prostate carcinoma (PC3) [22] as well as cervical carcinoma (HeLa) [23] and leukemia (HL-60, K562, U937) [24,25,26]. The high hydrophobicity of betulin hampers its further development as a cytotoxic drug [27,28,29]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
