Series of novel triterpenoid hybrids were designed and synthesized by introducing 2-aminobenzamide moiety at C28 position of triterpenoid derivatives. Thirteen new conjugates were thus successfully prepared and evaluated as cytotoxic agents, revealing an interesting anticancer activity in KB and HepG2 cancer cell lines.
TsogoevaS.B. (2010) Recent progress in the development of synthetic hybrids of natural or unnatural bioactive compounds for medicinal chemistry. Mini Reviews in Medicinal Chemistry, 10, 773–793.
2.
TietzeL.F., BellH.P., ChandrasekharS. (2003) Natural product hybrids as new leads for drug discovery. Angewandte Chemie International Edition, 42, 3996–4028.
3.
MehtaG., SinghV. (2002) Hybrid systems through natural product leads: an approach towards new molecular entities. Chemical Society Reviews, 31, 324–334.
BaglinI., Mitaine-OfferA.C., NourM., TanK., CaveC., Lacaille-DuboisM.A. (2003) A review of natural and modified betulinic, ursolic and echinocystic acid derivatives as potential antitumor and anti-HIV agents. Mini Reviews in Medicinal Chemistry, 3, 525–539.
6.
CichewiczR.H., KouziS.A. (2004) Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Medicinal Research Reviews, 24, 90–114.
YogeeswariP., SriramD. (2005) Betulinic acid and its derivatives: a review on their biological properties. Current Medicinal Chemistry, 12, 657–666.
9.
AlakurttiS., MakelaT.S., KoskimiesS., Yli-KauhaluomaJ. (2006) Pharmacological properties of the ubiquitous natural product betulin. European Journal of Pharmaceutical Sciences, 29, 1–13.
10.
DzubakP., HajduchM., VydraD., HustovaA., KvasnicaM., BiedermannD., MarkovaL., SarekJ. (2006) Pharmacological activities of natural triterpenoids and their therapeutic implications. Natural Product Reports, 23, 394–411.
11.
DangZ., HoP., ZhuL., QianK., LeeK.H., HuangL., ChenC.H. (2013) New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1. Journal of Medicinal Chemistry, 56, 2029–2037.
12.
LiH., HeN., LiX., ZhouL., ZhaoM., JiangH., ZhangX. (2013) Oleanolic acid inhibits proliferation and induces apoptosis in NB4 cells by targeting PML/RARα. Oncology Letters, 6, 885–890.
13.
RashidS., DarB.A., MajeedR., HamidA., BhatB.A. (2013) Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents. European Journal of Medicinal Chemistry, 66, 238–245.
14.
LaszczykM.N. (2009) Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Medica, 75, 1549–1560.
15.
TolstikovaT.G., SorokinaI.V., TolstikovG.A., FlekhterO.B. (2006) Biological activity and pharmacological prospects of lupane terpenoids: I. Natural lupane derivatives. Russian Journal of Bioorganic Chemistry, 32, 37–49.
16.
SamiA., TaruM., SalmeK., JariY.K. (2006) Pharmacological properties of the ubiquitous natural product betulin. European Journal of Pharmaceutical Sciences, 29, 1–13.
17.
QiaoZ. (2013) Chidamide, a novel histone deacetylase inhibitor, synergistically enhances gemcitabine cytotoxicity in pancreatic cancer cells. Biochemical and Biophysical Research Communications, 434, 95–101.
18.
PauerL.R., OlivaresJ., CunninghamC., WilliamsA., GroveW., KrakerA., OlsonS., NemunaitisJ. (2004) Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors. Cancer Investigation, 22, 886–896.
19.
RyanQ.C., HeadleeD., AcharyaM., SparreboomA., TrepelJ.B., YeJ., FiggW.D., HwangK., ChungE.J., MurgoA., MelilloG., ElsayedY., MongaM., KalnitskiyM., ZwiebelJ., SausvilleE.A. (2005) Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. Journal of Clinical Oncology, 23, 3912–3922.
20.
ZhouN., MoradeiO., RaeppelS., LeitS., FrechetteS., GaudetteF., PaquinI., BernsteinN., BouchainG., VaisburgA., JinZ., GillespieJ., WangJ., FournelM., YanP.T., Trachy-BourgetM.C., KalitaA., LuA., RahilJ., MacLeodA.R., LiZ., BestermanJ.M., DelormeD. (2008) Discovery of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an orally active histone deacetylase inhibitor. Journal of Medicinal Chemistry, 51, 4072–4075.
21.
XieR., LiY., TangP., YuanQ. (2018) Design, synthesis and biological evaluation of novel 2-aminobenzamides containing dithiocarbamate moiety as histone deacetylase inhibitors and potent antitumor agents. European Journal of Medicinal Chemistry, 143, 320–333.
22.
ArrowsmithC.H., BountraC., FishP.V., LeeK., SchapiraM. (2012) Epigenetic protein families: a new frontier for drug discovery. Nature Reviews Drug Discovery, 11, 384–400.
23.
DangT.T.A., LeN.T.G., NguyenT.H., DinhT.C., NguyenH.T., NguyenT.T., HoangT.P., NguyenV.T., PhanV.K. (2017) Synthesis and cytotoxic evaluation of novel ester derivatives of betulin with AZT, d4T, and 3TC. Natural Product Communications, 12, 885–888.
24.
TranV.L., TranV.S., KamperdickC., AdamG.A. (2000) Synthesis of amino acid conjugates and further derivatives of 3α-hydroxylup-20(29)ene-23,28-dioic acid. Journal für praktische Chemie, 3, 42–63.
ŠarekJ., KlinotJ., DžubákP., KlinotováE., NoskováV., KřečekV., KořínkováG., ThomsonJ.O., Janošt'ákováA., WangS., ParsonsS., FischerP.M., ZhelevN.Z., HajdúchM. (2003) New lupane derived compounds with pro-apoptotic activity in cancer cells: Synthesis and structure-activity relationships. Journal of Medicinal Chemistry, 46, 5402–5415.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
