2. Academic Validation
  3. Synthesis and antiproliferative activity of podocarpane and totarane derivatives

Synthesis and antiproliferative activity of podocarpane and totarane derivatives

  • Eur J Med Chem. 2018 Oct 5:158:863-873. doi: 10.1016/j.ejmech.2018.09.051.
Soumicha Mahdjour 1,  Juan J Guardia 2,  Fernando Rodríguez-Serrano 3,  José Manuel Garrido 4,  Isabel Blancas López-Barajas 5,  Nuria Mut-Salud 6,  Rachid Chahboun 2,  Enrique Alvarez-Manzaneda 7
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Faculty of Sciences, University of Granada, 18071, Granada, Spain; Laboratory Productions, Plant and Microbial Valuations (LP2VM), Department of Biotechnology, University of Sciences and Technology of Oran Mohamed Boudiaf, BP 1525, EL M'Naouer, Oran, Algeria.
  • 2 Department of Organic Chemistry, Faculty of Sciences, University of Granada, 18071, Granada, Spain.
  • 3 Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Armilla, Granada, 18100, Spain; Biosanitary Research Institute of Granada (ibs.Granada), Granada, 18012, Spain.
  • 4 Biosanitary Research Institute of Granada (ibs.Granada), Granada, 18012, Spain; Department of Surgery and Its Specialities, University of Granada, Granada, 18016, Spain.
  • 5 Biosanitary Research Institute of Granada (ibs.Granada), Granada, 18012, Spain; Oncology Unit, San Cecilio University Hospital, Granada, 18005, Spain.
  • 6 Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Armilla, Granada, 18100, Spain.
  • 7 Department of Organic Chemistry, Faculty of Sciences, University of Granada, 18071, Granada, Spain. Electronic address: eamr@ugr.es.
PMID: 30248657 DOI: 10.1016/j.ejmech.2018.09.051
Abstract

The synthesis of podocarpanes, including 12,19-dihydroxy-13-acetyl-8,11,13-podocarpatriene (23), isolated from Gaultheria yunnanensis and not previously synthesized, and totarane-type Terpenoids, starting from the natural labdane trans-communic acid (15), is described. Their antiproliferative activities against MCF-7, T-84 and A-549 human tumoural cell lines are studied. An antiproliferative effect was induced by compounds 23, 27 and 28, with IC50 < 10 μM in two (27) or three cell lines (23 and 28). No correlation with log P values was observed. The totarane o-quinone 27, and especially the catechol 28, which is readily oxidisable to compound 27, were the most active compounds, highlighting the functional groups present in C11 and C12. Compound 28 showed limited toxicity in normal peripheral blood mononuclear cells (78.5% cell viability versus non-treated control cultures at 10 μM), and appeared to exert an antiproliferative effect in A-549 cells (IC50 0.6 μM) through a mechanism that involves the induction of Apoptosis mediated by an increased Bax/Bcl-2 ratio. The results of the present study indicate that compound 28, at least, might be useful as an antitumoral agent. Further studies are required to elucidate the cellular and molecular elements involved in its effect, and the activity/toxicity in preclinical models.

Keywords

Cancer; Catechol; Podocarpane terpenes; Synthesis; Totarane terpenes; ortho-Quinone.

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