2. Academic Validation
  3. Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies

Synthesis and Biological Studies of (+)-Liquiditerpenoic Acid A (Abietopinoic Acid) and Representative Analogues: SAR Studies

  • J Nat Prod. 2019 Apr 26;82(4):823-831. doi: 10.1021/acs.jnatprod.8b00884.
Damir Hamulić 1,  Marco Stadler 2,  Steffen Hering 2,  José M Padrón 3,  Rachel Bassett 4,  Fatima Rivas 4,  Marco A Loza-Mejía 5,  M Auxiliadora Dea-Ayuela 6,  Miguel A González-Cardenete 1
Affiliations

Affiliations

  • 1 Instituto de Tecnología Química (UPV-CSIC) , Universitat Politècnica de Valencia-Consejo Superior de Investigaciones Científicas , Avenida de los Naranjos s/n , 46022 Valencia , Spain.
  • 2 Department of Pharmacology and Toxicology , University of Vienna , Althanstrasse 14 , A-1090 Vienna , Austria.
  • 3 BioLab, Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN) , Universidad de La Laguna , C/Astrofísico Francisco Sanchez 2 , La Laguna 38200 , Tenerife , Spain.
  • 4 Department of Chemical Biology and Therapeutics , St. Jude Children's Research Hospital , Memphis , Tennessee 38105 , United States.
  • 5 Facultad de Ciencias Químicas , Universidad La Salle México , Avenue Benjamín Franklin 45 , Condesa , 06140 Ciudad de México , Mexico.
  • 6 Departamento de Farmacia , Universidad CEU Cardenal Herrera , Avenida Seminario s/n , 46113 Moncada (Valencia) , Spain.
PMID: 30840453 DOI: 10.1021/acs.jnatprod.8b00884
Abstract

The first semisynthesis and biological profiling of the new abietane diterpenoid (+)-liquiditerpenoic acid A (abietopinoic acid) (7) along with several analogues are reported. The compounds were obtained from readily available methyl dehydroabietate (8), which was derived from (-)-abietic acid (1). Biological comparison was conducted according to the different functional groups, leading to some basic structure-activity relationships (SAR). In particular, the ferruginol and sugiol analogues 7 and 10-16 were characterized by the presence of an acetylated phenolic moiety, an oxidized C-7 as a carbonyl, and a different functional group at C-18 (methoxycarbonyl, carboxylic acid, and hydroxymethyl). The biological properties of these compounds were investigated against a panel of six representative human tumor solid cells (A549, HBL-100, HeLa, SW1573, T-47D, and WiDr), five leukemia cellular models (NALM-06, KOPN-8, SUP-B15, UoCB1, and Bcr-Abl), and four Leishmania species ( L. infantum, L. donovani, L. amazonensis, and L. guyanensis). A molecular docking study pointed out some targets in these Leishmania species. In addition, the ability of the compounds to modulate GABAA receptors (α1β2γ2s) is also reported. The combined findings indicate that these abietane Diterpenoids offer a source of novel bioactive molecules with promising pharmacological properties from cheap chiral-pool building blocks.

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