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

Autor: Steffen Hering, José M. Padrón, Fatima Rivas, Miguel A. González-Cardenete, Damir Hamulić, Rachel Bassett, M. Auxiliadora Dea-Ayuela, Marco Stadler, Marco A. Loza-Mejía
Přispěvatelé: Consejo Superior de Investigaciones Científicas (España), Ministerio de Economía y Competitividad (España), Austrian Science Fund, Banco Santander, American Lebanese Syrian Associated Charities, González-Cardenete, Miguel A. [0000-0002-8762-0426], Stadler, Marco [0000-0003-4489-6382], Padrón, José M. [0000-0002-7488-1774], Rivas, Fátima [0000-0003-3643-2035], UCH. Departamento de Farmacia, Producción Científica UCH 2019, González-Cardenete, Miguel A., Stadler, Marco, Padrón, José M., Rivas, Fátima
Rok vydání: 2019
Předmět:
Target
Antitumor-Promoting diterpenoids
Aromatic Abietane diterpenoids
Stereochemistry
Carboxylic acid
Pharmaceutical Science
Antineoplastic Agents
Nuclear receptors (Biochemistry)
Cells
01 natural sciences
Alcalis - Síntesis
Analytical Chemistry
Structure-Activity Relationship
chemistry.chemical_compound
Species Specificity
Stem bark
Cell Line
Tumor
Drug Discovery
Humans
Moiety
Structure–activity relationship
Hydroxymethyl
Cell Proliferation
Abietane
Leishmania
Pharmacology
chemistry.chemical_classification
Alkalies - Synthesis
Molecular Structure
Cytotoxic activity
010405 organic chemistry
Organic Chemistry
Semisynthesis
In vitro
0104 chemical sciences
Molecular Docking Simulation
Ferruginol
010404 medicinal & biomolecular chemistry
Células
Complementary and alternative medicine
chemistry
In-Vitro
Receptores nucleares (Bioquímica)
Molecular docking
Molecular Medicine
Diterpenes
Derivatives
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia
CEU Repositorio Institucional
Fundación Universitaria San Pablo CEU (FUSPCEU)
ISSN: 1520-6025
0163-3864
DOI: 10.1021/acs.jnatprod.8b00884
Popis: 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.
Financial support by the Spanish Government [Consejo Superior de Investigaciones Científicas (201680I008)] is gratefully acknowledged. M.S. thanks the support by the doctoral program “Molecular Drug Targets” (Austrian Science Fund FWF W 1232). F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC). M.A.D.-A. thanks the Santander Bank for the support for her project in consolidable groups of CEU-UCH.
Databáze: OpenAIRE
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