Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues
| Autor: | Steffen Hering, Miguel A. González-Cardenete, José M. Padrón, Ramón J. Zaragozá, María Auxiliadora Dea-Ayuela, Rachel Basset, Fatima Rivas, Marco Stadler |
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| Přispěvatelé: | Ministerio de Ciencia, Innovación y Universidades (España), Producción Científica UCH 2021, UCH. Departamento de Farmacia |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
Pharmacology Ketone Stereochemistry Carboxylic acid Farmacología Antiproliferative activity 01 natural sciences Biochemistry Microbiology Article Antimalarial activity HeLa chemistry.chemical_compound Diterpenoid Moiety 03.- Garantizar una vida saludable y promover el bienestar para todos y todas en todas las edades Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics Abietane chemistry.chemical_classification Malaria - Chemotherapy biology 010405 organic chemistry Chemistry lcsh:RM1-950 Sandarac biology.organism_classification GABAA receptor modulators Terpenoid Callitrisic acid 0104 chemical sciences Ferruginol 010404 medicinal & biomolecular chemistry lcsh:Therapeutics. Pharmacology Infectious Diseases Paludismo - Farmacoterapia |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname CEU Repositorio Institucional Fundación Universitaria San Pablo CEU (FUSPCEU) Antibiotics Volume 10 Issue 2 RiuNet. Repositorio Institucional de la Universitat Politécnica de Valéncia Antibiotics, Vol 10, Iss 184, p 184 (2021) |
| DOI: | 10.3390/antibiotics10020184 |
| Popis: | [EN] The abietane-type diterpenoids are significant bioactive compounds exhibiting a varied range of pharmacological properties. In this study, the first synthesis and biological investigation of the new abietane-diterpenoid (+)-4-epi-liquiditerpenoid acid (8a) together with several of its analogs are reported. The compounds were generated from the readily available methyl callitrisate (7), which was obtained from callitrisic acid present in Moroccan Sandarac resin. A biological evaluation was conducted to determine the effects of the different functional groups present in these molecules, providing basic structure-activity relationship (SAR) elements. In particular, the ferruginol and sugiol analogs compounds 10-16 were characterized by the presence of a phenol moiety, higher oxidization states at C-7 (ketone), and the hydroxyl, methyl ester or free carboxylic acid at C19. The biological profiling of these compounds was investigated against a panel of six human solid tumor cell lines (HBL-100, A549, HeLa, T-47D, SW1573 and WiDr), four parasitic Leishmania species (L. donovani, L. infantum, L. guyanensis and L. amazonensis) and two malaria strains (3D7 and K1). Furthermore, the capacity of the compounds to modulate gamma-aminobutyric acid type A (GABA(A)) receptors (alpha(1)beta(2)gamma(2s)) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted. This research was funded by Spanish National Research Council: 201680I008; Austrian Science Fund: FWF W 1232; American Lebanese Syrian Associated Charities. Santander Bank. Spanish Ministry of Science: PGC2018-094503-B-C22 and "The APC was funded by MDPI". |
| Databáze: | OpenAIRE |
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