Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues

• Published in: Antibiotics (Basel) Vol. 10; no. 2; p. 184
• Main Authors: González-Cardenete, Miguel A, Rivas, Fatima, Basset, Rachel, Stadler, Marco, Hering, Steffen, Padrón, José M, Zaragozá, Ramón J, Dea-Ayuela, María Auxiliadora
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-02-2021; MDPI
• Subjects: abietane; Acids; Analogs; antimalarial activity; antiproliferative activity; Apoptosis; Bioactive compounds; Biological effects; callitrisic acid; Carboxylic acids; Cytotoxicity; Diterpenes; diterpenoid; Functional groups; GABAA receptor modulators; Malaria; Melanoma; Molecular structure; Natural products; Parasites; Phenols; Skin cancer; Solid tumors; Tumor cell lines; Vector-borne diseases; γ-Aminobutyric acid; γ-Aminobutyric acid A receptors; diterpenoid; antimalarial activity; GABAA receptor modulators; callitrisic acid; abietane; antiproliferative activity
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics10020184

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
-
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
species (
,
,
and
) and two malaria strains (3D7 and K1). Furthermore, the capacity of the compounds to modulate gamma-aminobutyric acid type A (GABA
) receptors (α
β
γ
) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted.