Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2021 Mar 6

PMID 33673350

Citations 2

Authors

Miguel A Gonzalez-Cardenete

Fatima Rivas

Rachel Basset

Marco Stadler

Steffen Hering

Jose M Padron

Ramon J Zaragoza

Maria Auxiliadora Dea-Ayuela

Affiliations

Soon will be listed here.

Abstract

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 (αβγ) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted.

Citing Articles

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids.

Gonzalez-Cardenete M, Hamulic D, Miquel-Leal F, Gonzalez-Zapata N, Jimenez-Jarava O, Brand Y J Nat Prod. 2022; 85(8):2044-2051.

PMID: 35969814 PMC: 9425435. DOI: 10.1021/acs.jnatprod.2c00464.

Abietane Diterpenoids from the Hairy Roots of .

Kentsop R, Iobbi V, Donadio G, Ruffoni B, De Tommasi N, Bisio A Molecules. 2021; 26(17).

PMID: 34500582 PMC: 8434070. DOI: 10.3390/molecules26175144.

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