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. 2021 Feb 12;10(2):184.
doi: 10.3390/antibiotics10020184.

Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues

Miguel A González-Cardenete  1 , Fatima Rivas  2 , Rachel Basset  2 , Marco Stadler  3 , Steffen Hering  3 , José M Padrón  4 , Ramón J Zaragozá  5 , María Auxiliadora Dea-Ayuela  6
Affiliations

Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues

Miguel A González-Cardenete et al. Antibiotics (Basel). .

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 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 (GABAA) receptors (α1β2γ2s) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted.

Keywords: GABAA receptor modulators; abietane; antimalarial activity; antiproliferative activity; callitrisic acid; diterpenoid.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Examples of bioactive abietane diterpenoids 1–7 and tested molecules 8a, and 9–16.
Scheme 1
Scheme 1
Synthesis of the tested compounds 8a and 9–16.
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References

    1. Newman D.J., Cragg G.M. Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. J. Nat. Prod. 2020;83:770–803. doi: 10.1021/acs.jnatprod.9b01285. - DOI - PubMed
    1. Singh N., Mishra B.B., Bajpai S., Singh R.K., Tiwari V.K. Natural product based leads to fight leishmaniasis. Bioorg. Med. Chem. 2014;22:18–45. doi: 10.1016/j.bmc.2013.11.048. - DOI - PubMed
    1. González M.A. Synthetic derivatives of aromatic abietane diterpenoids and their biological activities. Eur. J. Med. Chem. 2014;87:834–842. doi: 10.1016/j.ejmech.2014.10.023. - DOI - PubMed
    1. González M.A. Aromatic abietane diterpenoids: Their biological activity and synthesis. Nat. Prod. Rep. 2015;32:684–704. doi: 10.1039/C4NP00110A. - DOI - PubMed
    1. Ho S.-T., Tung Y.-T., Kuo Y.-H., Lin C.-C., Wu J.-H. Ferruginol Inhibits Non–Small Cell Lung Cancer Growth by Inducing Caspase-Associated Apoptosis. Integr. Cancer Ther. 2015;14:86–97. doi: 10.1177/1534735414555806. - DOI - PubMed