https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

The Annonaceous acetogenins are promising new antitumor and pesticidal agents that are found only in the plant family Annonaceae. Chemically, they are derivatives of long-chain fatty acids. Biologically, they exhibit their potent bioactivities through depletion of ATP levels via inhibiting complex I of mitochondria and inhibiting the NADH oxidase of plasma membranes of tumor cells. Thus, they thwart ATP-driven resistance mechanisms. This review presents the progress made in the chemistry, biology, and development of these compounds since December 1995.

Annonaceous Acetogenins: Recent Progress

The Department of Medicinal Chemistry and Molecular Pharmacology’s laboratory has adopted four “bench top” bioassays which do not require higher animals to screen and direct the fractionation of botanical extracts in drug discovery efforts. These are: 1. The brine shrimp lethality test (BST) (a general bioassay), 2. The inhibition of crown gall tumors on discs of potato tubers (an antitumor bioassay), 3. The inhibition of frond proliferation in duckweed (a bioassay for herbicides and plant growth stimulants), and 4. The yellow fever mosquito larvae lethality test (a bioassay for pesticides). The materials and procedures for those bioassays will be briefly described. The authors’ results in applying these simple methods in the discovery of Annonaceous acetogenins will be presented to illustrate their successful use. The BST is especially suggested as an inexpensive, simple, and rapid means of standardization of bioactivity in heterogeneous botanical products.

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The Use of Biological Assays to Evaluate Botanicals

Acetogenins from Annonaceae: recent progress in isolation, synthesis and mechanisms of action

In this study, 221 phytocompounds were evaluated for activity against anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) activities using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. Ten diterpenoids (1-10), two sesquiterpenoids (11 and 12), two triterpenoids (13 and 14), five lignoids (15-19), curcumin (20), and reference controls niclosamide (21) and valinomycin (22) were potent inhibitors at concentrations between 3.3 and 10 microM. The concentrations of the 22 compounds to inhibit 50% of Vero E6 cell proliferation (CC50) and viral replication (EC50) were measured. The selective index values (SI = CC50/EC50) of the most potent compounds 1, 5, 6, 8, 14, and 16 were 58, >510, 111, 193, 180, and >667, respectively. Betulinic acid (13) and savinin (16) were competitive inhibitors of SARS-CoV 3CL protease with Ki values = 8.2 +/- 0.7 and 9.1 +/- 2.4 microM, respectively. Our findings suggest that specific abietane-type diterpenoids and lignoids exhibit strong anti-SARS-CoV effects.

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Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus.

Recent advances in annonaceous acetogenins

Two new sesquiterpenes, 10 alpha-hydroxyamorphan-4-en-3-one (1) and 4 alpha-methylcadinane-4 alpha-methyl-1 alpha,2 alpha,10 alpha-triol (2), together with four known compounds, sesquiterpenes 10 alpha-hydroxycadinan-4-en-3-one (3) and alpha-cadinol (4), diterpene ferruginol and lignan helioxanthin, were isolated from the whole plant of Taiwania cryptomerioides under bioassay-guided fractionations. The structures of 1 and 2 were elucidated mainly by the NMR spectroscopic analyses. Bioactivities of the isolated compounds against brine shrimp, yellow fever mosquito larvae, and human tumor cells are reported; compound 4 was the most bioactive, showing selectivity for the human colon tumor cell line (HT-29).

Bioactive compounds from Taiwania cryptomerioides.

Mucocin: A New Annonaceous Acetogenin Bearing a Tetrahydropyran Ring

Bioactivity-guided fractionation of the latex of Euphorbia poisonii Pax. (Euphorbiaceae) led to the isolation and characterization of a new tigliane diterpene, 12-deoxyphorbol 13-(9,10-methylene)un...

Selectively Cytotoxic Diterpenes from Euphorbia poisonii

Activity-guided fractionation of the stem bark of Annona senegalensis gave four bioactive ent-kaurenoids (1-4). Compound 2 showed selective and significant cytotoxicity for MCF-7 (breast cancer) cells (ED50 1.0 microgram/mL), and 3 and 4 exhibited cytotoxic selectivity for PC-3 (prostate cancer) cells but with weaker potencies (ED50 17-18 micrograms/mL). The structure of the new compound, 3, was deduced from spectral evidence.

Guoen Shi

Papers

Recent advances in annonaceous acetogenins

Bioactive compounds from Taiwania cryptomerioides.

Mucocin: A New Annonaceous Acetogenin Bearing a Tetrahydropyran Ring

Selectively Cytotoxic Diterpenes from Euphorbia poisonii

Bioactive ent-Kaurene Diterpenoids from Annona senegalensis