ANNONACEOUS ACETOGENINS

ANNONACEOUS ACETOGENINS
The Annonaceae (custard-apple family), considering its large size (130 genera and 2300 species), is chemically one of the
least known of the tropical plant families.

กระดังงา (Cananga odorata)

ผลนอยหนา (Annona squamosa)

ทุเรียนเทศ (Annona muricata)

ANNONACEOUS ACETOGENINS
Chemically, these are C35-C38 compounds, apparently of polyketide origin, possessing one or two tetrahydrofuran
rings and a y-lactone (either saturated or unsaturated), usually involving a three-carbon chain attached to a long
aliphatic chain, and having long unbranched aliphatic regions that are variously hydroxylated, acetoxylated, or ketonized
ANNONACEOUS ACETOGENINS
The Annonaceous acetogenins are a series of C-35/C-37 natural products derived from C-32/C-34 fatty acids that are
combined with a 2-propanol unit. They are usually characterized by a long aliphatic chain bearing a terminal
methyl-substituted R,â-unsaturated γ-lactone ring (sometimes rearranged to a ketolactone), with one, two, or three
tetrahydrofuran (THF) rings located along the hydrocarbon chain and a number of oxygenated moieties (hydroxyls,
acetoxyls, ketones, epoxides) and/or double bonds being present

ketolactone
STRUCTURAL CLASSES
Three structural classes are currently evident when considering the number and arrangement of the tetrahydrofuran rings.

1. ADJACENT BIS-TETRAHYDROFURAN RING ACETOGENINS

2. MONOTETRAHYDROFURAN ANNONACEOUS ACETOGENINS

3. NONADJACENT BIS-TETRAHYDROFURAN ANNONACEOUS ACETOGENINS

4. NON-TETRAHYDROFURAN ANNONACEOUS ACETOGENINS

5. NONCLASSICAL ANNONACEOUS ACETOGENINS (THP and ring-hydroxylated THF compounds)

6. TRITETRAHYDROFURAN ANNONACEOUS ACETOGENINS

1. ADJACENT BIS-TETRAHYDROFURAN RING ACETOGENINS
l largest class of this compound type. Uvaricin is the prototype of compounds in this class. All of the reported
compounds of this class possess the same basic carbon skeleton
2. MONOTETRAHYDROFURAN ANNONACEOUS ACETOGENINS

Annonacin as the first Annonaceous acetogenin containing a single tetrahydrofuran ring. Since this report
several other monotetrahydrofuran acetogenins have been described.
3. NONADJACENT BIS-TETRAHYDROFURAN ANNONACEOUS ACETOGENINS

All structures described so far are 4-hydroxy derivatives. From the spectral data published, almunequine appears to be in this
structural subclass, although the compound is not fully characterized.
4. NON-TETRAHYDROFURAN ANNONACEOUS ACETOGENINS

5. NONCLASSICAL ANNONACEOUS ACETOGENINS

6. TRITETRAHYDROFURAN ANNONACEOUS ACETOGENINS

BIOGENESIS

- Annonaceous acetogenins are derivative from the polyketide pathway.

- THF , THP and epoxide rings are arised from isolated double bonds through epoxidation and
cyclization
- Acetogenins are derivative from lacceroic (c-32) and ghedoic (c-34) fatty acids after enzymatic
combination with a three-carbon unit.
- Plant in this family choose to biosynthesize more than 350 different acetogenins.
- all of them are either c-32 or c-34 fatty acid derivative
Epoxidation

Cyclization
BIOGENESIS
The discoveries of muridienins, proposed precursors of the mono-THF acetogenins

chatenaytrienins, proposed precursors of the bis-THF acetogenin

BIOGENESIS
Lacceroic acid (c-32)

Ghedoic acid (c-34)

MECHANISM OF ACTION
1. Annonaceous acetogenin can inhibit exogenous ubiquinone that it is a
noncompetitive inhibitor. (but this conclusion isn’t agree)
2. Annonaceous acetogenin and Rotenone can bind noncompetitively to
inhibit exogenous ubiquinone at complex I but they have different binding
sites on exogenous ubiquinone at complex I
BIOLOGICAL ACTIVITY

1. Antibacterial
2. Antimalarial
3. In vivo antitumor
4. Parasiticidal
5. Pesticidal
6. thwarting resistance in multidrug resistant tumor and in pesticide resistant
insect.