Mono-THF ring annonaceous acetogenins from Annona squamosa

Area of Science:

• Natural Product Chemistry
• Pharmacognosy
• Medicinal Chemistry

Background:

• Annona squamosa (Annonaceae) is a plant source of bioactive compounds.
• Annonaceous acetogenins are a class of natural products with diverse biological activities.
• The brine shrimp lethality test (BST) is a common bioassay for identifying cytotoxic compounds.

Purpose of the Study:

• To isolate and characterize new acetogenins from Annona squamosa bark.
• To evaluate the cytotoxic potential of isolated compounds against human tumor cell lines.

Main Methods:

• Phytochemical investigation of Annona squamosa bark extract guided by the brine shrimp lethality test (BST).
• Isolation and structural elucidation of new Annonaceous acetogenins using spectroscopic techniques.
• In vitro cytotoxicity assays against a panel of six human tumor cell lines.

Main Results:

• Isolation of three novel acetogenins: 4-deoxyannoreticuin, cis-4-deoxyannoreticuin, and (2,4-cis and trans)-squamoxinone.
• 4-deoxyannoreticuin and cis-4-deoxyannoreticuin feature an unusual oxygen functionality at the C-9 position and a hydroxylated mono-tetrahydrofuran (THF) ring.
• (2,4-cis and trans)-squamoxinone, a ketolactone mixture, showed promising selective cytotoxicity against the pancreatic cancer cell line (PACA-2).

Conclusions:

• The bark of Annona squamosa yields structurally unique acetogenins with cytotoxic properties.
• The newly identified acetogenins, particularly (2,4-cis and trans)-squamoxinone, warrant further investigation for their anticancer potential.
• This study expands the chemical diversity of Annonaceous acetogenins and highlights Annona squamosa as a source of novel bioactive compounds.