Pharmacognosy: Shikimic Acid and Coumarins

Pharmacognosy and Phytochemistry (Coumarins/furanocoumarins/chromones)

• Shikimic acid is isolated from plants of Illicium species (Japanese "shikimi," Japanese star anise)
• The shikimic acid pathway is important for aromatic compounds
• It's a precursor of aromatic amino acids (Phe, Tyr, Try) biosynthesis in bacteria, fungi, and higher plants
• It's a building block for other compounds: alkaloids, coumarins, phenyl propanes, and volatile oils
• It's a starting point for tannins in all plants
• It provides protection of plants against microorganisms
• Oseltamivir phosphate (Tamiflu) is an orally active neuraminidase inhibitor, developed for treating and preventing influenza viruses A and B
• The starting material for the synthesis of oseltamivir is (-)-shikimic acid
• Shikimic acid is currently in demand as the raw material for the synthesis of oseltamivir (Tamiflu), for defense against avian influenza (bird flu)
• Illicium verum (star anise) contains large amounts of shikimic acid
• The drug manufacturer Roche currently relies on both extraction and fermentation to obtain shikimic acid

Coumarins

• Coumarin is a derivative of Benzo-α-pyrone
• It has a vanilla-like flavor
• It's an oxygen heterocycle
• Coumarin can be free or combined with glucose (coumarin glycoside)
• Coumarins are organic solvents-soluble
• Derivatives differ in benzene ring substitutions (OH, OCH₃, CH₃)
• Coumarins are common in Apiaceae, Fabaceae, and Rutaceae families
• Umbelliferone: R₁ = H, R₂ = OH
• Aesculetin: R₁ = R₂ = OH
• Scopoletin: R₁ = OCH₂, R₂ = OH
• Coumarins are hepatotoxic in high doses
• Coumarin and several derivatives have various therapeutic and pharmacological potentials.

Furanocoumarins (Photosensitizers)

• Often known as psoralens
• Plants containing psoralens are used internally and externally to promote skin pigmentation and suntanning
• Psoralen absorbs near UV light and stimulates melanin pigment formation
• Furan ring is derived from isopentyl pyrophosphate (mevalonic acid pathway)

Aflatoxins

• Aflatoxins are mycotoxins produced by the fungus Aspergilus
• Aflatoxins are potent hepatotoxins and carcinogens in the liver
• All aflatoxins contain a coumarin ring and an unsaturated lactone moiety

Bleeding

• Dicoumarol is present in sweet clover ( Melilotus officinalis)
• Dicoumarol interferes with the effects of vitamin K in blood coagulation.
• The blood loses its ability to clot, and minor injuries can lead to severe internal bleeding

Medical Value of Coumarins / Furanocoumarins

• Aesculin/Aescin from Aesculus hippocastanum reduces inflammation, and is used as an anti-inflammatory agent, and also for treating cutaneous capillary fragility
• Psoralens and derivatives used in PUVA photochemotherapy for vitiligo and psoriasis repigmentation.
• Methoxsalen (also known as xanthotoxin), commonly found in the fruits of Ammi majus is used for skin repigmentation.

Grapefruits

• Grapefruit juice inhibits CYP3A4-mediated drug metabolism
• Major furanocoumarins in grapefruits include bergamottin and 6',7'-dihydroxybergamottin

Other Details

• Warfarin, a coumarin derivative, is used as an anticoagulant
• Warfarin's discovery was linked to an outbreak of hemorrhaging in cattle consuming moldy sweet clover
• The 14th Dalai Lama's quote on happiness

Ammi visnaga

• Ammi visnaga contains furochromones, used traditionally as an antispasmodic and for angina pectoris treatment
• Khellin, extracted from Ammi visnaga, is a coronary vasodilator and spasmolytic agent
• Khellin and its analogs (e.g., amiodarone, cromolyn sodium) are also used in current medical practice