‘Plant-derived compounds in clinical trials’ (Saklani and Kutty, 2008)

Frances Watkins 29 November 2010

Market Share

• Global market valued at $18 billion in 2005 and estimated to be >$26 billion by 2011 • A review of 91 plant-derived compounds in clinical trials in Sep 2007 • 26 plant based drugs approved/launched between 2000-2006 including Artemotil, Galanthamine and Abraxane

Plant-based anticancer drugs

• 56 plant based anticancer drugs in clinical trials • Most promising analogues from Paclitaxel/Taxol, Camptothecin, Combrestatin, Podophyllotoxin and Vinca alkaloids

Structure of Taxol

Medicinal Plants

• 50% of prescription drugs in last 25 years have been derived from chemicals first identified in plants (Newman and Cragg, 2007) • Ever increasing need to develop new treatments for modern disease and more efficient medications for established health complaints • A growing interest in developing mixtures of natural products from traditional medicines (Harvey, 2008)

Health Applications

• Infectious and parasitic disease • Pain and neurological disease • Cardiovascular and metabolic disease • Inflammatory disease • Oncological disease

Traditional Use

•

Silybum marianum

(Asteraceae) used for liver and biliary tract disease – standardised extract in Phase II •

Lobelia inflata

- an emetic and respiratory stimulant; aid to cease smoking – Lobeline has been used for methamphetamine addiction and hyperactivity disorder (ADHD) • Xiao Chai Hu Tang (Minor Bupleurum Decoction) TCM herbal formulas used for hepatitis, liver cancer and nephritis

Galanthus nivalis

Plant Compounds

• The greatest contribution to medicine - the alkaloid group: quinine (isolated in 1820), codeine (1832), morphine (1806) and galanthamine (1950s) • Found in 15-30% of all flowering plants in the roots, rhizomes, leaves, bark, fruit or seeds • >40 alkaloids found in

Vinca major

Other Metabolites

• Catechins found in green tea, grapes, black tea, chocolate and wine • Many lignans i.e. flaxseed are converted by intestinal bacteria and become active metabolites which are then readily absorbed • Essential oils

Linum usitatissimum

Hoodia gordonii

Ethical Issues

• Plants facing threat through excessive harvesting: environment

Hoodia

species, Yew, Echinacea and Magnolia • Impact on local communities and • Generate sustainable cash crops for biomass – 2 x 10 8 Kg = 7.5 10 6 bushels

Future Perspectives

• Encouraging number of plant-based drugs in clinical trials although a 30% drop compared to pre 2000 (Harvey, 2008) • Modern techniques combined with traditional knowledge will offer a quicker route to drug discovery • Pharmaceutical industry recognising traditional medicinal systems are valuable leads to drug discovery (Verpoorte, 2009)

Thank you

• Any questions?

References

Harvey, A. (2008) ‘Natural products in drug discovery’.

Drug Discovery Today.

13, (19/20), pp.894-901.

Newman, DJ and Cragg , GM (2007) ‘Natural products as sources for new drugs over the last 25 years’.

Journal Natural Products

. 70, pp.461-477.

Saklani, A. and Kutty , S.K. (2008) ‘Plant-derived compounds in clinical trials’.

Drug Discovery Today

. 13, (3/4), pp.161-171.

Verpoorte , R. (2009) ‘A systems view on the future of medicine: Inspiration from Chinese medicine?’.

Journal of Ethnopharmacology.

121, pp.479-481.