Indena Presents New Possibilities From Colchicine Derivatives for Cancer Treatment

Indena illustrates its findings at the Stony Brook Symposium

Stony Brook (NY), 29th September 2005 – “Colchicine and its analogues as potential anticancer drugs” was the topic of a lecture given by Ezio Bombardelli, President of the Indena Scientific Board, at the Stony Brook Symposium on “New Horizons in Organic Chemistry” held to celebrate the achievements of Dr Iwao Ojima.

Before an impressive gathering of academics and researchers from all over the world, Ezio Bombardelli pointed out that toxicity had always been a limit to the use of colchinoids. “Our experiments have demonstrated” he reported, “that dimeric derivatives of thiocolchicine, whose IDN 5404 is the lead, formulated with human serum albumin, show a consistent reduction in toxological effects and a corresponding increase in therapeutic efficacy”.

Moreover, extensive research on the action mechanism of these compounds highlighted that by modifying their molecular structure, these dimers can both interact with topoisomerasis I, an enzyme involved in DNA repetition, and inhibit tubulin polymerization, a known mechanism for this class of compounds. “Thanks to this double action mechanism, - Dr Bombardelli continued - dimers of thiocolchicine are extremely active against cellular lines of colon cancer resistant to treatment with cisplatinum.”

Colchicine is an alkaloid extracted from the seeds of Colchicum autumnale, a plant native to the Caucasian area; its use for the treatment of aching joints has been reported since the time of the Ancient Greeks. World demand for colchicine is still appreciably high today for the treatment of gout and it is sourced as a raw material for the manufacture of a drug widely used in Europe for the treatment of spasticity and muscular contractures. Colchicine is also known as an antimitotic agent and its citotoxic properties were discovered in 1889 by the Italian scientist Pernice.

Although Colchicine may well be considered to be the oldest citotoxic compound known to man, it still lacks any application in clinical anti cancer therapy. Indena has always believed in the potentiality of this class, and has never ceased to re-examine many natural and semi synthetic derivatives. Attention has been particularly focused on antineoplastic activities in tumoral forms resistant to cisplatinum and taxanes. Ezio Bombardelli concluded by expressing his pride in results which “ open new possibilities in the treatment of colon cancer and reaffirm Indena’s commitment to identifying new ways of fighting cancer”.

Indena is the world's leading company dedicated to the identification, development and production of active principles derived from plants, for use in the pharmaceutical, healthfood and cosmetics industries.

Indena, a privately owned Italian company, reported € 140 million in consolidated turnover in 2004, mostly generated abroad. The company, with around 700 employees, including 10% dedicated to full-time research, manages cultivation, manufacturing, and distribution operations in more than 40 countries throughout the world.
The key to Indena's success is its research, covering: the screening of medicinal plants for their pharmacological benefits; the identification of new active principles; and the development of extraction and purification systems at the cutting-edge of industrial application.

The phyto-chemical research is carried out in Indena's own Settala Research Center, near Milan. Indena also co-operates with the world's most prestigious universities and private research institutions in the biological assessment of safety and effectiveness up to clinical phase I.

Backed up by over 80 years of botanical experience, the Italian company has developed a plantation network, managed by experts, to supply its research and production centers with officinal plants, while at the same time ensuring bio-diversity and protecting the ecosystem balance from uncontrolled harvesting. Today more than 60% of the raw material used in the manufacturing process comes from cultivation.

Indena's decades-long global presence in the plant extraction industry is a guarantee of its in-depth knowledge and understanding of the business, the market and the legal framework. The Company's experts communicate and interact constantly with the major international regulatory authorities such as WHO, EMEA, and ESCOP, and work with all the main pharmacopoeias.

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