NUSANTARA BIOSCIENCE ISSN: 2087-3948 (print) Vol. 2, No. 2, Pp. 90-96 ISSN: 2087-3956 (electronic) July 2010 DOI: 10.13057/nusbiosci/n020207 Review: Colchicine, current advances and future prospects RAVINDRA ADE  , MAHENDRA KUMAR RAI Department of Biotechnology, SGB Amravati University, Amravati 444602, Maharashtra, India. Tel: +91-721-2662207/8, Extension-267. Fax: +91 721 2660949, 2662135. email: pmkrai@hotmail.com Manuscript received: 22 May 2010. Revision Accepted: 22 July 2010. Abstract. Ade R, Rai MK. 2010. Colchicine, current advances, and future prospects. Nusantara Bioscience 2: 90-96. Colchicine is a toxic natural compound and secondary metabolite commonly produced by plants like Colchicum autumnale and Gloriosa superba. It is originally used to treat rheumatic complaints, especially gout, and still finds its uses for these purposes today despite dosing issues concerning its toxicity. It is also prescribed for its cathartic and emetic effects. Initially, oral colchicine has not been approved as a drug by U.S. Food and Drug Administration (FDA). But now FDA approved colchicine as a drug for some disorders. Colchicine's present medicinal use is in the treatment of gout and familial Mediterranean fever. It is also being investigated for its use as an anticancer drug. In neurons, axoplasmic transport is disrupted by colchicine. Due to all the pharmacological application of colchicine, there is an urgent need to enhance the properties and increase the production of colchicine with the help of in vitro technologies. The present review is mainly focused on the chemistry of colchicine, its medicinal uses, and toxicity. Key words: colchicine, photoisomerization, colchicinamide, toxicity, polyploidy Abstrak. Ade R, Rai MK. 2010. Kolkisin, kelebihannya pada saat ini dan prospeknya di masa depan. Nusantara Bioscience 2: 90-96. Kolkisin adalah senyawa alami beracun dan metabolit sekunder yang umumnya dihasilkan oleh tanaman seperti Colchicum autumnale dan Gloriosa superba. Senyawa ini pada awalnya digunakan untuk mengobati keluhan rematik, terutama asam urat, dan tetap digunakan hingga kini, meskipun terdapat perdebatan mengenai dosis toksisitasnya. Senyawa ini juga diresepkan untuk efek katarsis dan emetik. Semula pemberian kolkisin secara oral sebagai obat belum disetujui oleh Badan Pengawas Obat dan Makanan Amerika Serikat (FDA), tetapi sekarang FDA menyetujui kolkisin sebagai obat untuk beberapa gangguan. Kolkisin digunakan dalam pengobatan asam urat dan demam mediterania familial. Senyawa ini juga sedang diselidiki kegunaannya sebagai obat antikanker, karena dalam neuron, transportasi akoplasma dapat dipengaruhi oleh kolkisin. Mengingat adanya aplikasi farmakologi kolkisin, maka perlu adanya upaya untuk memperbaiki sifat dan meningkatkan produksi kolkisin dengan bantuan teknologi in vitro. Telaah ini terutama difokuskan pada kimia kolkisin, serta penggunaannya sebagai obat dan toksisitasnya. Key words: kolkisin, fotoisomerisasi, colchicinamide, toksisitas, poliploidi. INTRODUCTION Colchicine is a traditional drug for gout (Wendelbo and Stuart 1985), and has been in use for treating acute gout dates back to 1810. It is obtained from corms of Gloriosa superba and also from Colchicum autumnale (Family Liliaceae). Since the approval of colchicine as drug for gout in 2009 by the Food and Drug Administration (FDA, USA) there has been revival of interest in colchicine research and applications (Schlesinger 2010). Colchicine is an extremely poisonous alkaloid, originally extracted from Colchicum autumnale (autumn crocus, meadow saffron) medicinal plants. It is used to treat rheumatic complaints. Colchicine was first isolated in 1820 by the two French chemists Pelletier and Caventon and extract of Colchicum plant was first described as a treatment for gout in De Materia Medica of Padanius Dioscorides. It was later identified as a tri-cyclic alkaloid and its pain relieving and anti-inflammatory effects for gout were linked to its binding with the protein tubulin. The molecular formula of colchicine is C22H25NO6 and its chemical name is N-[ (7S)- 5, 6, 7, 9-tetrahydro-1, 2, 3, 10-tetramethoxy-9- oxobenzo[a]heptalen-7-yl) acetamide]. The term ‘colchicine’ is originated from area known as “Colchis” near black sea. C. autumnale grows wild in Europe and Africa while Gloriosa is distributed in Africa and Asia including foothills of Himalayas, Burma, Indonesia, Malaya, etc. Thomson was the first who proposed the early idea of action of colchicine in gout treatment. Gout and uric acid metabolism is same way linked and colchicine might act on this. Gout is caused by deposition of micro-crystals of uric acid in joints and may be due to defective regulatory mechanism for endogenous purine synthesis but conflicting results for the action of colchicine on synthesis and extraction of urates have been recorded. The colchicine interrupts the cycle of new deposition, which appears to be essential for the maintenance of acute gout. The frequent side effect has been recorded, but colchicine remains the ideal drug for acute gout. Modification of the side chain of rings does not eliminate anti-gout activity as long as the configuration of C-ring confirms to that of colchicine. It suppresses cell