Background: Curcumin, chemically difeluroyl methane is a yellow polyphenol isolated from the rhizomes of perennial herb Curcuma longa. It has been shown highly cytotoxic towards various cancer cell lines but its water insolubility and instability make its bioavailability exceedingly low. Conjugation of curcumin with another drug increases the steric hindrance around the molecule and stabilizes it against chemical and enzymatic degradation. Metformin, chemically N, N’-dimethyl biguanide has been reported to exhibit anticancer potential by activating adenosine monophosphate activated protein kinase (AMPK) pathway. Methods: In the present work, novel curcumin-metformin conjugate was synthesised and evaluated for in vitro cytotoxic activity. It was prepared through a covalent bond between the phenolic hydroxyl group of curcumin and amino group of metformin using the linker succinic anhydride and by employing carbodiimide coupling agent dicylohexyl carbodiimide (DCC) in the presence of N-hydroxy succinimide (NHS). It was then characterized using IR, 1HNMR and mass spectroscopy analysis. The stability of the synthesized conjugate was studied in acidic and basic pH conditions by UV spectroscopic method. In vitro anticancer potential of the synthesised conjugate was studied by MTT assay. Results: Curcumin-metformin conjugate exhibited enhanced stability as compared to curcumin. It was found to significantly increase the cytotoxicity against MCF-7 and PA-1 cells as compared to the free drugs. Conclusion: It can be concluded that the synthesized conjugate has better stability in the gastrointestinal tract than curcumin and has the potential for optimizing anticancer therapy.
Key words: Conjugation, Curcumin, Drug-drug conjugate, Metformin, MTT assay.