Synthesis and biological activity of a new benzothiazol derivative of curcumin

Recently much attention has been focused in the research of curcumin, a secondary metabolite isolated from Curcuma longa L. and from other species of Curcuma. Current investigation of curcumin is fastly increasing due to its biological activities (anti-inflammatory, [1] antioxidant, anti-HIV, [2] including cytotoxic effects on several cancer line cells [3, 4] and upon cystic fibrosis [5]). A benzothiazol derivative of curcumin was obtained by systematic structural modification of curcumin (Scheme) . We have described previously the synthesis of new heterocyclic derivatives of curcumin including the compound 4 [6]. The benzothiazol 4 was prepared by the reaction of 3 and 2-aminobenzenethiol. During the ring formation a part of the molecule of curcumin suffered fragmentation. The structure of 4 was assessed by spectroscopic methods (IR, 1D and 2D NMR, mass spectrometry), also the crystal structure was analyzed by X-ray crystallography. In our preliminary biological studies, compound 4 has shown important cytotoxic effect toward a nasopharyngeal carcinoma cell line KB (ED 50 =3.38µg/mL) as well as modification of the percentage of cells on cell cycle phases of the monocytic human cell line TPH1. Acknowledgements : CONACYT of México (37821-N and 40959-Q); DGAPA of UNAM (IN232202). References : 1. Ali, M., et al . (1995) , Ind. J. Chem. 34B: 884. 2. Artico, M., et al. (1998), J. Med. Chem., 41: 3948. 3. Huang, M.T., et al . (1992 ), ACS Symposium Series 507: 338. 4. Ishida, J. et al. (2002) , Biorg. Med. Chem. 10: 3481. 5. Egan, M. F. et al . (2004) , Science, 304: 600. 6. M. Concepción Lozada, et al ., (2004), Heterocycles 65: 49.