Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

New Water-Soluble Cationic Metalloporphyrins as Potential Anticancer Agents

Tetrapyrrolic compounds such as porphyrins are extensively studied and described in the literature as a perspective new class of chemotherapeutics (1) and effective photosensitizers for cancer treatment and diagnosis (2). In the present work, new water-soluble cationic porphyrin (meso-tetra(4-N-allylpyridyl)-porphine [TAll4PyP]) and its Zn, Ag, Co, Fe metallocomplexes were synthesized and evaluated the contribution of toxic influence of different metals being included in porphyrine ring on cancer cell culture (human chronic myeloid leukemia). The structures and purity of all synthesized porphyrins were determined and characterized by the methods of TLC, NMR, and electronic absorption spectroscopy. Anticancer testing data have suggested that the investigated metalloporphyrins may be arranged by their toxic influence in the following order: Ag-TAll4PyP>Co-TAll4PyP>Zn-TAll4PyP>Fe-TAll4PyP>>TAll4PyP. Two well-known chemotherapeutics Cis-Platinum and Cyclophosphanum were tested on the same cancer cell line for comparison with anticancer activity of synthesized compounds. Investigation of anticancer activity of Cis-platinum has shown that Ag-TAll4PyP is more effective than Cis-Platinum. All the synthesized metalloporphyrins have demonstrated much more anticancer activity than that of Cyclophosphanum. Investigation of phototoxicity of synthesized (metallo)porphyrins showed that free porphyrin and its Zn metallocomplex have significantly higher photo-influence, than Ag, Fe, Co metallocomplexes of TAll4PyP. Thus, (i) new water-soluble cationic porphyrin and its Zn, Ag, Co, Fe metallocomplexes were synthesized, (ii) the presence of the central metal atom in porphyrin ring is responsible for the cytotoxic action of porphyrins, and (iii) mechanism of cytotoxic influence of various metalloporphyrins includes not only the ways PDT does. Results suggest the high efficacy and perspectiveness of new metalloporphyrins; therefore, further studies will be preformed in understanding the mechanism and selectivity of metalloporphyrins? anticancer action.

This work was supported by the National Foundation of Science and Advanced Technologies (GRASP 29/06).

References and Footnotes
  1. (a) Ohse, T., Nagaoka, S., Arakawa, Y., Kawakami, H., Nakamura, K. J Inorg Biochem 85, 201-208, (2001). (b) Kasugai, N., Murase, T., Ohse, T., Nagaoka, S., Kawakami, H., Kubota, S. J Inorg Biochem 91, 349?355, (2002).
  2. (a) Berg, K., Selbo, P. K., Weyergang, A., Dietze, A., Prasmickaite, L., Bonsted, A., Engesaeter, B. O., Angell-Petersen, E., Warloe, T., Frandsen, N., Hogset, A. J Microscopy 218, Pt. 2, 133-147, (2005). (b) Dougherty, T. J., Gomer, C. J., Henderson, B. W., Jori, G., Kessel, D., Korbelik, M., Moan, J., Peng, Q. J Nat Canc Inst 90, 889-905, (1998). (c) Ghazaryan, R., Sahakyan, L., Tovmasyan, A. AM Patent N 1714, (2006).

Artak Tovmasyan1, *
Robert Ghazaryan1
Lida Sahakyan1
Gennadi Gasparyan2
Nelly Babayan2
Grigor Gyulkhandanyan3

1Yerevan State Medical University
2, Koryun str.
Yerevan, 0025 Armenia
2Yerevan State University
1, Alex Manoogian str.
Yerevan, 0025, Armenia
3Institute of Biotechnology
14, Gyurjyan str.
Yerevan, 0056 Armenia

*Phone: (37410)582821
Email: tovmartak@mail.ru