Indian Journal of Biotechnology Vol 10, October 2011, pp 387-394 Synthesis, characterization and cytotoxicity of new Ho(III) and Er(III) complexes Irena Kostova 1 *, Petar Grigorov 1 , Stefan Balkansky 1 and Tsvetanka Stefanova 2 1 Department of Chemistry, Faculty of Pharmacy, Medical University, Sofia 1000, Bulgaria 2 Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria New complexes of coumarin-3-carboxylic acid (HCCA) with holmium [Ho(III)] and erbium [Er(III)] were synthesized and their structures and spectral properties were investigated by elemental analysis, IR, Raman and NMR measurements. According to the experimental data of the complexes, their formulae and geometries have been suggested. Vibrational frequencies, IR intensities and Raman activities as well as 1 H NMR chemical shifts of HCCA and its lanthanum [Ln(III)] complexes are presented. The comparative experimental spectral analyses of both the ligand and the Ln(III) complexes predicted the bidentate binding to Ho(III) and Er(III) through the deprotonated carboxylic oxygen and the carbonylic oxygen of the ligand. The cytotoxic/cytostatic properties of the ligand and the newly synthesized complexes of coumarin-3-carboxylic acid with Ho(III) and Er(III) were tested by MTT reduction assay against two mouse tumour cell lines, melanoma B16 and fibrosarcoma L929, as well as against normal mouse peritoneal macrophages. The proliferation inhibitory effect of the complexes compared to that of the ligand proved their cytotoxic/cytostatic properties against both the tumour cell lines. The complexes were less cytotoxic against normal mouse macrophages and modulated NO release by activated macrophages. The results are in accordance with our previously published data on the activity of lanthanide (III) complexes with coumarins. Keywords: Coumarins, cytotoxic/cytostatic activity; Er(III), FT-IR, FT-Raman, Ho(III) Introduction Coumarin derivatives possess a wide spectrum of biological activities 1-4 . Due to the potential applications in pharmaceutical industry, coumarins occupy an important position in natural and synthetic medicinal chemistry. Synthesis of coumarins and their derivatives has attracted considerable attention of organic and medicinal chemists for many years as a large number of natural products contain this heterocyclic nucleus 1-4 . Coumarins comprise a vast array of biologically active compounds ubiquitous in plants, many of which had been used in traditional medicine for thousands of years. Many coumarins and their derivatives exert anticoagulant, antitumour, antiviral, antiinflammatory and antioxidant effects, as well as antimicrobial and enzyme inhibition properties. A large number of structurally novel coumarin derivatives had shown substantial cytotoxic activity both in vitro and in vivo. The recognition of key structural features within coumarin family is crucial for the design and development of new analogues with improved activity and for the characterization of their mechanism of action and potential side effects. The different substituents in the coumarin nucleus strongly influence the biological activity of the resulting derivatives. Many coumarin derivatives in which -OH group is attached at 4-position are used widely as anticoagulants (warfarin, acenocoumarol, etc.) in the disorders related to excessive or undesirable clotting, such as, thrombophlebitis, pulmonary embolism, and certain cardiac conditions. They are also used as rodenticides due to their ability to cause fatal hemorrhaging. Hydroxylation at the 7-position is common in biosynthesis yielding such derivatives as umbelliferone (7-hydroxycoumarin), esculetin (6,7-dihydroxycoumarin), and scopoletin (7-hydroxy- 6-methoxycoumarin), which are the most widespread coumarins in nature. Synthetic 7-hydroxy coumarins are used to absorb ultraviolet rays in sunscreen cosmetics and are also used in the synthesis of drugs, especially, against cancer 5 . The ability of coumarins to bind metal ions represents an additional means of modulating their pharmacological responses. Nowadays, a lot of studies report complexes of coumarin derivatives with metals, which possess biological activity. Of many actions of coumarins ———————— *Author for correspondence: Tel. +359 29236569; Fax: +359 29879874 E-mail: irenakostova@yahoo.com