Coumarins structure-activity relationships

Kang SY, Lee KY, Sung SH, Park MJ, Kim YC, Coumarins isolated from Angelica gigas inhibit acetylcholinesterase Structure-activity relationships, f Nat Prod 64 683-685,2001. 

Raad, I., Terreux, R., Richomme, P., Matera, E.L., Dumontet, C., Raynaud, J., and Guilet, D. (2006) Structure-activity relationship of natural and synthetic coumarins inhibiting fhe multidrug transporter P-glycoprotein. Bioorganic and Medicinal Chemistry, 14 (20), 6979-6987. 

All of the coumarin derivatives (Fig. 31.5) are water-insoluble lactones. Structure-activity relationship requirements typically are based on substitution of the lactone ring, specifically in positions 3 and 4. Although coumarin is a neutral compound, the clinically available derivatives are weakly acidic because of the presence of a 4-hydroxy substitution. The acidity of the proton on the 4-hydroxy group allows formation of water-soluble sodium salts for commercial preparations. Furthermore, warfarin (and, possibly, ... 

Virtual screening for selective allosteric mGluRl antagonists and structure-activity relationship investigations for coumarine derivatives. ChemMedChem, 2, 1763—1773. 

Foti, M., Piattelli, M., Baratta, M.T., and Ruberto, G., Flavonoids, coumarins and cinnamic acids as antioxidants in a micellar system. Structure-activity relationship, J. Agric. Food Chem., 44, 497-501, 1990. 

Cheng J-F, Chen M, Wallace D, Tith S, Arrhenius T, Kashiwagi H, Ono Y, Ishikawa A, Sato H, Kozono T, Sato H, Nadzan AM (2004) Discovery and structure-activity relationship of coumarin derivatives as TNF-a inhibitors. Bioorg Med Chem Lett 14 2411-2415... 

Hoegberg, T. Vora, M. Drake, S. D. Mitscher,L. A. Chu, D. T. W. Structure-activity relationships among DNA-gyrase inhibitors. Synthesis and antimicrobial evaluation of chromones and coumarins related to oxolinic acid. Acta Chem. Scand., Ser B 1984, B38, 359-366. 

The third chapter, Quantitative Structure-Cytotoxicity Relationship of Bioactive Heterocycles by the Semi-empirical Molecular Orbital Method with the Concept of Absolute Hardness by Mariko Ishihara, Hiroshi Sakagami, Masami Kawase, and Noboru Motohashi, presents the relationship between the cytotoxicity (defined as 50% cytotoxic concentration) of heterocycles such as phenoxazine, 5-trifluoromethyloxazoles, O-heterocycles such as 3-formylchromone and coumarins, and vitamin K2 derivatives against some tumor cell lines and 15 chemical descriptors. The results suggest the importance of selecting the most appropriate descriptors for each cell type and compound. The review is of interest as it represents the relationship of the molecular structures with the cytotoxic activity of these heterocycles. 

The contradictory observations on the toxicity of coumarin stimulated our research into closely related coumarin derivatives in biochemical-pharmacological studies. Considering the limited information available in the various reviews on the biological properties of these compounds, the main emphasis in this paper will be placed on this aspect. It has been considered important to discuss the chemical structure-biological activity relationship of simple coumarins, coumarin anticoagulants, light sensitisers, aflatoxins, and related isocoumarin... 

Kawase, M. Sakagami, H. Hashimoto, K. Tani, S. Haner, H. Chatteijee, S. S. Structure-cytotoxic activity relationships of simple hydroxylated coumarins. Anticancer Res. 2003, 23, 3243-3246. Kawaii, S. Tomono, Y Ogawa, K. Suginra, M. Yano, M. Yoshizawa, Y. The antiproliferative effect of coumarins on several cancer cell lines. Anticancer Res. 2001, 21,917-923. 

It is difficult to make conclusions about the relationship between the structure of the coumarins and their action on complement mediated reactions. It might be concluded, however, that the methylated hydroxycoumarins 6 and 11 are the most potent inhibitors of AP and CP activities and deserve attention as a possible antiinflammatory agents. 

Investigations have been carried out to establish the structure-dose response relationship of coumarin raticides. The activities of the most important representatives of this group are tabulated (Table 3.11). Some synthetic coumarin derivatives have lately been added to these compounds, coumachlor (71) [484],cou-mafuryl (72) and coumatetralyl (73) [485]. 

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