Coumarin and its 4- and 7- Substituted Derivatives as Retardants of Mitoses in Allium Root Promeristem

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Abstract
Coumarin and five derivatives (4-hydroxycoumarin, 7-hydroxycoumarin, 7-methylcoumarin, 7-methoxycoumarin, and 7-methoxy-4-methylcoumarin) were investigated for their potential as antimitotic agents. Coumarin and 4-hydroxycoumarin completely inhibited mitosis yet did not induce chromosomal aberrations in Allium sativum promeristem after 24 h treatment, and when postincubated in water did not exhibit mitotic recovery. 7-hydroxycoumarin also strongly inhibited cell proliferation (77% mitotic inhibition after 24 h). Sharp declines in mitotic activity of A. sativum promeristem were noted for 7-methylcoumarin, 7-methoxycoumarin, and 7-methoxy-4-methylcoumarin (83%, 90%, and 64% mitotic inhibition, respectively) in 24 h incubations. Chromosomal aberrations associated with 7-hydroxycoumarin treatment included shortening and thickening of chromosomes, postponed chromatid separation, anaphase and telophase bridges, and irregularly shaped nuclei. Disruption of normal chromosomal structure was also observed after exposure to the methyl- and/or methoxy-substituted derivatives, including formation of anaphase and telophase bridges, dispersed chromosomal structure, shorter and thicker chromosomes, and numerous large nucleoli. Aberrated fragmoplast formation was observed in 7-methoxycoumarin treated cells, generating binucleated cells. Differences in the antimitotic properties of the coumarins investigated suggest that these coumarin derivatives react with rapidly proliferating cells by different mechanisms as a result of their specific chemical substituents.