Structural Analysis of Mogrol and its Glycosides as Inhibitors of Animal DNA Polymerase and Human Cancer Cell Growth
Mogroside I E1 (compound 3), a steroidal glycoside (i.e., mogroside) isolated from traditional Chinese medicinal plants (Momordica grosvenori) selectively inhibited the activities of animal DNA polymerases from mammals, fish and insects in vitro. The compound showed no effect on the activities of DNA polymerases from plants and procaryotes, and other DNA metabolic enzymes tested. Compound 3 also inhibited human cancer cell growth. Since parts of compound 3 such as mogrol (compound 1) and D-glucose (compound 2) did not influence the activities of any enzymes tested, the converted structure of compounds 1 and 2 might be important for DNA polymerase inhibition and the suppression of cancer cell growth. The other four mogrolal glycosides (i.e., compounds 4 - 7) did not influence the inhibition of DNA polymerase activity and human cancer cell proliferation. The relationship between the three-dimensional molecular structure of mogrol-based compounds and these inhibitory activities is discussed.
Keywords: Mogrol, mogroside, mogroside I E1, enzyme inhibitor, DNA polymerase, cytotoxicity, computer simulation
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