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Neplanocin A, a novel cyclopentenyl analog of adenosine, is a naturally occurring antibiotic which exhibits significant antitumor activity. In the present study we demonstrate that neplanocin A is also a potent inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase. Analysis of the apparent irreversible inactivation of AdoHcy hydrolase by neplanocin A indicates that the drug is a tight binding inhibitor, exhibiting a stoichiometry of one molecule of inhibitor to one molecule (tetramer) of enzyme. Also neplanocin A is a potent inhibitor of vaccinia virus (WR). The inhibition of virus multiplication by neplanocin A may be related to an inhibition of S-adenosylmethionine-dependent macromolecular methylation reactions which are essential to the production of new virus particles (e.g. viral messenger RNA). To decrease its adverse effects, we performed docking studies with different substitutes of the Neoplacin with GOLD software. Pharmacophore mapping and ludi interaction were calculated for strengthening the binding of ligand with S-adenosyl-L-homocysteine hydrolase.
Keywords: Neplanocin A, Modelling, S-adenosylhomocysteine, Docking studies