Ab initio study of fumagillin derivatives as potent anticancer compounds

Fumagillin is a complex biomolecule and used as antimicrobial for treatment of parasites in honey bees [1]. Furthermore, it can block blood vessel formation by binding to an enzyme named methionine aminopeptidase 2 (MetAP-2). Thus, it is investigated as an angiogenesis inhibitor in cancer treatment [2]. Fumagillin can covalently bind from reactive epoxide (connected to cyclohexane) and histidine-231 in the active site of MetAP-2 and the other epoxide ring on the side chain is dispensable [3,4]. It is suggested that the fumagillin epoxide ring can play an important role in potent angiogenic activity [5]. Unfortunately the covalent binding of fumagillin to MetAP-2 requires the oxygen protonation of the epoxied on the side chain [6]. Thus designing new derivatives is pioneer. Herein designing novel derivatives of fumagillin was performed and the suggested biomimics were optimized with ab initio method and 3-21g basis set.