Maiti Arup, Reddy P V Narasimha, Sturdy Megan, Marler Laura, Pegan Scott D, Mesecar Andrew D, Pezzuto John M, Cushman Mark
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, and the Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.
J Med Chem. 2009 Apr 9;52(7):1873-84. doi: 10.1021/jm801335z.
An efficient method has been developed to synthesize casimiroin (1), a component of the edible fruit of Casimiroa edulis, on a multigram scale in good overall yield. The route was versatile enough to provide an array of compound 1 analogues that were evaluated as QR2 and aromatase inhibitors. In addition, X-ray crystallography studies of QR2 in complex with compound 1 and one of its more potent analogues has provided insight into the mechanism of action of this new series of QR2 inhibitors. The initial biological investigations suggest that compound 1 and its analogues merit further investigation as potential chemopreventive or chemotherapeutic agents.
已开发出一种高效方法,可在多克规模上以良好的总收率合成可食果实卡西罗阿(Casimiroa edulis)中的成分卡西罗因(1)。该路线具有足够的通用性,能够提供一系列作为QR2和芳香酶抑制剂进行评估的化合物1类似物。此外,对与化合物1及其一种更有效的类似物形成复合物的QR2进行的X射线晶体学研究,为这一新系列QR2抑制剂的作用机制提供了深入了解。初步生物学研究表明,化合物1及其类似物作为潜在的化学预防或化学治疗剂值得进一步研究。