ABSTRACT
A method for the preparation of 3,5-bridged piperazin-2-ones from a tryptophan-proline-based diketopiperazine is described using diphosgene to induce the ring closure. Density functional theory calculations were conducted to study the mechanism of this C-C bond formation. Several derivatives of the thus obtained α-chloroamine were synthesized by substitution of the chlorine atom using a range of O-, N-, S-, and C-nucleophiles. This novel class of brevianamide F analogues possess interesting breast cancer resistance protein inhibitory activity.
Subject(s)
Breast Neoplasms/drug therapy , Diketopiperazines/chemistry , Indole Alkaloids/pharmacology , Neoplasm Proteins/antagonists & inhibitors , Breast Neoplasms/chemistry , Female , Humans , Indole Alkaloids/chemical synthesis , Indole Alkaloids/chemistry , Models, Molecular , Molecular Conformation , Quantum Theory , Stereoisomerism , Structure-Activity RelationshipABSTRACT
One part of chemical space that is endowed with interesting biological properties is the area of the chalcones. With this review, we provide a comprehensive overview of the numerous in vivo animal studies on the antineoplastic potential of both natural and synthetic members of this flavonoid subclass (covering: up to mid-2011). The thus far identified modes of action of these compounds are also discussed. We hope that this overview may stimulate deeper investigations into the biochemical mechanisms by which chalcones exert their antineoplastic action. As a result, in the foreseeable future, chalcones may prove suitable lead molecules or early drug candidates for the prevention or treatment of various neoplastic diseases.
