Anticancer Activity and Molecular Mechanisms of Action of Makaluvamines and Analogues
The marine ecosystem presents an immensely rich chemical and biological resource for the discovery of new anticancer drugs. Recently, marine alkaloids, isolated from various aquatic flora and fauna, have been found to exhibit potent anticancer activities. These compounds range structurally from simple linear peptides to complex macrocyclic polyethers and are amenable to synthetic derivatization. Makaluvamines, a class of iminoquinone alkaloids isolated from marine sponges of the genera Zyzzya, have been reported to possess excellent in vitro and in vivo cytotoxicity against several cancer types. Until recently, these compounds have been thought to mainly act as DNA topoisomerase II inhibitors. A series of synthetic makaluvamine analogs have now been shown to inhibit cell proliferation and cell cycle progression, to induce apoptosis, and to modulate the expression of several genes such as MDM2, p21, and p53. The in vitro and in vivo results reported thus far provide a basis for future preclinical and clinical development of this class of compounds for cancer therapy.
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