Cryptophycins were originally discovered in 1990 in cyanobacteria of the genus Nostoc.[1] Cryptophycins were patented as antifungal agents with an unknown mechanism of action and subsequently identified as microtubule inhibitors.[2] Closely related molecules were reported in the marine spongeDysidea arenaria, which were first given the name arenastatins.[3] However, since cyanobacteria are common symbionts of sponges, it has been suggested that bacteria may be the true origin in cases where sponge and bacterial metabolites closely resemble one another.[4] Nevertheless, study of the structure-activity relationships between the two subgroups of molecules led to improved understanding of their cytotoxic effects.[5]Шаблон:Rp
Mechanism of action
Cryptophycins are potent microtubule inhibitors, with a mechanism of action similar to that of vinca alkaloids.[2][6][7] Treatment of cells with cryptophycins depletes microtubules through interaction with tubulin, thereby preventing cell division.[8] Cryptophycins are capable of inducing apoptosis,[9] possibly through other mechanisms in addition to that mediated by microtubule inhibition.[10]
Clinical studies
Members of the cryptophycin family have been studied as anti-tumor agents. Cryptophycin-52, a synthetic analog of natural product cryptophycins also known as LY355703,[11] reached phase II clinical trials but was withdrawn due to side effects.[12]
Synthesis
Cryptophycins were first isolated from cyanobacteria but have subsequently been produced by chemical synthesis.[13][14] Chemoenzymatic syntheses have also been reported.[15][16]