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]:230
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]
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synthetic analog of natural product cryptophycins also known as LY355703,[11] reached phase II clinical trials but was withdrawn due to side effects.[12]
Cryptophycins were first isolated from cyanobacteria but have subsequently been produced by chemical synthesis.[13][14] Chemoenzymatic syntheses have also been reported.[15][16]
Schwartz, Robert E.; Hirsch, Charles F.; Sesin, David F.; Flor, James E.; Chartrain, Michel; Fromtling, Robert E.; Harris, Guy H.; Salvatore, Michael J.; Liesch, Jerrold M.; Yudin, Katherine (April 1990). "Pharmaceuticals from cultured algae". Journal of Industrial Microbiology. 5 (2–3): 113–123. doi:10.1007/BF01573860. S2CID34480729.
Smith, CD; Zhang, X; Mooberry, SL; Patterson, GM; Moore, RE (15 July 1994). "Cryptophycin: a new antimicrotubule agent active against drug-resistant cells". Cancer Research. 54 (14): 3779–84. PMID7913408.
Piel, Jörn (2004-01-01). "Metabolites from symbiotic bacteriaThis review is dedicated to Professor Axel Zeeck on the occasion of his 65th birthday". Natural Product Reports. 21 (4): 519–38. doi:10.1039/b310175b. PMID15282634.
Cragg, edited by Gordon M.; Kingston, David G.I.; Newman, David J. (2012). Anticancer agents from natural products (2nded.). Boca Raton, FL: CRC Press. ISBN9781439813836.{{cite book}}: |first1= has generic name (help)
Trimurtulu, Golakoti; Ohtani, Ikuko; Patterson, Gregory M. L.; Moore, Richard E.; Corbett, Thomas H.; Valeriote, Frederick A.; Demchik, Lisa (June 1994). "Total Structures of Cryptophycins, Potent Antitumor Depsipeptides from the Blue-Green Alga Nostoc sp. Strain GSV 224". Journal of the American Chemical Society. 116 (11): 4729–4737. doi:10.1021/ja00090a020.
Field, Jessica J.; Kanakkanthara, Arun; Miller, John H. (September 2014). "Microtubule-targeting agents are clinically successful due to both mitotic and interphase impairment of microtubule function". Bioorganic & Medicinal Chemistry. 22 (18): 5050–5059. doi:10.1016/j.bmc.2014.02.035. PMID24650703.