Deoxybostrycin ( 1) is an anthraquinone compound derived from the marine mangrove fungus Nigrospora sp. No. 1403 and has potential to be a lead for new drugs because of its various biological properties. A series of new derivatives ( 2– 22) of deoxybostrycin were synthesized. The in vitro cytotoxicity of all the new compounds was tested against MDA-MB-435, HepG2 and HCT-116 cancer cell lines. Most of the compounds exhibit strong cytotoxicity with IC 50 values ranging from 0.62 to 10 μM. Compounds 19, 21 display comparable cytotoxicity against MDA-MB-435 to epirubicin, the positive control. The primary screening results indicate that the deoxybostrycin derivatives might be a valuable source of new potent anticancer drug candidates.
References
[1]
Heron, M. Deaths: Leading causes for 2005. Natl. Vital Stat. Rep. 2009, 58, 1–97.
[2]
Heron, M. Deaths: Leading causes for 2004. Natl. Vital Stat. Rep. 2007, 56, 1–96.
[3]
David, V.; Jaime, R.A.; Cristina, T.; Pedro, C.B.; Jaime, V.A. Studies on quinones. Part 46. Synthesis and in vitro antitumor evaluation of aminopyrimidoisoquinolinequinones. Eur. J. Med. Chem. 2010, 45, 5234–5242, doi:10.1016/j.ejmech.2010.08.040.
[4]
Thomas, E. Cancer therapy with natural products and medicinal plants. Planta Med. 2010, 76, 1035–1036, doi:10.1055/s-0030-1250062.
[5]
Wang, L.; Li, D.; Xu, S.; Cai, H.; Yao, H.; Zhang, Y.; Jiang, J.; Xu, J. The conversion of oridonin to spirolactone-type or enmein-type diterpenoid, synthesis and biological evaluation of ent-6,7-seco-oridonin derivatives as novel potential anticancer agents. Eur. J. Med. Chem. 2012, 52, 242–250, doi:10.1016/j.ejmech.2012.03.024.
[6]
Schwartsmann, G.; Da Rocha, A.B.; Mattei, J.; Lopes, R. Marine-derived anticancer agents in clinical trials. Expert. Opin. Inv. Drug 2003, 12, 1367–1383.
[7]
D’Incalci, M.; Simone, M.; Tavecchio, M.; Damia, G.; Garbi, A.; Erba, E. New drugs from the sea. J. Chemother. 2004, 16, 86–89.
[8]
O’Hanlon, L.H. Scientists are searching the seas for cancer drugs. J. Natl. Cancer Inst. 2006, 98, 662–663, doi:10.1093/jnci/djj218.
[9]
Banerjee, S.; Wang, Z.; Mohammad, M.; Sarkar, F.H.; Mohammad, R.M. Efficacy of selected natural products as therapeutic agents against cancer. J. Nat. Prod. 2008, 71, 492–496, doi:10.1021/np0705716.
[10]
Xia, X.K.; Li, Q.; Li, J.; Shao, C.L.; Zhang, J.Y.; Zhang, Y.G.; Liu, X.; Lin, Y.C.; Liu, C.H.; She, Z.G. Two new derivatives of griseofulvin from the mangrove endophytic fungus Nigrospora sp. (Strain No. 1403) from Kandelia candel (L.) Druce. Planta Med. 2011, 77, 1735–1738, doi:10.1055/s-0030-1271040.
[11]
Charudattan, R.; Rao, K.V. Bostrycin and 4-deoxybostrycin: Two nonspecific phytotoxins produced by Alternaria eichhorniae. Appl. Environ. Microbiol. 1982, 43, 846–849.
[12]
Sommart, U.; Rukachaisirikul, V.; Sukpondma, Y.; Phongpaichit, S.; Sakayaroj, J.; Kirtikara, K. Hydronaphthalenones and a dihydroramulosin from the endophytic fungus PSU-N24. Chem. Pharm. Bull. 2008, 56, 1687–1690, doi:10.1248/cpb.56.1687.
[13]
Ge, H.M.; Song, Y.C.; Shan, C.Y.; Ye, Y.H.; Tan, R.X. New and cytotoxic anthraquinones from Pleospora sp. IFB-E006, an endophytic fungus in Imperata cylindrical. Planta Med. 2005, 71, 1063–1065, doi:10.1055/s-2005-864190.
[14]
Nota, T.; Take, T.; Watanabe, T.; Abe, J. The structure of bostrycin. Tetrahedron 1970, 26, 1339–1346, doi:10.1016/S0040-4020(01)93004-2.
[15]
Chen, H.; Zhong, L.L.; Long, Y.H.; Li, J.; Wu, J.H.; Liu, L.; Chen, S.P.; Lin, Y.C.; Li, M.F.; Zhu, X.; She, Z.G. Studies on the synthesis of derivatives of marine-derived bostrycin and their structure-activity relationship against tumor cells. Mar. Drugs 2012, 10, 932–952, doi:10.3390/md10040932.
[16]
Miko, M.; Drobnica, L.; Chance, B. Inhibition of energy metabolism in Ehrlich ascites cells treated with dactylarin in vitro. Cancer Res. 1979, 39, 4242–4251.
[17]
Haraguchi, H.; Abo, T.; Fukuda, A.; Okamura, N.; Yagi, A. Mode of phytotoxic action of Altersolanols. Phytochemistry 1996, 431, 989–992.
[18]
Xie, G.E.; Zhu, X.; Li, Q.; Gu, M.H.; He, Z.J.; Wu, J.H.; Li, J.; Lin, Y.C.; Li, M.F.; She, Z.G.; et al. SZ-685C, a marine anthraquinone, is a potent inducer of apoptosis with anticancer activity by suppression of the Akt/FOXO pathway. Br. J. Pharmacol. 2010, 159, 689–697, doi:10.1111/j.1476-5381.2009.00577.x.
