Seven new formamido-diterpenes, cavernenes A–D ( 1– 4), kalihinenes E and F ( 5– 6), and kalihipyran C ( 7), together with five known compounds ( 8– 12), were isolated from the South China Sea sponge Acanthella cavernosa. Structures were established using IR, HRESIMS, 1D and 2D NMR, and single X-ray diffraction techniques. The isolated compounds were assessed for their cytotoxicity against a small panel of human cancer cell lines (HCT-116, A549, HeLa, QGY-7701, and MDA-MB-231) with IC 50 values in the range of 6–18 μM. In addition, compound 9 showed weak antifungal activity against Trichophyton rubrum and Microsporum gypseum with MIC values of 8 and 32 μg/mL, respectively, compound 10 displayed weak antifungal activity against fungi Candida albicans, C ryptococcus neoformans, T. rubrum, and M. gypseum with MIC values of 8, 8, 4, and 8 μg/mL, respectively.
Trimurtulu, G.; Faulkner, D.J. Six new ditepene isonitriles from the sponge Acanthella cavernosa. J. Nat. Prod. 1994, 57, 501–506, doi:10.1021/np50106a009.
[3]
Clark, R.J.; Stapleton, B.L.; Garson, M.J. New isocyano and isothiocyanato terpene metabolites from the topical marine sponge Acanthella cavernosa. Tetrahedron 2000, 56, 3071–3076, doi:10.1016/S0040-4020(00)00226-X.
[4]
Angerhofer, C.K.; Pezzuto, J.M. Antimalarial activity of sesquiterpenes from the marine sponge Acanthella klethra. J. Nat. Prod. 1992, 55, 1787–1789, doi:10.1021/np50090a014.
[5]
Jumaryatno, P.; Stapleton, B.L.; Hooper, J.N.A.; Brecknell, D.J.; Blanchfield, J.T.; Garson, M.J. A comparison of sesquiterpene scaffolds across different populations of the tropical marine sponge Acanthella cavernosa. J. Nat. Prod. 2007, 70, 1725–1730, doi:10.1021/np070156d. 17953446
[6]
Rodriguez, J.; Nieto, R.M.; Huter, L.M.; Diaz, M.C.; Crews, P. Variation among known kalihinol and new kalihinene diterpenes from the sponge Acanthella cavernosa. Tetrahedron 1994, 50, 11079–11090, doi:10.1016/S0040-4020(01)89411-4.
[7]
Sun, J.Z.; Chen, K.S.; Yao, L.G.; Liu, H.L.; Guo, Y.W. A new kalihinol diterpene from the hainan sponge Acanthella sp. Arch. Pharm. Res. 2009, 32, 1581–1584, doi:10.1007/s12272-009-2110-4. 20091271
[8]
Fusetani, N.; Yasumura, E.; Kawai, H.; Natori, T.; Binnen, L.; Clardy, J. Kalihinene and isokalihinol B, cytotoxic diterpene isonitriles from the marine sponge Acanthella klethra. Tetrahedron Lett. 1990, 31, 3559–3602, doi:10.1016/S0040-4039(00)94442-3.
[9]
Omar, S.; Albert, C.; Fanni, T.; Crews, P. Polyfunctional diterpene isonitriles from marine sponge Acanthella cavernosa. J. Org. Chem. 1988, 53, 5971–5972, doi:10.1021/jo00260a034.
[10]
Alvi, K.A.; Tenenbaum, L.; Crews, P. Anthelmintic polyfunctional nitrogen-containing terpenoids from marine sponges. J. Nat. Prod. 1991, 54, 71–78, doi:10.1021/np50073a002. 2045823
[11]
Miyaoka, H.; Shimomura, M.; Kimura, H.; Yamada, Y. Antimalarial activity of kalihinol A and new relative diterpenoids from the Okinawan sponge, Acanthella sp. Tetrahedron 1998, 54, 13467–13474, doi:10.1016/S0040-4020(98)00818-7.
[12]
Bugni, T.S.; Singh, M.P.; Chen, L.; Arias, D.A.; Harper, M.K.; Greenstein, M.; Maiese, W.M.; Concepcion, G.P.; Mangalindan, G.C.; Ireland, C.M. Kalihinols from two Acanthella cavernosa sponges: Inhibitors of bacterial folate biosynthesis. Tetrahedron 2004, 60, 6981–6988, doi:10.1016/j.tet.2003.08.082.
[13]
Chang, C.W.J.; Patra, A.; Roll, D.M.; Scheuer, P.J. Kalihinol-A, a highly functionalized diisocyano diterpenoid antibiotic from a sponge. J. Am. Chem. Soc. 1984, 106, 4644–4646, doi:10.1021/ja00328a073.
[14]
Patra, A.; Chang, C.W.J.; Scheuer, P.A.; Van Dayne, D.G.; Matsumoto, G.K.; Clardy, J. An unprecedented triisocyano diterpenoid antibiotic from a sponge. J. Am. Chem. Soc. 1984, 106, 7981–7983, doi:10.1021/ja00337a061.
[15]
Okino, T.; Yoshimura, E.; Hirota, H.; Fusetani, N. Antifouling kalihinenes from the marine sponge Acanthella cavernosa. Tedrahedron Lett. 1995, 36, 8637–8640, doi:10.1016/0040-4039(95)01861-B.
[16]
Okino, T.; Yoshimura, E.; Hirota, H.; Fusetani, N. New antifouling kalihipyrans from the marine sponge Acanthella cavernosa. J. Nat. Prod. 1996, 59, 1081–1083, doi:10.1021/np960496r.
[17]
Hirota, H.; Tomono, Y.; Fusetani, N. Terpenoids with antifouing activity against Barnacle larvae from the marine sponge Acanthella cavernosa. Tetrahedron 1996, 52, 2359–2368, doi:10.1016/0040-4020(95)01079-3.
[18]
Xu, Y.; Li, N.; Jiao, W.H.; Wang, R.P.; Peng, Y.; Qi, S.H.; Song, S.J.; Chen, W.S.; Lin, H.W. Antifouling and cytotoxic constituents from the South China Sea sponge Acanthella cavernosa. Tetrahedron 2012, 6, 2876–2883.
[19]
Garson, M.J.; Simpson, J.S. Marine isocyanides and related natural products—Structure, biosynthesis and ecology. Nat. Prod. Rep. 2004, 21, 164–179, doi:10.1039/b302359c. 15039841
[20]
Dorman, D.E.; Roberts, J.D. Nuclear magnetic resonance spectroscopy. Carbon-13 spectra of some pentose and hexose aldopyranoses. J. Am. Chem. Soc. 1970, 92, 1355–1361, doi:10.1021/ja00708a041.
[21]
Dalling, D.K.; Grant, D.M. Carbon-13 magnetic resonance. IX. The methylcyclohexanes. J. Am. Chem. Soc. 1967, 89, 6612–6622, doi:10.1021/ja01001a039.
[22]
Ribeiro, D.S.; Olivato, P.R.; Rittner, R. Axial/equatorial populations in α-hetero-substituted cyclohexanone Oximes and O-methyl oximes. Magn. Reson. Chem. 2000, 38, 627–638, doi:10.1002/1097-458X(200008)38:8<627::AID-MRC680>3.0.CO;2-M.
[23]
Gultekin, D.D.; Tasxkesenligil, Y.; Dastan, A.; Balci, M. Bromination of norbornene derivatives: Synthesis of brominated norbornanes and norbornenes. Tetrahedron 2008, 64, 4377–4383, doi:10.1016/j.tet.2008.02.067.
[24]
Tonelli, A.E.; Schilling, F.C. 13C NMR chemical shifts and the microstructure of propylene-vinyl chloride copolymers with low propylene content. Macromolecules 1984, 17, 1946–1949, doi:10.1021/ma00140a011.
[25]
Zhang, H.J.; Yi, Y.H.; Yang, G.J.; Hu, M.Y.; Cao, G.D.; Yang, F.; Lin, H.W. Proline-containing cyclopeptides from the marine sponge Phakellia fusca. J. Nat. Prod. 2010, 73, 650–655, doi:10.1021/np9008267.
[26]
Clinical and Laboratory Standards Institute, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi: Approved Standard; NCCLS M38-A2, Clinical Laboratory Standards Institute, Wayne, PA, USA, 2008.
[27]
Clinical and Laboratory Standards Institute, Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts: Approved Standard; NCCLS M27-A3, Clinical and Laboratory Standards Institute, Wayne, PA, USA, 2009.