Cytotoxic Aporphine Alkaloids from Ocotea acutifolia

Abstract

Two new aporphinoid alkaloids, (+)-6S-ocoteine N-oxide and (+)-norocoxylonine, were isolated from the leaves and trunk bark of Ocotea acutifolia (Lauraceae) along with thirteen aporphine analogues, one morphinan alkaloid, and one flavonoid. The aporphine alkaloids (+)-thalicsimidine and (+)-neolitsine are reported for the first time for the genus Ocotea. The structures of all compounds were established on the basis of 1D- and 2D‐NMR spectroscopic techniques, optical rotation and/or mass spectrometry data. The cytotoxic potential of eight of the aporphine alkaloids against four human cancer cell lines (Hep-2, MCF-7, B16-F10 and 786-0) was also evaluated.

Key words

Ocotea acutifolia - Lauraceae - N-oxide aporphine alkaloids - SRB assay

References

• 1 Rios J L, Manez S, Giner R M, Recio M C. Biological aspects of aporphinoid alkaloids. Cordell GA The alkaloids, Vol. 53. San Diego; Academic Press 2000: 57-117
• 2 Stévigny C, Bailly C, Quetin-Leclercq J. Cytotoxic and antitumor potentialities of aporphinoid alkaloids.  Curr Med Chem Anticancer Agents. 2005;  5 173-182
• 3 Wu Y C, Liou Y F, Lu S T, Chen C H, Chang J J, Lee K H. Antitumor agents. CIII. Cytotoxicity of isoquinoline alkaloids and their N-oxides.  Planta Med. 1989;  55 163-165
• 4 Garcez F R, Garcez W S, Martins M, Matos M F C, Guterres Z R, Mantovani M S, Misu C K, Nakashita S T. Cytotoxic and genotoxic butanolides and lignans from Aiouea trinervis.  Planta Med. 2005;  71 923-927
• 5 Garcez F R, Garcez W S, Martins M, Cruz A C. A bioctive lactone from Nectandra gardneri.  Planta Med. 1999;  65 775
• 6 Skehan P, Shoemaker R, Pau K, Vistica D, Curtis H, Langley J, Cronise P, Vaigro-Wolff A, Gray-Goodrich M, Campbell H, Mayo J, Boyd M. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines.  J Natl Cancer Inst. 1991;  83 757-766
• 7 Finney D J. Probit analysis. 3rd edition. Cambridge; Cambridge University Press 1971: 1-333
• 8 Guinaudeau H, Leboueuf M, Cavé A. Aporphine alkaloids, II.  J Nat Prod. 1979;  42 325-360
• 9 Zanin S M, Lordello A L L. Alcaloides aporfinóides do gênero Ocotea (Lauraceae).  Quim Nova. 2007;  30 92-98
• 10 Marsaioli A J, Reis F A M, Magalhães A F, Rúveda E A, Kuck A M. Carbon-13 NMR analysis of aporphine alkaloids.  Phytochemistry. 1979;  18 165-169
• 11 Guinaudeau H, Leboueuf M, Cavé A. Aporphine alkaloids.  Lloydia. 1975;  38 275-338
• 12 Guinaudeau H, Leboueuf M, Cavé A. Aporphinoid alkaloids, V.  J Nat Prod. 1994;  57 1033-1135
• 13 Guinaudeau H, Leboueuf M, Cavé A. Aporphinoid alkaloids, IV.  J Nat Prod. 1988;  51 389-474
• 14 Montgomery C T, Freyer A J, Guinaudeau H, Shamma M, Fagbule M O, Olatunji G. (+)-N-methyllaurotetanine-β-N-oxide from Glossocalyx brevipes.  J Nat Prod. 1985;  48 833-834
• 15 Ma W G, Fukushi Y, Tahara S, Osawa T. Fungitoxic alkaloids from Hokkaido Papaveraceae.  Fitoterapia. 2000;  71 527-534
• 16 Roblot F, Hocquemiller R, Cave A. Study of morphinandienones: carbon-13 and proton NMR of sebiferine and related alkaloids.  Bull Soc Chim Fr. 1984;  3–4 139-141
• 17 Kametani T, Ihara M, Honda T. Two new alkaloids; kikernanine and the morphinandienone-type alkaloid, pallidine, from Corydalis species.  Chem Commun. 1969;  1301
• 18 Wright C W, Marshall S J, Russell P F, Anderson M M, Phillipson J D, Kirby G C, Warhurst D C, Schiff jr. P L. In vitro antiplasmodial, antiamoebic, and cytotoxic activities of some monomeric isoquinoline alkaloids.  J Nat Prod. 2000;  63 1638-1640
• 19 Stévigny C, Block S, De Pauw-Gillet M C, Hoffmann E, Llabrès G, Adjakidjé V, Quetin-Leclercq J. Cytotoxic aporphine alkaloids from Cassytha filiformis.  Planta Med. 2002;  68 1042-1044
• 20 Likhitwitayawuid K, Angerhofer C K, Chai H, Pezzuto J M, Cordell G A, Ruangrungsi N. Traditional medicinal plants of Thailand. XXIII. Cytotoxic and antimalarial alkaloids from the tubers of Stephania pierrei.  J Nat Prod. 1993;  56 1468-1478
• 21 Huang R L, Chen C C, Huang Y L, Ou J C, Hu C P, Chen C F, Chang C. Anti-tumor effects of d-dicentrine from the root of Lindera megaphylla.  Planta Med. 1998;  64 212-215