Cytotoxicity of Isoquinoline Alkaloids and TheirN-Oxides¹

Abstract

A series of 53 isoquinoline alkaloids and their N-oxides have been tested for their cytotoxicity against A-549, HCT-8, KB, P-388, and L-1210 cells. These alkaloids include two tetrahydroprotoberberines, two protoberberines, six aporphines, one morphinandienone, five oxoaporphines, seven phenanthrenes, one spirobenzylisoquinoline N-oxide, nine aporphine N-oxides, seven benzyltetrahydroisoquinoline N-oxides, one benzylisoquinoline N-oxide, one protopine N-oxide, three tetrahydroprotoberberine N-oxides, four pavine N-oxides, and four phenanthrene N-oxides. The results are discussed on the basis of structure-activity relationships.

Biotransformation and pharmacokinetics of the novel anticancer drug, SYUIQ-5, in the rat

“…It is unknown if the N-oxide of SYUIQ-5 has cytotoxic activity. Some N-oxides possess tumor cell killing effect [33,34]. In addition, secondary and tertiary amines are subject to conjugation reactions such as glucuronidation.…”

Naturally occurring plant isoquinoline N-oxide alkaloids: Their pharmacological and SAR activities

“…Apparently, there is a close relationship between the structures of alkaloids and the affinity for some sites in microbial cells (Abidov et al 1962(Abidov et al ,1963Tsai et al 1989;Wu et al 1988).…”

“…11-hydroxylated, 11-methoxylated and 8-oxo-alkaloids (crystamidine and erysotramidine) and erybidine, not described previously in these species were also detected. Erysotrine N-oxide (79) 18 (37,39,(94)(95)(96)(97)(98), one benzyl-isoquinoline N-oxide (99), one protopine N-oxide (102), three tetrahydro-protoberberine N-oxides (103-105), three pavine N-oxides (7, 11, 100), and four phenanthrene N-oxides (83-86) (Wu et al 1989). The fact that all other tested isoquinoline N-oxide alkaloids showed only marginal activity against KB cells (Ioanoviciu et al 2005;Mayr et al 1997;Tan et al 1991).…”

“…Antimicrobial activity of isoquinoline N-oxide alkaloids: D-(-)-armepavine N-oxide (39), D-(+)-Nmethylcoclaurine N-oxide (97), ()-tetrahydro-palmatine N-oxide (103), (+)-laudanidine N-oxide (37); dicentrine methine N-oxide (84), eschscholtzine N-oxide (11, and 81) isolated from Formosan annonaceous plants against bacteria and yeasts: Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella paratyphi B, Escherichia coli, Streptococcus hemolyticus, Candida albicans, and Cryptococcus neoformans has been reported (Letasiova et al 2005;Tsai et al 1989;Wu et al 1988). The antimicrobial activity of 23 isoquinoline alkaloids from Turkish Fumaria and Corydalis species was detected, and many alkaloids displayed a significant activity against Grampositive and Gram-negative bacteria at 1 g/ml concentration.…”

Traditional Chinese Medicine Active Ingredient-Metal Based Anticancer Agents

“…5) is an oxoaporphine alkaloid that has been isolated from overground parts of plants belonging to different families such as Annonaceae (Chang et al, 1998;Chen et al, 1996), Lauraceae (Chen et al, 1998), Magnoliaceae (Chen et al, 1976), Fumariaceae (Blanco et al, 1993;Tojo et al, 1991), Menispermaceae (Ohiri et al, 1982) and Papveraceae (Sari, 1999), which is also found widely exist in many traditional Chinese medicine, such as aquilegia ecalcarata Maxim (Ranunculaceae) mainly distributed in Sichuan and Yunnan Provinces of China and used for the treatment of necrotic boils, pustulosis and other infections . The primary screening results reveal that oxoglaucine possesses strong anticancer activity, such as against HCT-8 (ED 50 = 1.00 µg/ml) and K B (ED 50 = 2.00 µg/ml) (Chang et al, 2002;Chen et al, 2002;Wu et al, 1989). In addition, oxoglaucine exhibits other important pharmacological activities including antiplatelet aggregation (Chang et al, 1998;Jantan et al, 2006), immunomodulatory activity (Ivanovska et al, 1997 and2000), treatment of adjuvant arthritis , antiinflammatory (Remichkova et al, 2009), antifungal activity (Clark et al, 1987).…”