Camptothecin Quinoline Alkaloids

Camptothecin (84) Quinoline alkaloid Karenitecin Oncology Inhibits topoisomerase I Phase III BioNumerik and 149,... 

Camptothecin (Fig. 4), a quinoline alkaloid, is a potent anti-neoplastic agent that inhibits DNA topoisomerase I. Accumulation of up to 8 mg of camptothecin/L was reported for hairy root cultures of Ophiorriza pumila transformed with A. rhizogenes. Cotyledon-derived calluses of Nothapodytes foetida were able to produce not only camptothecin, but also its derivatives also known to exhibit anticancer activity. 

The pentacyclic quinoline alkaloid camptothecin (1) contains in addition to the quinoline system (rings A and B) a pyndone unit (ring D) and a lactone ring (E) Compound 1 also includes one stereogenic center (at C-20), which has the -configuration... 

Irinotecan (1) is a derivative of the pentacyclic quinoline alkaloid camptothecin (2) the latter was first isolated from the heartwood of the tree species Camptotheca acuminata (Nyssacea) by Wall et al. in 1966.1 Two years later A. T. McPhail and G. A. Sim determined the structure of 2 by X-ray analysis.2... 

Camptothecins. The alkaloid camptothecin from Camptotheca acuminata (Nyssaceae) and Mappiafoetida (Icacinaceae) has a pyranoindolizoquinoline structure (Phe pyridine C4N C5N C5L) involving the fusion of quinoline (Phe pyridine), indolizidine (C4N C5N ) and C5 lactone (C5L) rings. Camptothecin is a topoisomerase I inhibitor and is a potent cytotoxic and antitumour compound that is used clinically as an anticancer... 

A variety of plant substances with planar, polycyclic, aromatic structures can intercalate with DNA, examples being the quinoline alkaloid camptothecin and the furanocoumarin phenolic psoralen (Table 12.1). A variety of plant-derived anthraquinones and naphthoquinones bind to DNA and it is notable that the structurally related anthraquinones mitox-antrone and adriamycin are clinically employed as anticancer drugs (Table 12.1). DNA-binding compounds that interfere with DNA repair, DNA replication and gene expression are cytotoxic and have potential as anticancer agents (see Chapter 9). 

Camptothecin (CRT, 6, Figure 2.2) was first isolated from the Chinese ornamental tree Camptotheca acuminata Decne, also known as the tree of joy and tree oflove. It occurs in different plant parts such as the roots, twigs, and leaves. It is a member of the quinoline alkaloid group and consists of a pentacyclic ring structure that includes a pyrrole quinoline moiety and one asymmetric center within the a-hydroxy lactone... 

Camptothecin, a quinoline alkaloid from Camp-totheca acuminata (Nyssaceae), is derived from strictosi-dine through stiictosamide (Fig. 41). Originally isolated in 1966, it biologically inhibits topoisomerase I, and in 1996, two derivatives, topotecan and irinotecan, were approved for the treatment of ovarian cancer and colon cancer, respectively. Other derivatives are in clinical trial. 

The alkaloids of the cinchona bark are natural products containing a quinoline structure [111]. Examples are the diastereoisomeric pairs quinine/quinidine and cinchonidine/cinchonine 108 and 109 in which a 4-methylquinoline unit is bonded to a vinyl-substituted quinuclidine system (1-azabi-cyclo[2.2.2]octane). Camptothecin 110, a highly toxic polycyclic quinoline alkaloid, was isolated from the stem wood of the Chinese tree Camphoteca acuminata (Nyssaceae). 

A naturally occurring pyrrolo[3,4-Z)]quinoline alkaloid 415, named camptothecin, has a promising antineoplastic activity in animal tumor models. When 415 was irradiated with MW under solvent-free conditions, it gave mappicine ketone 416 in 96% yield within 7 min (Scheme 83) 416 was found to be an antiviral lead compound. Under conventional conditions, 415 reacted with borontrifluoride etherate in THF at room temperature for 1.5 h to give 416 in 65% yield (98TL431). 

Lactones are a class of organic compounds which are prevalent in nature and are a key structural motif in many bioactive molecules and pharmaceuticals (Fig. 1.6). For example camptothecin, a cytotoxic quinoline alkaloid, has shown anti-cancer... 

Camptothecin is a quinoline alkaloid isolated from the steins of C. acuminata (Cornaceae) [1], and 10-hydroxy camptothecin and 10-methoxy camptothecin were also obtained as minor alkaloids [2]. C. acuminata is an ornamental plant in China. Campthothecin has also been isolated from both the Apocy-naceae and Rubiaceae plant families. 

Sivak et al. [149,150] developed biodegradable and biocompatible polyurethane foams for drug-delivery release of 7-tert-butyldimethylsilyl-lO-hydroxy-camptothecin (DB-67) (Figure 12.19), based on lysine diisocyanate (LDI) and glycerol. Camptothecdn (CPT) is a cytotoxic quinoline alkaloid, which exhibit anticancer activity in ovarian. 

Minisci reaction has found ample applications in the synthesis of alkaloids. The selective functionalization in C7 position of camptothecin (1), a naturally occurring quinoline alkaloid, opened the view to new classes of alkyl (2) and acyl (3) derivatives acting as topoisomerase I inhibitors (Scheme 2) [11]. 

Camptothecin is a cytotoxic quinoline alkaloid, which inhibits the DNA enzyme topoisomerase I. It was discovered in 1966 in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of the Chinese tree Camptotheca acuminata. Camptothecin showed remarkable anticancer activity. A fluorinated... 

A combination of a reductive amination and a Michael addition has been used to synthesize the anticancer alkaloid camptothecin (2-955) via 2-954, starting from the quinoline carbaldehyde 2-953 and benzylamine (Scheme 2.214) [487]. 

Using a modified Minisci reaction, the 4-position of the quinoline ring in alkaloid 195 (camptothecin) was substituted to afford the highly active antitumor agent 196 (karenitecin) (Equation 105) <2001USP6194579>. 

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