Camptotheca alkaloids

Higher plants have yielded many effective, clinically useful anticancer drugs, including those derived from Catharanthus alkaloids, Taxus diterpenes, Camptotheca alkaloids, and Podophyllum lignans. Research in this area has been reviewed extensively (3-13). 

Camptothecin is a plant alkaloid obtained from the Camptotheca acuminata tree. It was first evaluated clinically, as a sodium salt, in the 1960s and 1970s, but was abandoned because of severe and unpredictable hemorrhagic cystitis (3,4). Irinotecan (CPT-11) and Rubetecan are semisynthetic, water-soluble derivatives of camptothecin possessing... 

Indole alkaloids Tryptophane decarboxylase Catharanthus roseus Camptotheca acuminata... 

Camptothecin, an alkaloid isolated from a Chinese tree Camptotheca acuminate), is a potent cytotoxic agent, acting by the inhibition of DNA topoisomerase I. Derivatives that are fluorinated on the aromatic ring A have been studied, leading to two drug candidates for cancer therapies (Figure 8.7) ° exatecan is in Phase IB development,and diflomotecan is an E-homocamptothecin currently in Phase II trials for several solid cancers. 

Only the antitumor alkaloids of Camptotheca have been reported. Davidia involucrata, as tested here, was positive (1/3) (it is sometimes placed in a family of its own, Davidiaceae) three species of Nyssa were negative N. biflora, N. ogeche, N. sylvatica. 

Another important anticancer natural product is camptothecin, an alkaloid derived from the Chinese tree Camptotheca acuminata Descne. A semisynthetic water-soluble derivative of camptothecin known as ironotecan (Topotecin , Campto ) was introduced in Japan in 1994 for the treatment of lung, ovarian, and cervical cancers. Unlike Taxol, camptothecin acts by inhibition of the enzyme topoisomerase I. 

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... 

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... 

Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA. 64. Plant antitumor agents. 1. The isolation and structure of camp-tothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J. Am. Chem. Soc. 1966 88 3888-3890. 

Camptothecin (CPT, Cl) is a potent antitumor pentacyclic alkaloid isolated from Camptotheca acuminata Decne. (Nyssaceae family) and originating in China (36, 37). Interest in CPT was sparked by the discovery that its primary cellular target is DNA topo I (38). 10-Hydroxycamptothecin (C2), which also occurs naturally, has a better therapeutic index and is used in China for treating many cancers. 

Quinoline alkaloids Camptotheca acuminata CCI4 CHCl3-Me0H-H20 (2 2 3 1), CH2CI2-CHCI3 MeOH-H20 (5 3 1) HSCCC... 

Camptothecin, a plant alkaloid derived from Camptotheca acuminata, is a potent inhibitor of DNA topoisomerase I. Clinical trials failed to show expected antitumor activity, and the drug produced severe, unpredictable toxicity. The camptothecin analogs irinotecan and topotecan were synthesized to reduce toxicity and improve therapeutic... 

The alkaloid camptothecin (66) from Camptotheca acuminata (Nyssac.) has created much interest recently.When tested against leukaemia L-1210 in mice... 

The parent camptothecin alkaloid, isolated from bark of Camptotheca acuminate, has antitumor activity, but its limited water solubility necessitated delivery as ... 

Camptothecine isolated from Camptotheca acuminata is also an antineoplastic alkaloid, but is very toxic. Chemical modification have decreased its toxicity, and the compound (6) is now in use as a clinical agent [2]. 

The first mention of the production of the antitumor alkaloid camptothecin (45) by means of Camptotheca acuminata cell cultures was reported by Misawa (735). Sakato and Misawa studied the cell cultures of this plant in more detail, resulting in a cell suspension culture which produced 2.5 /u.g/g dry weight of the alkaloid (734,735), which is considerably lower than the intact plant. 

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