Nothapodytes foetida, camptothecin

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. 

Thengane SR, Kulkami DK, Shrikhande VA, Joshi SP, Sonawane KB, Krishnamurthy KV. (2003) Influence of medium composition on callus induction and camptothecin(s) accumulation in Nothapodytes foetida. Plant Cell Tissue Organ Cult 72 247-251. 

Puri SC, Verma V, AmnaT, Qazi GN, Spiteller M, An endophytic fungus from Nothapodytes foetida that produces camptothecin, J Nat Prod 68 1717—1719,... 

The Indian tree Nothapodytes foetida (syn. Mappia foetida) is an important source of camptothecin, the DNA topoisomerase I inhibitor possessing anti-cancer and anti-HIV activity of significant therapeutic importance. One of the minor components of the plant has been identified as 9-methoxy-20-(S)-mappicine, a tetracyclic derivative of the pentacyclic camptothecin. When the latter compound was treated for a short-time (7 min) with microwave irradiation, it was converted into 9-methoxymappicine ketone with an exceptionally high yield of 95%. This ketone was then easily transformed by baker s yeast into the target compound 9-methoxy-20-(S)-mappicine as illustrated in Fig. 15 [91]. 

Camptothecin (CPT, 1) is a natural compound isolated for the first time [1] from the wood of Camptotheca acuminata Decne (Nyssaceae), a deciduous plant (xi shu, happy tree) of Southeastern China, but produced also by the Indian Icacinacea Nothapodytes foetida (Wight) Sleumer (formerly Mappia foetida Miers) [2], and by some other plants [3], the two former being the major sources of the compound. 

A survey of the distribution of camptothecin and its metabolites has been published. The compounds are still obtained from the bark and seeds of C. acuminata and Nothapodytes foetida. Recent studies with hairy root cultures of C. acuminata and Ophiorrhiza pumila indicate that plant tissue culture methods of production may prove feasible in the future. ... 

Camptothecin (1) was first isolated from Camptotheca acuminata Decne (Nyssaceae) [1, 39] which has been used for many years as a traditional Chinese medicine. Extensive studies of the natural distribution of this unique alkaloid led to its isolation from several plant families Nothapodytes foetida [40-43], Ophiorrhiza mangos [44], Ervatmia heyneana [45], Merrilliodendron... 

Hsiao H-Y, Cheng T-J, Yang G-M, Huang I-J, Chen RLC (2008) Determination of camptothecins in DMSO extracts of Nothapodytes foetida by direct injection capillary electrophoresis. Phytochem Anal 19 136-140. doi 10.1002/pca.l026... 

Besides camptothecines, structurally related (having the same tetracyclic ll//-indolizino[l,2-b]qumolme-9-one core) alkaloids such as 18,19-dehydro-CPT 16, mappicine 17 [86], nothapodytine, A and mappicine ketone 18 [87] (Fig. 22.4) and their hydroxylated or methoxylated derivatives and glucosides were isolated from Nothapodytes foetida (Icacinaceae) [65, 71, 76, 78, 81, 82],... 

Nothapodytes foetida (Icacinaceae) (55, 56). From Ophiorrhiza mungos (Rubi-aceae), camptothecin and 10-methoxycamptothecin have been obtained, and from Ervatamia heyneana (Apocynaceae), camptothecin and 9-methoxycamptothecin (59). From Merrilliodendron megacarpum (Icacinaceae), camptothecin and 9-methoxycamptothecin have been isolated (3). Table 5.2.5 lists yields from various plants. 

The initial source plant of camptothecin, Camptotheca acuminata, is a rare species found in southern regions of the People s Republic of China. Today, camptothecin is produced commercially not only from cultivated C. acuminata trees in mainland China but also from the roots of Nothapodytes nimmoniana (formerly known as both N. foetida and Mappia foetida), which is found in the southern regions of the Indian subcontinent (69). Interestingly, these two antineoplastic agents are particularly important both because of the clinical effectiveness of their derivatives as cancer chemotherapeutic agents and because they are prominent lead... 

In addition to Camptotheca acuminata (Nyssaceae), camptothecine (6) has been found in Nothapodytes (Mappia) foetida and Merilliodendron megacarpum (Icacinaceae), Ophionhiza mungos (Rubiaceae), and Ervatamia heyneana (Apocynaceae) (Cordell, 1981). This distribution is of considerable interest to plant systematists and phylogenists, as it reflects the same dichotomy seen in the distribution of other types of monoterpene iridoids. 

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