Antineoplastic alkaloids

Vindoline [2182-14-1] (45), a monomeric Vinca alkaloid intermediate important in the synthesis of antineoplastic alkaloids, is selectively converted in good yield to 0-desmethylvindoline [68687-22-9] (46) by cultures of Sepedonium chrysospermum (17,25), whereas Streptomyces albogriseolus removes only the A[-methyl group to give (47) (91) (see Chemotherapeutics, anticancer). 

Intercalation has been demonstrated with a number of other compounds having a polycyclic aromatic system and groups capable of forming hydrogen bonds. Among such compounds are the antibacterial 9-aminoacridine, the antimalarials mepacrine and chloroquine, the veterinary trypanocide ethidium (246), the thioxanthone lucanthone (247 R = Me) and its more active metabolite hycanthone (247 R = CH20H), which are used in the treatment of schistosomiasis, and the antineoplastic alkaloid ellipticine (248). A number of antibiotics, including the actinomycins, echinomycin and bleomycin, also intercalate. 

The reaction provides a key step in a synthesis of the antineoplastic alkaloid tylophorine (3). 

The mode of action of the harringtonines has been investigated. All inhibit protein synthesis in eukaryotic cells (190-192). The principal effect of harringtonine was inhibition of protein biosynthesis in HeLa cells (193). Homoharringtonine, a potential antineoplastic alkaloid (191), was cytotoxic in HeLa, KB, and L cells growing in monolayer cell cultures (194). 

Chinese workers have continued their pharmacological exploration of esters of cephalotaxine (3a) and have reported the transformation of this alkaloid into harringtonine (26a)12 and 0-(2-oxo-5-methylhexanoyl)cephalotaxine (26b).13 The latter compound is an intermediate in the synthesis of the antineoplastic alkaloid deoxyharringtonine (26c). The overall conversion of cephalotaxine into deoxyhar-ringtonine (26c) via (26b) has been patented.14 Of twenty-two esters of (-)-... 

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]. 

Naito and co-workers employed an oxazole ring as a template to constmct the piperidine ring of the novel antineoplastic alkaloids, pseudodistomin A and B, 1151 and 1152, respectively. This work was the first synthesis of pseudodistomin... 

Vinca minor, V. major— the common periwinkles—contain numerous indole alkaloids including vincamine, majdine, majoridine. Their actions are antihaemorrhagic and astringent. Vinca spp. do not contain the antineoplastic alkaloids found in Cantharanthus (Wren 1988). 

Kobayashi, J., Cheng, J.-F., Yamamura, S., and Ishibashi, M. (1991e) Revised structures of prianosins C and D, antineoplastic alkaloids from the Okinawan marine sponge Prianos mdanos. Tetrahedron Lett., 32, 1227-1228. 

Utsunomiya, I., Ogawa, M and Natsume, M. (1992) Synffiesis of ( )-tetrahydropseudodistomin, a hydrogenation product of antineoplastic alkaloids, pseudodistomins A and B. Heterocydes, 33, 349-356. 

In regard to the antineoplastic properties of Rutaceae, this family has attracted a great deal of interest for its ability to elaborate series of cytotoxic benzo[c]phenanthri-dine and acridin alkaloids. Examples of acridin alkaloid are pyrano-acridone and acronycine characterized from Acronychia baueri Scott. 

Examples of acridin alkaloids used in therapeutics as antineoplastic agents is amsacrine (Amsa P-D ), which is used for the treatment of acute leukemia in adults and malignant lymphomas, refractory to conventional therapy. Amsacrin is an intercalating agent and topoisomerase II inhibitor. 

The binary indole-indoline alkaloids vinblastine (VLB, 1) and vincristine (VCR, 2) (Fig. 1) have triggered considerable chemical investigation as a result of their extensive clinical use as antineoplastic agents (2-4), coupled with an arduous isolation from plant material, and because of... 

The Ley research group [76] developed a flow process for the multistep synthesis of ( )-oxomaritidine, an alkaloid found in the Amaryllidaceae family, known to have antineoplastic activity (Scheme 34) [77, 78]. The route does not involve intermediate purification of the products, which is necessary in the previously reported... 

Vinblastine (Velban, Velbe) [Antineoplastic/Vinca Alkaloid]... 

ALKALOIDS WITH ANTINEOPLASTIC AND OTHER TYPES OF BIOLOGICAL ACTIVITY 50... 

In addition to the antineoplastic activity, camptothecin was found to be an effective inhibitor of adenovirus replication [268, 269] and herpes virus replication [252, 270]. 10-Methoxycamptothecin is about 8-times more potent than camptothecin as an inhibitor of herpes virus [252]. A combination of camptothecin and dimethyl sulphoxide is very effective for the topical treatment of psoriasis [271]. Since, in the goldfish brain, camptothecin blocks RNA synthesis in eucaryotic cells by blocking the incorporation of uridine into RNA, this alkaloid can block the memory of conditioned avoidance and produces no measurable effect on retention of the learned response [272]. 

---