Anti-neoplasmic activity

Ethyl 2-ethylthio-4-chloro-5-pyrimidinecarboxylate (XXIIa), as well as the corresponding4-hydroxy-(XXIIb) and 4-amino-(XXIIIa) derivatives, possess-anti-cytogenic activity on Neurospora crassa [223, 224]. Compounds (XXIIIa, b and c) were found to inhibit the conversion of orotic acid to the uridine nucleotides [202]. Ethyl 2-methylthio-4-(halo-substituted anilino)-5-pyrimidinecarboxylates (XXIV), particularly the o-bromo- and the o-chloro- derivatives, substantially inhibit the growth of five experimental mouse tumours (Krebs-2 ascites carcinoma, Ehrlich carcinoma clone 2, leukaemia L-1210, carcinoma 755 and lymphocytic neoplasm P-288) [225]. Compounds of this type are usually prepared by the base catalysed condensation of ethoxymethylenemalonic esters or related derivatives with urea, thiourea, guanidine, or substituted amidine-type analogues [212, 225-237]. 

VLB and VCR have shown significant differences in their clinical activity against human neoplasm. VLB is preferred in the treatment of Hodgkin s disease because of its better tolerance. VCR is superior to VLB in the treatment of lymphosarcoma, but this is in part counterbalanced by its greater toxicity. The combined use of VLB and VCR has also been discussed. Dihydro-VLB is much less toxic to animals, and its anti-tumour activity is lower than that of VLB, but the response differs from VLB. ... 

Podophyllotoxin (5./7), from Podophyllum peltatum, the tropical squirting cucumber , strongly inhibits the polymerization of tubulin and is used in dermatology to destroy warts and other skin neoplasms. Deoxy-podophyllo-toxin, from the berries of the juniper tree, has anti-viral activity. Etoposide, a semi-synthetic derivative of podophyllotoxin, is used clinically for the treatment of otherwise fatal tumours. Chemically it is demethyl-1-0-(4,6-0-ethylidene-)8-D-glucopyranosyl)epipodophyllotoxin. It does not seem to prevent the synthesis of microtubules, but a decrease in DNA synthesis is noted (Loike, 1984). 

Hemangiopericytoma is a highly cellular and mitotically active neoplasm that is rich in pericellular reticulin and stainable with anti-type IV collagen. Eighty percent of these tumors recur, and 23% metastasize. > 8i... 

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