Neoplastic activity

Epi-(Z)-isositsirikine. 16-Epi-(Z)-isositsirikine (48) displays in vivo anti-neoplastic activity in the KP as well as P 388 test systems (57). 

Mantel, N. (1980). Assessing laboratory evidence for neoplastic activity. Biometrics 36 381— 399. 

In contrast to the effects of secondary bile acids like DCA, UDCA, which is found at a high concentration in bear bile but only in trace amounts in humans, has anti-neoplastic activity in vitro and in vivo. UDCA has significant chemopreventative activity in rodent models of sporadic and colitis-colorectal carcinogenesis induced by chemical carcinogens. 

Figure 5.2 Therapeutic interventions for decreasing colorectal mucosal bile acid exposure as a CRC chemoprevention strategy. 1) Lifestyle modifications including reduction in dietary animal fat and increased fibre intake may, at least partly, be explained by reduction in luminal primary (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary (deoxycholic acid [DCA] and lithocholic acid [LCA]) bile acids. 2) Reduction of secondary bile acids, which are believed to have pro-carcinogenic activity could be obtained by decreased bacterial conversion from primary bile acids. 3) Alternatively, bile acids could be sequestered by chemical binding agents, e.g. aluminium hydroxide (Al(OH)3) or probiotic bacteria. 4) Exogenous ursodeoxycholic acid (UDCA) can reduce the luminal proportion of secondary bile acids and also has direct anti-neoplastic activity on colonocytes in vitro.

The mechanistic basis of the anti-neoplastic activity of UDCA and the explanation for the significant difference in bioactivity of UDCA compared with DCA despite marked similarity in chemical structure remain unresolved. UDCA administration in healthy volunteers and colorectal adenoma patients has been demonstrated to decrease the proportion of DCA in aqueous phase stool. Therefore, one possible mechanism of the chemopreventative activity of UDCA is reduction of mucosal secondary bile acid exposure. Consistent with this idea, UDCA administration has been demonstrated to reduce the incidence of K-ras mutations and decrease Cox-2 expression in AOM-induced tumors, which is the opposite of the reported effects of DCA in the same model. However, it is clear that exogenous administration of UDCA has direct anti-neoplastic activity on human CRC cells in vitro, either alone or in combination with DCA, including anti-proliferative and anti-apoptotic effects, as well as induction of cell senescence. " ... 

Anti-neoplastic activity of UDCA was demonstrated first in the context of ulcerative colitis-associated colorectal carcinogenesis. Subsequently, encouraging (but not definitive) results have been obtained in clinical trials of UDCA for prevention of sporadic colorectal adenoma recurrence, which should prompt further evaluation of UDCA for polyp prevention, particularly given its excellent safety profile compared with other candidate chemoprevention agents such as the nonsteroidal anti-inflammatory drugs. 

Phenanthrenebiguanides possess 384) some activity against cancer. The effect of biguanides on plasma protein surface has been investigated 294, 610) with a view to the possibility of finding anti-tumor ents. Aryl-and naphthyl-biguanides exhibit 625) a slight anti-neoplastic activity in vitro in Ehrlich ascites carcinoma. 

Omnitrope should not be used when there is any evidence of neoplastic activity. Intracranial lesions must be inactive and antitumor therapy complete prior to the institution of therapy Omnitrope should be discontinued if there is evidence of tumor growth... 

The anti-neoplastic activity of podophyllotoxin and derivatives has prompted continuous development into clinical agents for treatment of human neoplasia. The semi-synthetic 4 -demethylepipodophyllotoxin derivatives, Etoposide (139) and Teniposide (140). developed by a Sandoz (Basel) group have attracted considerable attention (135-137) (Scheme 28). They have established antitumour activity with lesser toxicity and mechanism of action differing from podophylloxin itself. 

Johns, D. G., Farquhar, D., Chabner, B. A., Wolpert, M. K., Adamson, R. H. Anti-neoplastic activity of lipid-soluble dialkyl esters of methotrexate. Experientia 29, 1104(1973). 

In vitro studies have shown that vanadyl very effectively cleaves DNA in the presence of peroxide. Apart from the possible beneficial effect of this process in anti-neoplastic activity, toxic effects pertinent to vanadium -damage of DNA of healthy cells — has to be taken into account. 

Bajaj, S., Sambi, S.S. and Madan, A.K. (2006b) Models for prediction of anti-neoplastic activity of l,2-bis(sulfonyl)-l-methyIhydrazines computational approach using Wiener s indices. MATCH Commun. Math. Comput. Chan., 55, 193-204. 

Roberts J, Holcenberg )S, Dolowy WC. Anti-neoplastic activity of highly purified bacterial glutaminases. Nature 227(263) 1136-1137, 1970. 

Brefeldin (96), an octaketide macrolide with antiviral, cytotoxic, can-cerostatic and phytotoxic activity, was active (50 jig/ml) towards Anguil-lula aceti [142, 157]. Radicicol (monorden) (97), a macrolide antibiotic produced by Deuteromycetes, possesses cytotoxic, antiprotozoal and anti-neoplastic activity [158]. The diethyl ether derivative showed weak activity (LD50 0.2 mg/ml) against a soil nematode, but the cytotoxicity was considerably higher (LD50 3.1 ig/ml) [159]. 

There are various compounds that exert neoplastic activity both belonging to synthetie and natural origins. A few such compounds are deseribed below ... 

Rossini, G.P., Neoplastic activity of DSP toxins the effects ok okadaic acid and related compounds on cell proliferation tumor promotion or induction of apoptosis , in Seafood and Freshwater Toxins. Pharmacology, Physiology and Detection, Botana, L.M., Ed., Marcel Dekker, New York, 2000, 257. 

Mr 330.37, oil, [a]g -30° (CH3OH). Anti-neoplastically active cfr,cis,cis- germacranolide from the Paraguayan medicinal p ant Acanthospermum aus-trale ( Tapecue ). 

Saframycins. An antibiotic complex (to date 22 known components) from cultures of Streptomyces la-vendulae. The S. contain tetrahydroisoquinoline units dimerized via a piperazine structure. They have anti-neoplastic activity and are active against Gram-positive bacteria, e. g., S. B C2gH3,N308, Mr 537.57, orange prisms, mp. 108-109 C, [a]g,°-54.4° (CH3OH). 

Prostaglandins A and J have a cyclopentanone ring structure which is characterized by the presence of a chemically reactive a,P-unsaturated carbonyl group (Figure 1). Various members of this family have antiviral, antiinflammatory and anti-neoplastic activities. In contrast to other prostanoids... 

Choueiri TK, Wesolowski R, Mekhail TM (2006) Phenoxodiol isoflavone analog with anti-neoplastic activity. Curr Oncol Rep 8 104—107... 

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