Anti-tumor activities

Considerable attention is also being given to the anti-tumor activity of titanium compounds. 

Hagan et al. utilized the Graebe-Ullmann process to synthesize polycyclic acridines 14 which exhibit anti-tumor activity. ... 

Enhancement of anti-tumor activity of 1-p-D-arabino-furanosylcytosine by encapsulation, Int. J. Cancer. 20, 581-587. 

Upadhyay KK, Bhatt AN, Mishra AK, Dwarakanath BS, Jain S, Schatz C, Le Meins JE, Earooque A, Chandraiah G, Jain AK, Misra A, Lecommandoux S (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(y-benzyl L-glutamate)-b-hyaluronan polymersomes. Biomaterials 31(10) 2882... 

Another class of DNA alkylating agents, the Mitomycins, proved to be most promising in clinical trials. Among these, mitomycin C, shown in Fig. 6.1, exhibits significant anti-tumor activity. Its mechanism of activation consists of a complex bioreductive process. The first step is the reduction to hydroquinone, followed by a loss of methanol. This reaction fa-... 

These chlorobenzocycloheptapyridines display pronounced selectivity for FTase over GGTase I. They show improved in vivo anti-tumor activity and pharmacokinetic profiles in mice when administered orally and inhibit H-Ras processing in Cos monkey kidney cells [43,44]. Extensive variation of the substituents on the piperidine moiety and the tricyclic ring system led to the devel-... 

Rebeccamycin derivatives represent a third generation of topi inhibitors the maleimidoindolocarbazole. Since the structural identification in 1984 [15], rebeccamycins have attracted interest for their anti-tumor activity. Recently,... 

Arakawa H, Morita M, Kodera T, Okura A, Ohkubo M, Morishima H, et al. In vivo anti-tumor activity of a novel indolocarbazole compound, J-107088, on murine and human tumors transplanted into mice. Jpn. J. Cancer Res. 1999 Oct 90(10) 1163-70. 

Zhu G, Oto E, Vaage J, et al. The effect of vincristine-polyanion complexes in STEALTH liposomes on pharmacokinetics, toxicity and anti tumor activity. Cancer Chemother Pharmacol 1996 39 138. 

Allen TM, Newman MS, Woodle MC, et al. Pharmacokinetics and anti-tumor activity of vincristine encapsulated in sterically stabilized liposomes. Int J... 

Zhao E, He EQ, Wang L, Liu K. (2008) Anti-tumor activities of andrographolide, a diterpene from Andrographis paniculata, by inducing apoptosis and inhibiting VEGF level. J Asian Nat Prod Res 10 413-419. 

Histone deacetylases are linked to the pathogenesis of malignancy from a mechanistic perspective. The capacity of HDAC inhibitors (HDACi) to interfere with the enzyme fimction has led to the observed prechnical and clinical activity in cancer therapy. Although the exact mechanism of anti-tumor activity is not fully elucidated, various cellular pathways have been shown to be involved. From the first chnical trials involving HDACi with short chain fatty acids to the newer generation hydroxamic acid derivatives and cychc tetrapeptides, a number of structurally diverse compounds have made the transition from the laboratory to the chnical arena. For purposes of this part of the discussion, HDACi are arbitrarily divided into the hydroxamates and nonhydroxamates. 

In 1984, Giibble et al. reported for the first time a novel l,10-bis-(6-methyl-5H-benzo[fc]carbazol-ll-yl)decane (469) which has potential bifunctional nucleic acid intercalating properties (406). To function as anti-tumor active drugs, one of the most important cytostatic mechanisms of action of coplanar annelated polycyclic compounds is their intercalation with DNA (405). Ten years later, Kucklander et al. studied a series of 5H-benzo[ 7]carbazole quinone derivatives for their cytotoxic activity against colon and lung cancer cells, and found that the heteroannelated 5H-benzo[ 7]carbazole quinone derivative 470 was the most active among the various analogs (407) (Scheme 4.2). 

Coriolin (689), a metabolite of the Basidiomycete Coriolus consors, has attracted widespread interest because of its unusual anti-tumor activity and highly functionalized triquinane structure. Accordingly, a number of syntheses of689 have appeared on the scene. One of the earliest, due to Tatsuta, et al., begins with epoxide 690, whose preparation had been earlier realized in connection with their work on hirsutine (see Scheme LXIII). Deoxygenation of 690, hydrolysis, and cis-hydroxy-lation provided keto triol 691 (Scheme LXXII) The derived acetonide was transformed via 692 into tetraol 693 which could be selectively acetylated and dehydrated on both flanks of the carbonyl group. Deacetylation of 694 followed by epoxidation completed the synthesis. 

Carboplatin is a platinum complex in which platinum is incorporated into a more complex molecule. Its mechanism of action and spectrum of anti-tumor activity are similar to those of cisplatin. However carboplatin is better tolerated that cisplatin. 

CS144 Sato, A. Studies on anti-tumor activ- CS155 ity of crude drugs. 1. The effects of aqueous extracts of some crude drugs in short-term screening test. Yaku-gaku Zasshi 1989 109(6) 407-423. 

Anti-tumor activity. Water extract of the dried seed, administered intraperitoneally to mice, was active on CA-755 cells . Hot water extract of the dried seed, administered in the drinking water of mice at a concentration of 0.5%, was active on spontaneous mammary tumors °. 

Anti-implantation effect. Chloroform extracts of the dried leaf, twig, and stem, administered intragastrically to pregnant rats at a dose of 0.58 g/kg for 10 days, were active. The phenolic fraction, at a dose of 0.52 g/kg and methanol extract at a dose of 0.70 g/kg, were active. Water extract, at a dose of 1 g/kg and petroleum ether extract at a dose of 0.38 g/kg, were inactive Anti-tumor activity. Water extract of the dried root, administered intraperitoneally to mice at a dose of 400 mg/kg, was inactive on Leuk (friend virus-solid) and Leuk-L1210. A dose of 500 mg/kg was inactive on sarcoma 180(ASC) - . 

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