Synthesis anticancer drug

Zhang Y, Huo M, Zhou J, Yu D, Wu Y. Potential of amphiphilically modified low molecular weight chitosan as a novel carrier for hydrophobic anticancer drug Synthesis, characterization, miceUization and cytotoxicity evaluation. Carbohydr Polym. 2009 77(2) 231-8. 

A. Pendri, C.W. Gilbert, S. Soundararajan, D. Bolikal, R.G.L. Short, R.B. Greenwald, PEG modified anticancer drugs synthesis and biological activity. J. Bioact. Compat. Polym., 11 (2) 122-134, 1996. 

Folic acid, 4-amino-4-deoxy-10-methyl-, 1, 164 3, 325 as anticancer drug, 1, 263 biological activity, 3, 325 Folic acid, 4-amino-10-methyl-toxicity, 1, 141 Folic acid, 7,8-dihydro-biosynthesis, 3, 320 synthesis, 1, 161, 3, 307 Folic acid, 4-dimethylamino-hydrolysis, 3, 294 Folic acid, 5-formiminotetrahydro-biological activity, 3, 325 Folic acid, 5-formyl-5,6,7,8-tetrahydro-biological activity, 3, 325 chirality, 3, 281 occurrence, 3, 325 Folic acid, 10-forfnyltetrahydro-biological activity, 3, 325 Folic acid, 5,10-methenyl-5,6,7,8-tetrahydro-biological activity, 3, 325 chirality, 3, 281 Folic acid, 5-methyl-chirality, 3, 281 Folic acid, 9-methyl-toxicity, 1, 141... 

Camptothecin was discovered as an active anticancer drug isolated from the bark of Camptotheca acuminata. The anticancer activity of camptothecin was discovered in the 1960s by the National Cancer Institute (NCI) as part of a systematic effort to screen for novel anticancer agents derived from natural products. Monroe Wall and Mansuhk Wani identified the chemical structure of camptothecin. They also identified the chemical structure of taxol, again under the auspices of the NCI. Susan Hoiwitz was contracted by the NCI to elucidate the anticancer mechanisms of camptothecin. She found in the early 1970s that camptothecin induced DNA breaks and attested DNA and RNA synthesis. However, it is approximately 12 years later, only after DNA topo-isomerase I (Topi) had been identified in human cells, that Leroy Liu and his coworkers found that Topi was the cellular target of camptothecin [reviewed in [1]. 

The methylation of deoxyuridine monophosphate (dUMP) to thymidine monophosphate (TMP), catalyzed by thymidylate synthase, is essential for the synthesis of DNA. The one-carbon fragment of methy-lene-tetrahydrofolate is reduced to a methyl group with release of dihydrofolate, which is then reduced back to tetrahydrofolate by dihydrofolate reductase. Thymidylate synthase and dihydrofolate reductase are especially active in tissues with a high rate of cell division. Methotrexate, an analog of 10-methyl-tetrahydrofolate, inhibits dihydrofolate reductase and has been exploited as an anticancer drug. The dihydrofolate reductases of some bacteria and parasites differ from the human enzyme inhibitors of these enzymes can be used as antibacterial drugs, eg, trimethoprim, and anti-malarial drugs, eg, pyrimethamine. 

Entry 5 in Scheme 11.4 is a step in the synthesis of the anticancer drug tamoxifen. Explain why the 2-phenylbutanoyl group is introduced in preference to a trifluoroacetyl group. 

Hambley and co-workers have reported the synthesis, DNA cross-linking, and in vitro anticancer properties of a platinum(II) complex that was designed to bind the macromolecule in an interstrand rather than intrastrand manner,162 the latter being the dominant mode of DNA-binding by platinum anticancer drugs such as cisplatin. The complex [PtCl2(hpip)] ((46) ... 

This chapter has introduced the aldol and related allylation reactions of carbonyl compounds, the allylation of imine compounds, and Mannich-type reactions. Double asymmetric synthesis creates two chiral centers in one step and is regarded as one of the most efficient synthetic strategies in organic synthesis. The aldol and related reactions discussed in this chapter are very important reactions in organic synthesis because the reaction products constitute the backbone of many important antibiotics, anticancer drugs, and other bioactive molecules. Indeed, study of the aldol reaction is still actively pursued in order to improve reaction conditions, enhance stereoselectivity, and widen the scope of applicability of this type of reaction. 

As an example, we present in Exhibit 10.8 the synthesis of paditaxel (Taxol, Bristol-Myers Squibb), an important anticancer drug for breast and ovarian cancer and Kaposi sarcoma. It illustrates the complexity in the synthesis of drug molecules. 

Zerouga M, Stillwell W, Jenski LJ. Synthesis of a novel phosphatidylcholine conjugated to docosahexaenoic acid and methotrexate that inhibits cell proliferation. Anticancer Drugs 2002 13 301. 

Hydroxyurea, an anticancer drug, blocks DNA synthesis indirectly by inhibiting ribonucleotide reductase. 

Pettit GR, Temple C, Narayanan VL, Varma R, Simpson MJ, Boyd MR, Rener GA, Bansal N. (1995) Antineoplastic agents 322. Synthesis of combretastatin A-4 prodrugs. Anticancer Drug Des 10 299-309. 

Baston, E., Klein, C. D., Grimminger, W., Hebecker, N., and Hartmann, R. W. (2001) Synthesis, evaluation and QSAR studies of highly potent aromatase inhibitors of the piperidinedione type. Anticancer Drug Des. 16, 37-47. 

Pouget, C. et al.. Synthesis and structure of flavan-4-ols and 4-methoxyflavans as new potential anticancer drugs. Tetrahedron, 56, 6047, 2000. 

Fig. 10b. A scheme of its synthesis. First, a reactive comonomer. Af-methacryloylglycyl-phenylalanylleucylgycine p-nitrophenyl ester was synthesized. In the second step a polymeric precursor is prepared by copolymerization of the reactive comonomer with A-(2-hydroxyp-ropyl)methacrylamide. After purification and characterization of the polymeric precursor, the anticancer drug (adriamycin) and targeting moiety (galactosamine) are attached by consecutive aminolysis. For details see, e.g., [169]...

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