Anticancer activities

IM PDH. At doses as high as 100 jjlM, 62 did not show in vitro growth inhibition effects against cancer cells in the NCI s disease-oriented screening program [58], 

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Many other bisben2ylisoquinoliae alkaloids, such as tetrandriae (80), from Cjcleapeltata Hook., are also known. Compound (80), for example, although it causes hypotension and hepatotoxicity ia mammals, ia other tests, possessed enough anticancer activity to be considered for preclioical evaluation (55). The arrow poison tubocurare prepared from Chondrendendron spp. also contains the bisben2yhsoquiQoline alkaloid tubocurariae (9). 

Quinones of various degrees of complexity have antibiotic, antimicrobial, and anticancer activities, eg, a2iddinornitosene [80954-63-8] (36), (-)-2-methyl-l,4-naphthoquinone 2,3-epoxide [61840-91 -3] (37), and doxombicin [23214-92-8] (adriamycin) (38) (see Antibiotics Chemotherapeutics, anticancer), ah of these natural and synthetic materials have stimulated extensive research in synthetic chemistry. 

Thiatriazole, 5-arylamino-alkylation, 6, 596 anticancer activity, 6, 598 methylation, 6, 590 reactions... 

For example, treatment of dione 12 with hydrochloric acid yielded furan 13, a key synthetic intermediate for the production of a variety of compounds that were recently investigated for anticancer activity. Related inquiries by members of the same research team identified furans derived from IS as potential treatments for RNA viruses. Furan IS was prepared by condensation of dione 14 with catalytic sulfuric acid in refluxing acetic anhydride. ... 

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]. 

This survey of the literature data on the interactions of organotin(IV) cations with biologically active ligands demonstrates that this is still a very open field. Above all, it is necessary to emphasize that usage of such complexes to treat humans is not permitted at present. Consequently, all compounds examined and discussed here (although with promising anticancer activity) are in the exploratory research stage. 

The anticancer activity of complex natural products having a cyclodecenediyne system [for a review see <96MI93>] has prompted the synthesis of 54 (X = CH2 and OCH2) <96CC749> and 55 (R = a-OH and p-OH) <95AG(E)2393> on the basis that such compounds are expected to develop anticancer activity as the P-lactam ring opens. This is because cycloaromatization can only occur in the monocyclic enediyne and the diradical intermediate in the cyclization is thought to be the cytotoxic species. 

Some 1,2,4-triazines having a 1,2,4-triazinone substituent, and some 1,2,4-triazolo[4,3-fc]-1,2,4-triazinones have been shown to have in vitro anti-HIV and anticancer activity < 95MI04 96CA(124)86961 >. 

Wang X, Wei Y, Yuan S, Liu G, Lu Y, Zhang J, et al. Potential anticancer activity of tanshinone IIA against human breast cancer. IntJ Cancer 2005. 

As 2-amino-2-deoxy-D-mannose is tumorstatic and 2-acetamido-2-deoxy-D-mannose 6-phosphate is an obligatory intermediate in the biosynthetic pathway to sialic acid, displacement of the essential OH-6 with a fluorine atom should be interesting from the biological viewpoint. 2-Acetamido-1,3,4-tri-0-acetyl-2,6-dideoxy-6-fluoro-D-mannopyranose (see Table 111 in Section 11,3) and its O- and A,0-deacetyl derivatives were prepared the first compound showed weak anticancer activity. 

Bomser, J. et al., In vitro anticancer activity of fruit extracts from Vaccinium species, Planta Med, 62, 212, 1996. 

Etoposide (XV) is a semisynthetic gylcoside derivative of podophyllotoxin, which is one of the most extensively used anticancer drugs in the treatment of various types of tumors [64,65]. The anticancer activity of this drug is mainly due to its ability to inhibit an ubiquitous and essential enzyme human DNA topo II [66,67]. Despite its extensive use in the treatment of cancers, it has several limitations, such as poor water solubility, drug resistance, metabolic inactivation, myelosuppression, and toxicity [68]. In order to overcome these... 

This reaction has been used in the synthesis of a portion of callipeltoside, a substance with anticancer activity. 

Entries 4 and 5 are examples of use of the Sakurai reaction to couple major fragments in multistage synthesis. In Entry 4 an unusual catalyst, a chiral acyloxyboronate (see p. 126) was used to effect an enantioselective coupling. (See p. 847 for another application of this catalyst.) Entry 5 was used in the construction of amphidinolide P, a compound with anticancer activity. 

Altretamine, formerly known as hexamethylmelamine, is similar in structure to alkylating agents but is known to have anticancer activity in cancer cells resistant to alkylating agents. Altretamine is well absorbed after oral administration and undergoes rapid and extensive demethylation in the liver. Peak plasma concentrations were observed 0.5 to 3 hours after administration. The terminal half-life is 4.7 to 10.2 hours. 

Platinum(IV) complexes have been known to be anticancer active since the original studies in this area by Rosenberg.447 Consequently numerous platinum(IV) complexes have been prepared for biological testing. Until recently, the great bulk of these were trans-dihydroxo complexes prepared... 

The anticancer activity of platinum(IV) complexes, and the belief that reduction is needed to initiate this activity, had generated substantial interest in the rates and mechanism of reduction by biologically relevant reductants such as thiols, ascorbic acid, and methionine. Reduction of platinum(IV) to platinum(II) usually proceeds as a single two-electron step and is usually first-order with respect to both platinum(IV) and reductant concentrations. 

Berger, I., Hanif, M., Nazarov, A. A., Hartinger, C. G., John, R. O. Kuznetsov, M. L. et al. In Vitro Anticancer Activity and Biologically Relevant Metabolization of Organometallic Ruthenium Complexes with Carbohydrate-Based Ligands. Chemistry Europ. Journal 14, 9046-9057 (2008). 

Sharoni, Y., Danilenko, M., Walfisch, S. et al. 2002. Role of gene regulation in the anticancer activity of carotenoids. PureAppl Chem 74 1469-1477. 

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