Antitumor drugs resistance

Keywords Pyrrole Natural products Antitumor agents Multi-drug resistance... 

The vinca alkaloids vinblastine and vincristine are capable of producing the MDR phenotype in a wide variety of cell types. Furthermore, cells that are made resistant to antitumor drugs such as doxorubicin, actinomy-cin D, or the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26) are often resistant to the effects of the bisindole alkaloids. The structural and mechanistic diversity of these compounds is even more striking against the backdrop of collateral resistance. 

Graham CH, Kobayashi H, Stankiewicz KS, Man S, Kapitain SJ, Kerbel RS (1994) Rapid acqisition of multicellular drug resistance after a single exposure of mammary tumor cells to antitumor aklylating agents. J Natl Cancer Inst 86 975-982... 

Killion JJ, Beltran P, O Brian CA, Yoon SS, Fan D, Wilson MR, Fidler IJ (1995) The antitumor activity of doxorubicin aganist drug-resistant murine cardnom is enhanced by oral administration of a synthetic staurosporine analogue, CGP 41251. Oncol Res 7 453-459... 

Antitumor drugs cisplatin as, history, 37 175-179 platinum compounds future studies, 37 206-208 resistance to, 37 192-193 second-generation, 37 178 Antiviral agents, 36 37-38 AOR, see Aldehyde oxidoreductase Aphanothece sacrum, ferredoxins, amino acid sequence, 38 225-227 Apo-calcylin, 46 455 Apo-caldodulin, 46 449-450 Apoenzyme, 22 424 Apoferritin biosynthesis, 36 457 cystalline iron core, 36 423 Fe(III)distribution, 36 458-459 Fe(II) sequestration, 36 463-464 ferroxidase centers, 36 457-458 iron core reconstruction in shell, 36 457 mineralization, 36 25 Mdssbauer spectra, 36 459-460 optical absorbance spectra, 36 418-419 subunit conformation and quaternary structure, 36 470-471... 

Anthracyclines are antitumor quinone containing antibiotics produced by different strains of Streptomyces. Some of them, such as adriamycin doxorubicin), and daunorubicin are broad spectrum antitumor compounds. They act by binding to DNA and interfering with DNA replication and gene transcription. Their limitations for clinical use are cardiac toxicity and drug resistance phenomena. Consequently, intense structure-activity relationship studies have been performed to improve the pharmacological profile as well as to enhance the affinity for DNA. In particular, a number of fluorinated anthracyclines have been prepared with introduction of fluorine atoms into D or A cycles, and into the aglycone side chain linked atC-14. ... 

Transition-metal based compounds constitute a discrete class of chemotherapeutics, widely used in medicine as antitumor agents.56 Several ruthenium complexes enable the body to catalyze oxidation and reduction reactions, depending on the physiological environment, and have attracted much interest as alternative antitumor drugs in the treatment of cancer cells resistant to cisplatin in cancer... 

There is another important aspect of DNA damages. A unique feature of many cancerous tumors is the existence of hypoxic regions, that is, regions of oxygen-poor cells (J.M. Brown 1999). Such cells are often resistant to more conventional forms of antitumor treatment, such as radiotherapy and chemotherapy (Denny Wilson 2000). There has been considerable effort to identify potential antitumor drugs that specifically target such cells. One such class of potential hypoxia-specific drugs is the benzotriazine A, A -dioxides, of... 

Brabec V, Kasparkova J. Modifications of DNA by platinum complexes. Relation to resistance of tumors to platinum antitumor drugs. Drug Resist Update. 2005 8 131-146. 

Table 4. Cytotoxicity of Selected Antitumor Agents Against Ovarian and Drug-Resistant Ovarian Cancer Cell Lines (IC50 nM)a...

Welwistatin also inhibits cell proliferation with reversible depletion of cellular microtubules in ovarian carcinoma cells and A-10 vascular smooth muscle cells by inhibiting the polymerization of tubulin, but it does not alter the ability of tubulin to bind [3H]colchicine or to hydrolyze GTP [8]. Due to the cytotoxicity associated with the inhibition of tubulin polymerization, which is the main mechanism of action of antitumor drugs such as vincristine and vinblastine, and because P-gp-overexpressing cells show virtually no resistance to welwistatin due to its MDR reversal properties, this natural product could be a good candidate in the chemotherapy of drug-resistant tumors. 

Vock CA, Ang WH, Scolaro C, Phillips AD, Lagopoulos L, Juillerat-Jeanneret L, Sava G, Scopelliti R, Dyson PJ (2007) Development of ruthenium antitumor drugs that overcome multidrug resistance mechanisms. J Med Chem 50 2166-2175... 

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