Antitumor drugs second-generation

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... 

In fact, the very recent 195Pt NMR results of Bancroft et al. (41) indicate that, in agreement with Miller and House (36c), most likely [cis-Pt(NH3)2Cl(H20)]+ is the predominant species that reacts with biomolecules (at least with DNA). Other Pt amine compounds that are antitumor active have different kinetics of the hydrolysis reactions, and usually react much slower. The second-generation drug CBDCA (Fig. 2) is known to hydrolyze (in a 1 mAf solution) with a half-life at 37°C of a few days (41a) (compared to only 1 hour for cis-Pt). 

Ojima, I., Slater, J. C., Michaud, E., et al. (1996) Syntheses and structure-activity relationships of the second generation antitumor taxoids. Exceptional activity against drug-resistant cancer cells. Journal of Medicinal Chemistry, 39, 3889-3896. 

Fig. 4 A second generation of the drug loading micelle with a pH-sensitive drug releasing property, a Formation of pH-sensitive polymeric micelles from PEG-(PAsp-Hyd-Dox) block copolymers. Antitumor drugs (Dox), conjugated through acid-labile hydrazone linkers, are released in lower pH conditions, b Time- and pH-dependent Dox release profile from the micelles. The micelles selectively release Dox under the pH condition of region B, which corresponds to the intracellular environment. The amount of loaded Dox in the micelles was calculated from the released Dox at pH 3.0 where all of the loaded drugs were assumed to be released from the micelle...

Ojima I, Slater JC, Michaud E, Kuduk SC, Bounaud P-Y, Vrignaud P, Bissery M-C, Veith JM, Pera P, Bemacki RJ (1996) Syntheses and Structure-Activity Relationships of the Second-Generation Antitumor Taxoids Exceptional Activity against Drug-Resistant Cancer Cells. J Med Chem 39 3889... 

Figure 1.12 Second-generation antitumor drug candidates having novel chemo-types, which act on mitochondrial voltage-dependent anion channels.

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