Antineoplastic agent complexes

The antineoplastic agent mitindomide (160) in fact represents the well-known product from irradiation of maleimide in benzene [30]. The activity of this old compound was uncovered by one of the large antitumor screens maintained by the National Cancer Institute, The structure is sufficiently complex and the starting materials sufficiently available to lead one to suspect that the product is still produced photochemically. The product can be rationalized by assuming successive 1,4 and 1,2 additions to benzene. Intermediate 159a involves the 1,4 followed by 1,2 addition intermediate 159b presupposes the steps occur in the reverse order. 

Some tumors are estrogen-dependent and the use of an antiestrogen has therapeutic value. One such antineoplastic agent appears to be patterned after clomiphene. Complex aryl ketone 204 is treated with phenyl magnesium chloride and the resulting tertiary... 

Finally these compounds may also present in the future some interest in the area of novel anti-tumor drugs, or in photochemotherapy [12], Up to now the mechanism of action of the Pt complexes as antineoplastic agents has been extensively examined [13]. In spite of their successful applications, there is a need in compounds that are less toxic than the Pt derivatives. Therefore novel photo-active metallic compounds could offer future possibilities for cancer treatment. The fact that a drug would become active exclusively under illumination might represent an advantage. 

Platinum complexes (e.g., di-platinum, 8.100) are used as antineoplastic agents in the treatment of cancer. Their use is described in chapter 7. 

The derivative 147 of camptothecin 146, naturally occurring antineoplastic agent, stabilizing the enzyme-mediated DNA cleavage, has been tritium-labelled at C,5) position by a three-step sequence starting from 5)-10-hydroxycamptothecin in order to investigate whether the presence of a peripheral electrophilic substituent in 147 renders the reversible binding of 146 with DNA-topoisomerase I covalent complex irreversible . ... 

The effectiveness of transition-metal eomplexes, particularly platinum complexes, as experimental antineoplastic agents has been reported in reeent years. Cisplatin is the prototype platinum complex having antineoplastic activity. 

The drug essentially cross-links DNA and, therefore, behaves like alkylating antineoplastic agents. In general, the platinum complex acts as apotent inhibitor of DNA polymerase. Based on adequate... 

Similar systems contacting ruthenium as active antineoplastic agents has been also proposed. Such complex rappresent and efficient and promising alternative to the platinum anticancer agents. ... 

As Bleomycin A2, B-40 with R = -general references. Minor component of the antibiotic complex Bleomycin, BAN isol. from Streptomyces verticillus. Antineoplastic agent. Log P -11.1 (uncertain value) (calc). 

In the arsenal of anticancer metallodrugs, the coordination complexes of platinum are currently the most commonly used antineoplastic agents as, alone or in association, they are involved in more than 70% of treatments [45-47] The coordination complexes shown in Fig. 42.1 represent some of the most widely used species. 

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