Complexes cytotoxicity

Mc2Sn(cap) and Et2Sn(cap) do not affect the embryonic development Bu2Sn(cap) and Bu2Sn(cap) exert toxic activity on C. intestinalis embryos in the early stages of development. This toxicity is concentration-dependent and is related to the lipophilic properties of the complexes. Cytotoxic... 

Stratford IJ, Williamson C, Adams GE. Combination studies with misonidazole and a cis-platinum complex cytotoxicity and radiosensitization in vitro. BrJ Cancer 1980 41 517-522. 

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

Epoxides are found in thousands of biological molecules and constitute vital functional entities. They can impart localized structural rigidity, confer cytotoxicity through their role as alkylating agents, or act as reactive intermediates in complex synthetic sequences. The widespread occurrence of epoxides is contrasted by only a handful of aziridines that are known to date. In this chapter we would like to introduce the different mechanisms by which enzymes produce epoxides. 

When induced in macrophages, iNOS produces large amounts of NO which represents a major cytotoxic principle of those cells. Due to its affinity to protein-bound iron, NO can inhibit a number of key enzymes that contain iron in their catalytic centers. These include ribonucleotide reductase (rate-limiting in DNA replication), iron-sulfur cluster-dependent enzymes (complex I and II) involved in mitochondrial electron transport and cis-aconitase in the citric acid cycle. In addition, higher concentrations of NO,... 

Perifascicular capillaries are closer to aggregates of antibody-secreting cells (B-lymphocytes) situated in perimysial connective tissue and therefore are most severely affected by antibody-dependent cytotoxic reactions. Immune-complex deposition occurs at a higher level in the vascular tree (i.e., at arteriolar level) and this may cause fluctuations in perfusion pressure. Perifascicular capillaries are most distal from the head of vascular pressure and therefore most likely to suffer from periodic anoxia. 

In contrast to this view, but in analogy with the behavior of several antitumor metal complexes, some authors proposed that the DNA is the probable target for cytotoxic activity of organotin(IV) compounds. In this section we survey and compare the most important literature data published to date on this subject. 

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. 

Utilizing an alternate mode of Diels-Alder reactivity, Harman has examined the cycloaddition reactions of 4,5-T -Os(II)pentaammine-3-vinylpyrrole complexes with suitably activated dienophiles <96JA7117>. For instance, cycloaddition of the p-vinylpyrrole complex 58 with 4-cyclopentene-l,3-dione, followed by DDQ oxidation affords 59, possessing the fused-ring indole skeleton of the marine cytotoxic agent, herbindole B. 

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