Cytotoxic complexes

Abbate, F., Orioli, P., Bruni, B., Marcon, G. and Messori, L. (2000) Crystal structure and solution chemistry of the cytotoxic complex 1,2-dichloro(o-phenanthroline) gold(III) chloride. Inorganica Chimica Acta, 311, 1. 

Cathcart, M.K., McNally, A.K. and Chisolm, G.M. (1991). Lipoxygenase mediated transformation of human low density lipoprotein to an oxidised and cytotoxic complex. J. Lipid Res. 32, 63-70. 

Stirpe, F., Olsnes, S., and Pihl, A. (1980) Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization, and preparation of cytotoxic complexes with concanavahin A./. Biol. Chem. 255, 6947-6953. 

The lutetium complex 57 is currently under clinical evaluation as a photosensitizer for the treatment of cancer. This complex possesses a strong broad absorption band centered at 732 nm (247). Upon absorption of light, 57 becomes activated to a long-lived triplet state and reacts with 302 to generate cytotoxic. Complex 57 is also on clinical trial as a photosensitizer for the treatment of atherosclerisis, a vascular disease caused by deposition of cholesterol and other fatty materials in the walls of blood vessels. 

ERa, minus the cytotoxic component observed on the ER-negative cancer cells. At a concentration of 1 pM, only the most cytotoxic complexes 4 and 5 are able to overpower the oestrogenic effect of these compounds. Complexes 7 and 8, which are the least cytotoxic on the MDA-MB-231 cells, show a clear proliferative effect. Compound 9 strikes a perfect balance between oestrogenic and cytotoxic effects and shows no overall effect on the MCF-7 cells at 1 pM. 

Dihematoporphyrin derivatives (DHPD) have been introduced in tumor therapy [201]. These derivatives develop high cytotoxicity in light-sensitized cells. Although structurally, the active component appears to be a dimer [202], some suggest it to be the ester [203], and others the ether and the ester [204], it is clear that the cytotoxic complexation occurs via exciplex-ation [42]. Several other esters (mesochlorine and bonellin) of DHPD ether are claimed [205] to be five times more lethal than DHPD. 

D-MS GT oligomers Human Basic isoform of eEFlA IDed in lymphocytes GT oligomer cytotoxicity complex... 

Cytotoxicity is a necessary, but not sufficient criterion for anti-tumour activity. All of the compounds with strong anti-tumour activity in vivo also have potent cytotoxicity when measured against B16 melanoma in vitro. The converse relationship was not observed, as some highly cytotoxic complexes have limited in vivo efficacy. This relationship demonstrates the importance of in vivo metabolism and animal testing in drug design and development. 

Padie C, Maszewska M, Majchtzak K, Nawrot B, Caminade AM, Majraal JP (2009) Polycationic phosphoms dendrimers synthesis, characterization, study of cytotoxicity, complexation of DNA, and transfection experiments. New J Chem 33 318-326... 

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. 

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... 

---