Antitumor activity dithiocarbamates

The in vitro trypanocidal and antitumor activities of lfr(cot)L], cot = cyclotetraene, derivatives of dithiocarbamates and xanthates, have been investigated.700 The Ir complexes were characterized by IR spectroscopy, and MO calculations (Hiickel) were performed on the ligands. Similar studies were performed on [Ir(nbr)L], nbr = norbornadiene, L = derivatives of alquil and aryl xanthates 701 and also on [Ir2(cod)2L]X2, where L = 2-hydroxystilbamidine, X = C1, N03, C104, BPh4, and [Ir(cod)L2 ]X, where L = benznidazole, R0-2516, nifurtimox, niridazole. The complex [Ir2(cod)2(2-hydroxystilbami-dine)](BPh4)2 showed the highest activity, as studied by optical microscopy of rats kidneys. 

There are some serious drawbacks to the use of cis-platin in anticancer therapy. Severe toxicity problems occur, such as failure of the kidneys and bone marrow (nephrotoxicity and hematoxicity), nausea, intractable vomiting (emesis), peripheral neuropathy, deafness (ototoxicity), and seizures. These toxic side effects of cisplatin limit the dose that can be administered to patients typical doses are 100 mg day for up to five consecutive days. The nephrotoxicity can be reduced by hydration and diuresis. 5-HT3-receptor blockers control nausea and emesis. Much effort has been devoted to the development of chemopro-tective agents, which alleviate the side effects on normal tissues without compromising antitumor activity - mainly sulfur-containing agents such as sodium dithiocarbamate (Naddtc), 2-mercaptoethanesulphonate (mesna), and amifos-tine (WR-2721). Amifostine has recently been approved for coadministration with cisplatin, which reduces nephro- and neurotoxicity. ... 

Dithiocarbamate 386a and dithiocarbonate 386b show activity against Mycobacterium tuberculosis and antitumor activity [118]. 

Bis(dithiocarbamate) complexes, [M(S2CNC4HgX)2] (M = Pd, Pt X = O, S, CH2), have been tested for cyclostatic activity on KB cells, but show low activity at best (1585), as do a range of cationic amine complexes (1609). In contrast, related diamine complexes [M(diamine)(S2CNR2)][N03] (diamine = 2,2 -bpy, 1,10-phen) show antitumor activity against leucemic cells (1628,1629,1657). Further, administration of various dithiocarbamates at a low dose level with cisplatin has been found to afford almost complete protection against cisplatin induced renal toxicity and body weight loss without... 

Gold dithiocarbamate derivatives as potential antineoplastic agents Design, spectroscopic properties, and in vitro antitumor activity, L. Ronconi, L. Giovagnini, C. Marzano, et al., Inorg. Chem., 2005, 44, 1867. 

The in vivo antitumor and trypanocidal effects of dimeric [Irn2(CH3COO)4(L)ra]° (L = classical organic antimalarial drugs, n= 1, 2) are reported.494 The dimeric complexes are characterized by IR spectroscopy. Further studies of monomeric Ir11 complexes, IrnL2, where L = alkyl or aryl dithiocarbamates and xanthates, reveal no clear relation between antitumor and antitrypanosomal actvities.495 Structure-activity data for the Ir11 complexes is presented. 

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