Genotoxicity of Some Metal-Based Antineoplastics, Evaluated by SOS Chromotest and Cytogenetic Analysis.

The paper reports the screening results of two metal-based antineoplastic drugs with mutagenic potential, such as Romcis (trademark of Cisplatinum, produced in Romania) and diphenylantimony(III) diisopropyldithiophosphate (PADTF). Their effects were compared with those induced by Cyclophosphamide. Two mutagenicity tests, the SOS Chromotest and cytogenetic analysis were applied. The tests were carried out with or without metabolic activation (addition of S(9)-mix), either in E. coli PQ 37 cultures, using four doses (0.3, 3, 30 and 300 pmol compound/assay) for the SOS Chromotest or in leukocyte cultures using 0.3 mM from each compound, for cytogenetics. The dose- response relationships and SOSIP values revealed an indirect mutagenic potential for Cyclophosphamide, amplified by S(9) mix in bacterial cultures and an antiproliferative, clastogenic effect on lymphocytes. For Romcis and diphenylantimony(III) diisopropyldithiophosphate, a significant positive response by SOS Chromotest was recorded, which correlated with increased frequencies of chromosomal aberrations.

Antitumour Organometallics. III. In Vivo Activity of Diphenylantimony(III) and Diorganotin(IV) Dithiophosphorus Derivatives Against P388 Leukemia.

Diphenylantimony(III) and diorganotin(IV) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PR'(2) (R' = Ph, OPr-i) and R(2)Sn(S(2)PR'(2))(2) (R = n-Bu, Ph, R' = Ph; R = Ph, R' = OPr-i), have been screened against P388 leukemia in mice. All the compounds showed marginal activity towards this tumor system, some of them increasing the life span of the animals with more than 20%. The best results were obtained with (di-iso-propylphosphorodithioato)diphenylantimony(III) which exhibited a T/C value of 136%, at a dose of 5 mg/kg, administered on days 1,2 and 3 after tumor transplantation.

Antitumor Organometallics. IV. The Mutagenic Potential of Some Diphenylantimony(III) Dithiophosphorus Derivatives.

Two diphenylantimony(III) derivatives of dithiophosphorus ligands, i.e. Ph(2)SbS(2)PPh(2) and Ph(2)SbS(2)P(OPr-i)(2), which were previously found to exhibit antitumor properties, have been now investigated for potential mutagenic effects in healthy and Ehrlich ascites tumor-bearing mice. Two short-term tests, i.e. the micronucleus test and the cytogenetic analysis, were used as end-points for mutagenicity. The results are consistent with a mutagenic potential for both organoantimony(III) compounds tested, the effect being higher for the phosphorodithioato derivative.

Antitumor organometallics. I. Activity of some diphenyltin(IV) and diphenylantimony(III) derivatives on in vitro and in vivo Ehrlich ascites tumor.

Diphenyltin(IV) and diphenylantimony(III) derivatives of dithiophosphorus ligands, i.e. Ph2Sn(S2PPh2)2 (1), Ph2Sn[S2P(OPr)2]2 (2), Ph2SbS2PPh2 (3) and Ph2SbS2P(OPri)2 (4), have been tested in vitro and in vivo against Ehrlich ascites tumor. All four compounds were almost equally effective in vitro, exhibiting inhibitory effects on cell proliferation, viability and protein synthesis, and exacerbated respiration and Ca-ATPase activity. In mice bearing Ehrlich ascites tumor cells, all four compounds inhibited the tumor growth, the organometallic phosphorodithioates being more active than phosphinodithioate analogues, and the organoantimony derivatives more active than organotins. Compound 4 (5 mg/kg/day, i.p., on days 1,3 and 5) produced an increase in life span of 83% and a cure rate of 30% in mice bearing this tumor.

Antitumor organometallics. II. Inhibitory effects of two diphenyl-antimony (III) dithiophosphorus derivatives on in vitro and in vivo Ehrlich ascites tumor.

(Diphenylphosphinodithioato) diphenylantimony (III), Ph2SbS2PPh2 (1) and (diisopropylphosphorodithioato) diphenylantimony(III), Ph2SbS2P(OPri)2 (2) were tested in vivo in male AKR mice and in vitro against Ehrlich ascites tumor cells. Both compounds exhibited dose-dependent inhibitory effects on in vivo tumor growth and on in vitro cell proliferation, cell viability, respiration and protein synthesis. The activities of some enzymes involved in energetic metabolism (Ca-ATPase, LDH, G6Pase) were exacerbated in vitro. The inhibitory effects could be related to the imbalance between ATP-producing and ATP-consuming processes in Ehrlich ascites tumor cells and also to their cell-cycle specificities.

The first organoantimony(III) compounds possessing antitumor properties: diphenylantimony(III) derivatives of dithiophosphorus ligands.

Two organoantimony (III) derivatives, i.e., diphenylantimony diphenyl-dithiophosphinate, Ph2SbS2PPh2, and diphenylantimony diizopropyldithiophosphate, Ph2SbS2P(OPri)2, were shown to exhibit antitumor properties. Both compounds produced strong tumor inhibition effects in mice bearing Ehrlich ascites tumor. Moreover, the dithiophosphate (15 mg/kg, i.p., in days 1, 3 and 5) produced a cure rate of 30%.

Rhodium, iridium, copper and gold antitumor organometallic compounds (review).

Recent results on the antitumor activity of organometallic compounds of rhodium, iridium, copper and gold are reviewed. Coordination compounds of some organic ligands are also briefly mentioned. The most promising seem to be copper and gold complexes which exhibited remarkable activity against several tumor systems.