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A group of 4 organometallic complexes of Rhodium (I) and 1 Iridium(I) was tested for the evaluation of their anti-inflammatory activity on carrageenin paw edema in rats. All the compounds used inhibited the development of paw edema by more than 50% at different dose-levels. The activity of the pyridinalmethylimine derivative [Rh(COD)PMI]+ Cl- had better results than that of [Rh(NBD)PMI]+ Cl- and even more than the dimeric complexes tested. The higher activity of [Ir(COD)Cl]2 as compared with [Rh(COD)Cl]2 suggests that it would be of interest to examine further Iridium(I) complexes, among which [Ir(COD)PMI]+ Cl- could be a good candidate.

A series of alicyclic amine complexes of the cis-Pt(am)2Cl2 type, showed specific antitumour activity against various animal tumours. We have tested these compounds in a number of bacterial systems indicative of their interaction with bacterial DNA.

The examination of the differential effects of two square-planar rhodium(I) complexes on primary tumor growth and on the formation of spontaneous and artificially (i.v. tumor injection) induced lung metastases of MCa mammary carcinoma suggests different mechanisms of action, depending on the chemical characteristics of the compound used. Of the two complexes used, cyclooctadiene(2-pyridinalmethylimine)Rh(I) chloride and cyclooctadiene(2-pyridinalisopropylimine)Rh(I) chloride, the former compound confirmed the antineoplastic action previously shown in the Lewis lung carcinoma model. The activity of this derivative on lung metastasis formation seems to be unrelated to a cytotoxic action for tumor cells localized in the lungs. More likely, it appears that modifications occurring at the primary tumor level, probably different from a tumor-cell-directed lethality, are responsible for the reduction of spontaneous lung metastasis formation observed in treated animals. The hyperplasia of the spleen induced in treated animals seems to suggest that this compound is endowed with properties typical for biological response modifiers.

The effects of square planar rhodium, [RhacacCOD]o and iridium, [IracacCOD]o complexes and of octahedral ruthenium, [cis-RuCl2 (DMSO)4]o complex have been examined in comparison with cis-dichlorodiammino platinum(II) (cis-PDD). The toxicity in BDF1 mice varies widely and decreasing LD50-values, ranging from 0.94 mg/kg to 1000 mg/kg, have been obtained for cis-PDD, [RhacacCOD]o, [IracacCOD]o and [cis-RuCl2(DMSO)4]o, respectively. All the tested complexes similarly inhibit the growth of subcutaneous Lewis lung carcinoma and the development of spontaneous as well as of artificial metastases, with the exception of [IracacCOD]o which is inactive on metastases. The antitumor activity of [RhacacCOD]o and [cis-RuCl2(DMSO)4]o appears interesting, since it is of the same magnitude as that of cis-PDD, considering also that they were found to be only marginally nephrotoxic.

The antitumor action of two square planar Rhodium complexes was tested on MCa mammary carcinoma and was seen to depend upon the compound used. The complex cyclooctadiene(2-pyridinalmethylimine)-Rh(I)chloride [Rh(COD)PMI]+ Cl- confirmed the antineoplastic action already shown in the Lewis lung carcinoma model. The examination of the activity of [Rh(COD)PMI]+ Cl- on the lung metastatic tumor indicates that its antineoplastic properties do not seem simply related to a cytotoxic action. It appears more likely that modifications occurring at the primary tumor level, probably different from lethal effects directed to tumor cells, are responsible for the reduction of spontaneous lung metastasis formation observed in the treated animals. The trophic effects observed on the spleen of the treated animals seem to suggest that these compounds are endowed with properties typical of biological response modifiers.

The effects of a series of pyridinalalkyl-1,5-cyclooctadiene Rhodium(I) complexes were studied on the carrageenin paw edema model, using Sprague-Dawley rats. The series of compounds used were administered at 35, 70 and 140 mumol/kg i.p. 1hr before carrageenin application, and the effect was measured 4hr after carrageenin. The 1,5-cyclooctadienepyridinalaldoxime Rhodium(I) complex proved to be the most active compound, effective also when administered 1hr after carrageenin induction of paw swelling. However, the effects of this complex are not superior to those reported for the methyl derivative, and the overall antiinflammatory activity is inferior to that of this latter compound, particularly when the number of dosages causing at least 80% inhibition are compared. These data are consistent with those obtained in a previous investigation indicating that Rhodium(I) complexes have potential antiinflammatory properties, susceptible of further investigations extended also to other models of inflammatory disease.

The antitumor effects of three rhodium(I) complexes were evaluated using two transplantable tumors of the mouse: Lewis lung carcinoma and P388 lymphocytic leukemia. The examination of the differential effects on primary tumor growth and on the formation of spontaneous pulmonary metastases, in mice bearing Lewis lung carcinoma, indicated that the complex having qualitatively the higher solubility in aqueous solutions and the higher resistance to inactivation via oxidation, displayed the more pronounced antineoplastic activity. The antileukemic effects, in mice bearing P388 lymphocytic leukemia, also seemed to depend on the chemical characteristics of the complex used, and the previously reported trend was particularly evident using an acute treatment performed 24 hr after tumor transplantation.