Cytotoxicity of ruthenocene-containing ß-diketones.

BACKGROUND: Ferrocene-containing ß-diketones and cisplatin, [(NH(3))(2)PtCl(2)], possess strong antineoplastic activity. No information is available regarding the anticancer activity of the corresponding ruthenocene complexes. This study examined the cytotoxicity of stable ruthenocene-containing ß-diketones. The results were related to the cytotoxicity of cisplatin and the ease of ruthenium electrochemical oxidation. MATERIALS AND METHODS: The ruthenocene-containing ß-diketones RcCOCH(2)COR where Rc=Ru(II)(C(5)H(5))(C(5)H(4)) and R=CF(3) (1), CH(3) (2), Ph=C(6)H(5) (3) and Fc=Fe(II)(C(5)H(5))(C(5)H(4)) (4) were tested for cytotoxicity against HeLa (human cervix epithelioid) cancer, COR L23 (human large cell lung carcinoma) and the platinum-resistant CoLo 320DM (human colorectal) and COR L23/CPR cancer cell lines. Cell survival was measured by means of the colourimetric 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay. RESULTS: The 50% cell growth inhibition (IC(50)) values of 1-4 towards the cells ranged between 8.2 and 84.6 µmol dm(-3), with 1 being the most cytotoxic complex. Drug activity was directly proportional to the electron density on the ruthenium centre as well as the oxidation potential of the ruthenium core but inversely proportional to the pK(a) of the ß-diketones. The strongest activity was observed against the COR L23 cell line, and the weakest activity against COR L23 CPR. CONCLUSION: A drug activity-structural relationship exists for ruthenocene-containing ß-diketones in that drugs with the lowest electron density on the ruthenium centre are more cytotoxic. Compounds with larger ruthenium oxidation potentials and stronger acid strength (i.e. smaller pK(a) values) are more cytotoxic.

Antiplasmodial and antitumor activity of dihydroartemisinin analogs derived via the aza-Michael addition reaction.

A series of dihydroartemisinin derivatives were synthesized via an aza-Michael addition reaction to a dihydroartemisinin-based acrylate and were evaluated for antiplasmodial and antitumor activity. The target compounds showed excellent antiplasmodial activity, with dihydroartemisinin derivatives 5, 7, 9 and 13 exhibiting IC(50) values of ≤10 nM against both D10 and Dd2 strains of Plasmodium falciparum. Derivative 4d was the most active against the HeLa cancer cell line, with an IC(50) of 0.37 µM and the highest tumor specificity.

Novel N-heterocyclic ylideneamine gold(I) complexes: synthesis, characterisation and screening for antitumour and antimalarial activity.

Ylideneamine functionalised heterocyclic ligands, 1,3-dimethyl-1,3-dihydro-benzimidazol-2-ylideneamine (I), 3-methyl-3H-benzothiazol-2-ylideneamine (II) or 3,4-dimethyl-3H-thiazol-2-ylideneamine (III), were employed in the preparation of a series of both charged and neutral gold(I) complexes consisting either of a Au(C(6)F(5)) fragment (1-3), a [Au(PPh(3))](+) unit (4-6) or a [Au(NHC)](+) unit (7) coordinated to the imine nitrogen of the neutral ylideneamine ligand. These complexes were fully characterised by various techniques including X-ray diffraction. In addition, the antitumour and antimalarial potential of selected compounds were assessed in a preliminary study aimed at determining the medicinal value of such compounds. Complexation of the azol-2-ylideneamine ligands with [Au(PPh(3))](+) increases their antitumour as well as antimalarial activity.