Cytotoxic tests recently performed at National Cancer Institute, NCI (USA), on [Cu(HPIR)(2)(DMF)(2)], 1, (H(2)PIR=
piroxicam, 4-hydroxy-2-methyl-N-pyridin-2-yl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) a widely used non-steroidal anti-inflammatory
drug,
NSAID [see R. Cini, G. Giorgi, A. Cinquantini, C. Rossi, M. Sabat, Inorg. Chem. 29 (1990) 5197-5200, for synthesis and structural characterization, DMF=
dimethylformamide] (NSC #624662) by using a panel of ca. 50 human
cancer cells, showed growth inhibition factor GI(50) values as low as 20microM against several
cancer lines, with an average value 54.4microM. The activity of 1 is larger against
ovarian cancer cells, non-small
lung cancer cells,
melanoma cancer cells, and central nervous system
cancer cells. The widely used anticancer
drug carboplatin (cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)) (
NSC #241240) has average GI(50) value of 102microM. The reactions of
copper(II)-acetate with other
NSAIDs from the oxicam family were tested and crystalline complexes were obtained and characterized.
Isoxicam (H(2)ISO=4-hydroxy-2-methyl-N-(5-methylisoxazol-3-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HISO)(2)].0.5DMF, 2.0.5DMF (DMF=dimethylfomamide). The coordination arrangement is square-planar and the HISO(-)
anions behave as ambi-dentate
chelators via O(
amide),N(
isoxazole) and O(enolate),O(
amide) donors.
Meloxicam (H(2)MEL=4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) produced [Cu(HMEL)(2)(DMF)].0.25H(2)O, 3.0.25H(2)O. The coordination arrangement is square-pyramidal, the equatorial donors being O(
amide),N(
thiazole) from two HMEL(-)
anions and the apical donor being O(DMF). Unexpectedly,
cinnoxicam (HCIN=2-methyl-1,1-dioxido-3-[(pyridin-2-ylamino)carbonyl]-2H-1,2-benzothiazin-4-yl-(3-phenylacrylate)) produced [Cu(MBT)(2)(PPA)(2)] (MBT=3-(methoxycarbonyl)-2-methyl-2H-1,2-benzothiazin-4-olate 1,1-dioxide, PPA=3-phenyl-N-pyridin-2-ylacrylamide).