Anticancer activity of dinuclear gallium(III) carboxylate complexes

• Published in: European journal of medicinal chemistry Vol. 45; no. 2; pp. 519 - 525
• Main Authors: KALUDEROVIC, Milena R, GOMEZ-RUIZ, Santiago, GALLEGO, Beatriz, HEY-HAWKINS, Evamarie, PASCHKE, Reinhard, KALUDEROVIC, Goran N
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier 01.02.2010
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Carboxylic Acids - chemistry; Cell Line, Tumor; Cell Survival - drug effects; Gallium - chemistry; General aspects; Humans; Inhibitory Concentration 50; Medical sciences; Models, Molecular; Molecular Conformation; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Pharmacology. Drug treatments; Spectrum Analysis; Antineoplastic agent; Human; Gallium; Carboxylato ligands; Gallium Organic compounds; Organic ligand; Anticancer drugs; Cytotoxicity; Gallium III Complexes; Transition metal Complexes; Trivalent metal Complexes; In vitro; Cisplatin; Mu complex; Cell line; Structure activity relation; Carboxylate; Dinuclear complex; Chemical synthesis; Tumor cell
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.10.038

The reaction of 3-methoxyphenylacetic acid, 4-methoxyphenylacetic acid, mesitylthioacetic acid, 2,5-dimethyl-3-furoic acid and 1,4-benzodioxane-6-carboxylic acid with trimethylgallium (1:1) yielded the dimeric complexes [Me(2)Ga(micro-O(2)CCH(2)C(6)H(4)-3-OMe)](2) (1), [Me(2)Ga(micro-O(2)CCH(2)C(6)H(4)-4-OMe)](2) (2), [Me(2)Ga(micro-O(2)CCH(2)SMes)](2) (3) (Mes=2,4,6-Me(3)C(6)H(2)), [Me(2)Ga{micro-O(2)C(Fur)}](2) (4) (Fur=2,5-dimethylfuran) and [Me(2)Ga{micro-O(2)C(Bdo)}](2) (5) (Bdo=1,4-benzodioxane) respectively. The molecular structure of 5 was determined by X-ray diffraction studies. The cytotoxic activity of the gallium(III) complexes (1-5) was tested against human tumor cell lines 8505C anaplastic thyroid cancer, A253 head and neck tumor, A549 lung carcinoma, A2780 ovarian cancer, DLD-1 colon carcinoma and compared with that of cisplatin. Taking into account the standard deviation, there is no significant difference in the activity for any of the compounds in any cell line. However, complex 5 presents the best IC(50) value against A253 head and neck tumor (6.6+/-0.2 microM), while complex 3 seems to be the most active against A2780 ovarian cancer (12.0+/-0.4 microM) and marginally on DLD-1 colon carcinoma (12.4+/-0.1 microM).