Cytotoxic studies of substituted titanocene and ansa-titanocene anticancer drugs.
A variety of substituted titanocene and ansa-titanocene complexes have been synthesized and characterized using traditional methods. The cytotoxic activity of the different titanocene complexes was tested against tumour cell lines human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x and normal immunocompetent cells, peripheral blood mononuclear cells PBMC. Alkenyl substitution, either on the cyclopentadienyl ring or on the silicon-atom ansa-bridge of the titanocene compounds [Ti{Me(2)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(3){CMe(2)CH(2)CH(2)CHCH(2)})}Cl(2)] (8), [Ti{Me(CH(2)CH)Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] (9) and [Ti(eta(5)-C(5)H(4){CMe(2)CH(2)CH(2)CHCH(2)})(2)Cl(2)] (12) showed higher cytotoxic activities (IC(50) values from 24+/-3 to 151+/-10 microM) relative to complexes bearing an additional alkenyl-substituted silyl substituent on the silicon bridge [Ti{Me{(CH(2)CH)Me(2)SiCH(2)CH(2)}Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] (10) and [Ti{Me{(CH(2)CH)(3)SiCH(2)CH(2)}Si(eta(5)-C(5)Me(4))(eta(5)-C(5)H(4))}Cl(2)] (11) which causes a dramatic decrease of the cytotoxicity (IC(50) values from 155+/-9 to >200 microM). In addition, the synthesis of the analogous niobocene complex [Nb(eta(5)-C(5)H(4){CMe(2)CH(2)CH(2)CH=CH(2)})(2)Cl(2)] (13), is described. Structural studies based on DFT calculations of the most active complexes 8, 9 and 12 and the X-ray crystal structure of 13 are reported.
Gómez-Ruiz
Santiago
S
Departamento de Química Inorgánica y Analítica, ESCET, Universidad Rey Juan Carlos, 28933 Móstoles, Madrid, Spain. santiago.gomez@urjc.es
Kaluderović
Goran N
GN
Prashar
Sanjiv
S
Polo-Cerón
Dorian
D
Fajardo
Mariano
M
Zizak
Zeljko
Z
Sabo
Tibor J
TJ
Juranić
Zorica D
ZD
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C406884:titanocene