Synthesis and cytotoxicity studies of steroid-functionalized titanocenes as potential anticancer drugs: sex steroids as potential vectors for titanocenes.
Six titanocenyls functionalized with steroidal esters have been synthesized and characterized by infrared, (1)H, and (13)C NMR spectroscopy and elemental analysis. Among those steroids, dehydroepiandrosterone, trans-androsterone, and androsterone are androgens and pregnenolone is a progesterone precursor. Clionasterol is a natural steroid compound. These steroid-functionalized titanocenyls were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for in vitro cytotoxicity for MCF-7 breast cancer and HT-29 colon cancer cells. All complexes exhibited more cytotoxicity than titanocene dichloride. The titanocenyls containing androgen and progesterone derivatives as pendant groups had higher antiproliferative activities than those with cholesterol steroid compounds. Of particular significance is titanocenyl-dehydroepiandrosterone complex, which is 2 orders of magnitude more cytotoxic than titanocene dichloride and also shows much more sensitivity and selectivity for the MCF-7 cell line.
Gao
Li Ming
LM
Department of Chemistry, University of Puerto Rico, Mayagüez, PR 00681, USA.
Vera
José L
JL
Matta
Jaime
J
Meléndez
Enrique
E
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D012739:Gonadal Steroid Hormones / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D011789:Quantum Theory; D013057:Spectrum Analysis; D013256:Steroids / Q000737:chemistry*
D000970:Antineoplastic Agents; D012739:Gonadal Steroid Hormones; D009942:Organometallic Compounds; D013256:Steroids; C406884:titanocene