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Synthesis and cytotoxicity studies of steroid-functionalized titanocenes as potential anticancer drugs: sex steroids as potential vectors for titanocenes

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Abstract

Six titanocenyls functionalized with steroidal esters have been synthesized and characterized by infrared, 1H, and 13C 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.

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Acknowledgments

E.M. acknowledges the NIH-MBRS SCORE Program at the University of Puerto Rico Mayagüez and that at the Ponce School of Medicine for financial support via NIH-MBRS-SCORE Program grants S06 GM008103-36 and S06 GM008239-23 and the PSM-Moffitt Cancer Center Partnership 1U56CA126379-01. In addition, E.M. thanks the NSF-MRI Program for providing funds for the purchase of the 500-MHz NMR instrument.

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Authors and Affiliations

  1. Department of Chemistry, University of Puerto Rico, Mayagüez, PR, 00681, USA

    Li Ming Gao, José L. Vera & Enrique Meléndez

  2. Department of Pharmacology, Toxicology and Physiology, Ponce School of Medicine, Ponce, PR, 00732-7004, USA

    Jaime Matta

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  1. Li Ming Gao
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  2. José L. Vera
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  3. Jaime Matta
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  4. Enrique Meléndez
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Correspondence to Enrique Meléndez.

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Gao, L.M., Vera, J.L., Matta, J. et al. Synthesis and cytotoxicity studies of steroid-functionalized titanocenes as potential anticancer drugs: sex steroids as potential vectors for titanocenes. J Biol Inorg Chem 15, 851–859 (2010). https://doi.org/10.1007/s00775-010-0649-7

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  • DOI: https://doi.org/10.1007/s00775-010-0649-7

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