boron clusters as ligands

In recent years, the pharmaceutical use of metal-based compounds has attracted tremendous attention due to their unique biological potential. Specifically, a large spectrum of biological functionalities that do not occur naturally now become available and provide a broader range of capabilities. Such examples include luminescence, MRI, and PET, among others. When metal ions are combined with inorganic or organic ligands, those possibilities can increase. Moreover, the resulting metal-based compounds can lead to improved pharmacokinetic properties, toxicity, or bioavailability; compared to parental compounds.[1]

After platinum, gallium is considered to be the second most used metal in clinical practice for treating hypercalcemia associated with metastasis in bones. However, its renal toxicity and poor bioavailability are limiting factors for its use.[2] Thus, a new generation of therapeutics was explored to replace simple inorganic salts. For example, gallium maltolate (GM) shows greater cytotoxicity than gallium nitrate in lymphoma cell lines.[3] This work revealed that GM inhibits the growth of lymphoma cells that are resistant to gallium nitrate and can also inhibit the growth of human T-cell lymphoma xenografts in mice (both in vitro and in vivo antitumor activity). Another study showed the high antitumor activity of clinically tested KP46 analog with cloxiquine, which also shows the high level of selectivity toward cancer over noncancerous cells.[4] Mechanistic studies revealed that KP46 is highly potent against osteosarcoma (prevalent bone tumor, current treatments comprise an aggressive combinational therapy of chemotherapy, radiation, and surgery, and poor prognosis when metastasis already occurred[5]) cell lines by inducing cancer cell death and inhibiting their migratory potential.[6]


[1]      a) Haas, K. L., K. J. Franz, Chem. Rev. 2009, 109, 4921; b) Orvig, C., M. J. Abrams, Chem. Rev. 1999, 99, 2201.

[2]      Rudnev, A. V., L. S. Foteeva, C. Kowol, R. Berger, M. A. Jakupec, V. B. Arion, A. R. Timerbaev, B. K. Keppler, J. Inorg. Chem. 2006, 100, 1819.

[3]      Chitambar, C. R., M. M. Al-Gizawiy, H. S. Alhajala, K. R. Pechman, J. P. Wereley, R. Wujek, P. A. Clark, J. S. Kuo, W. E. Antholine, K. M. Schmainda, Mol. Cancer Ther. 2018, 17, 1240.

[4]      Litecká, M., M. Hreusová, J. Kašpárková, R. Gyepes, R. Smolková, J. Obuch, T. David, I. Potočňák, Bioorganic Med. Chem. Let. 2020, 30, 127206.

[5]      Robin, P., K. Singh, K. Suntharalingam, Chem. Commun. 2020, 56, 1509.

[6]      Kubista, B., T. Schoefl, L. Mayr, S. Van Schoonhoven, P. Heffeter, R. Windhager, B. K. Keppler, W. Berger, J. Exp. Clin. Cancer Res. 2017, 36, 1.

[7]      a) Yang, C.-T., S. G. Sreerama, W.-Y. Hsieh, S. Liu, Inorg. Chem. 2008, 47, 2719; b) Holub, J., M. Meckel, V. Kubicek, F. Rosch, P. Hermann, Contrast Media Mol. Imaging 2015, 10, 122.

[8]      Amatori, S., G. Ambrosi, M. Fanelli, M. Formica, V. Fusi, L. Giorgi, E. Macedi, M. Micheloni, P. Paoli, R. Pontellini, P. Rossi, J. Org. Chem. 2012, 77, 2207.