Search for content and authors

New calcipotriol analogs, their toxicity and antitumor activity in vivo in comparison to the affinity with VDR and DBP

Marzena Pełczyńska 1Beata Filip-Psurska 2Magdalena Milczarek 2Janina Kuduk-Jaworska 3Andrzej Kutner 4Joanna Wietrzyk 2

1. Karkonosze College, Higher Professional State School, Lwówecka 18, Jelenia Góra 58-503, Poland
2. Polish Academy of Sciences, Institute of Immunology and Experimental Therapy (IITD), Rudolfa Weigla 12, Wrocław 53-114, Poland
3. Wrocław University, Faculty of Chemistry, 14 F. Joliot-Curie, Wrocław 50-383, Poland
4. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland


Calcitriol, [1α,25-dihydroxyvitamin D3], the seco-steroid hormone, has been proven to be a potent antiproliferative agent against various normal and neoplastic cells. Moreover, calcitriol and other vitamin D analogs revealed the ability to induce differentiation of many human cancer cells. Biological activity of these compounds is mediated by the nuclear vitamin D receptor (nVDR). Calcitriol is carried with plasma Vitamin D Binding Protein (DBP). The affinity with DBP could be responsible for the toxicity and bioavailability. Such biological properties suggest the potential therapeutic application for these agents, including antitumor therapy. The undesired hypercalcemia after calcitriol application which is a serious limitation to its clinical use, explains the motivation to develop new analogs. Two of the promising calcipotriol analogs: PRI-2202, PRI-2205 and the paternal compound have been the objects of our intensive studies. In this work, we present results of the affinity of different analogs of vitamin D with Vitamin D Receptor (VDR) or with Vitamin D binding Protein (DBP) using Molecular Operating Environment (MOE) program. PRI-2205 analog exhibited the highest affinity with VDR and DBP. Furthermore, the toxicity, calcemic activity and antitumor activity of these analogs in the LLC mice tumor model were tested. PRI-2205 analog exhibitad both the low toxicity and calcemic activity and the highest antitumor activity with comparison to other derivatives [1,2].

In conclusion,based on these results, we could formulate the hypothesis about the positive correlation between the antitumor activity of new calcioptriol analog and its affinity with VDR. Moreover, its lower toxicity and calcemic activity seems to be correlated with its higher affinity with DBP.

The authors are grateful to Chemical Computing Group Inc for making the MOE program available for free testing work.

[1] Wietrzyk J., Chodyński M., Fitak H., Wojdat E., Kutner A., Opolski A.: Antitumor properties of diastereomeric and geometric analogs of vitamin D3. Anticancer Drugs, 18(4):447-57, 2007.
[2] Wietrzyk J., Nevozhay D., Filip B., Milczarek M., Kutner A.: The antitumor effect of lowered doses of cytostatics combined with new analogs of vitamin D in mice. Anticancer Res. 27: 3387-3398 2007.


Legal notice
  • Legal notice:

Related papers

Presentation: Poster at VI Multidyscyplinarna Konferencja Nauki o Leku, by Magdalena Milczarek
See On-line Journal of VI Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2008-03-13 16:54
Revised:   2009-06-07 00:48