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Wietrzyk, J. et al.

Joanna Wietrzyk, Michał Chodyński, Hanna Fitak, Elzbieta Wojdat, Andrzej Kutner, Adam Opolski,

Antitumor properties of diastereomeric and geometric analogs of vitamin D3.

Analogs of 1,25-dihydroxyvitamin D3 with a reversed configuration at C-1 or C-24 and E or Z geometry of the double bond at C-22 in the side chain or at C-5 in the triene system were examined for their antiproliferative activity in vitro against a spectrum of various human cancer cell lines. The analogs coded PRI-2201 (calcipotriol), PRI-2202 and PRI-2205, such as calcitriol and tacalcitol (used as a referential agents), revealed antiproliferative activity against human HL-60, HL-60/MX2, MCF-7, T47D, SCC-25 and mouse WEHI-3 cancer cell lines. The toxicity studies in vivo showed that PRI-2202 and PRI-2205 are less toxic than referential agents. Even at total doses of 2.5-5.0 mg/kg distributed during 5 successive days, no changes in body weight were observed. Calcitriol and tacalcitol showed toxicity in the same protocol at 100 times lower doses. Calcipotriol was lethal to all mice after administration of a total dose of 5.0 mg/kg. The analog PRI-2205 appeared to be more active in mouse Levis lung cancer tumor growth inhibition than calcitriol, calcipotriol or PRI-2202. This analog did not reveal calcemic activity at doses which inhibit tumor growth in vivo nor at higher doses.[1]

References

Antitumor properties of diastereomeric and geometric analogs of vitamin D3. Wietrzyk, J., Chodyński, M., Fitak, H., Wojdat, E., Kutner, A., Opolski, A. Anticancer. Drugs (2007) [Pubmed]

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