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Synthesis and biological evaluation of novel C1 or C3 amino derivatives of A-ring 1,2,3-trisubstituted 19-nor-vitamin D.

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Bioorganic & medicinal chemistry 📖 저널 OA 5.3% 2024: 0/3 OA 2025: 0/27 OA 2026: 4/43 OA 2024~2026 2026 Vol.134() p. 118523
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González-García T, Verlinden L, Doms S, Verstuyf A, Fernández S, Ferrero M

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Two new analogs of 1α,25-dihydroxy-19-nor-vitamin D with an additional hydroxyl group at position 2 and an amino group at C1 or C3 using quinic acid as starting substrate for the A-ring precursor are

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APA González-García T, Verlinden L, et al. (2026). Synthesis and biological evaluation of novel C1 or C3 amino derivatives of A-ring 1,2,3-trisubstituted 19-nor-vitamin D.. Bioorganic & medicinal chemistry, 134, 118523. https://doi.org/10.1016/j.bmc.2025.118523
MLA González-García T, et al.. "Synthesis and biological evaluation of novel C1 or C3 amino derivatives of A-ring 1,2,3-trisubstituted 19-nor-vitamin D.." Bioorganic & medicinal chemistry, vol. 134, 2026, pp. 118523.
PMID 41411886 ↗

Abstract

Two new analogs of 1α,25-dihydroxy-19-nor-vitamin D with an additional hydroxyl group at position 2 and an amino group at C1 or C3 using quinic acid as starting substrate for the A-ring precursor are described. Key step was the deprotection of the N-benzyl group mediated by an efficient biocatalytic system of Laccase from Trametes versicolor together with TEMPO. The synthesized analogs did not exhibit any significant affinity for binding to either the VDR or hDBP when compared to the natural hormone and 1α,25-dihydroxy-19-nor-vitamin D. In terms of their antiproliferative activity in MCF-7 and HL-60 cells, the reported influence of the hydroxyl group at C1 on biological activity of vitamin D analogs is observed. The 1α,2α-dihydroxy-3α-amino derivative was most active than 1β-Amino-2β,25-dihydroxy-19-nor-vitamin D, exhibiting an antiproliferative activity in breast cancer MCF-7 cells at a concentration of 10 M comparable with 1α,25-(OH)-D and 1α,25-(OH)-19-nor-D, but this compound was five times less potent than the natural hormone at the EC concentration.

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