1-(hydroxyalkyl)-25-hydroxyvitamin D3 analogs of calcitriol. 2. Preliminary biological evaluation

Gary H. Posner; Kathryn Z. Guyton; Thomas W. Kensler; Julia Barsony; Mara E. Lieberman; G. Satyanarayana Reddy; Jeffrey W. Clark; Khursheed F. Wankadiya; Kou Ti Tserng

doi:10.1016/S0960-894X(00)80115-8

1-(hydroxyalkyl)-25-hydroxyvitamin D₃ analogs of calcitriol. 2. Preliminary biological evaluation

Gary H. Posner, Kathryn Z. Guyton, Thomas W. Kensler, Julia Barsony, Mara E. Lieberman, G. Satyanarayana Reddy, Jeffrey W. Clark, Khursheed F. Wankadiya, Kou Ti Tserng

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

1α-Hydroxymethyl-25-hydroxyvitamin D₃ homology (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes. 1α-Hydroxymethyl-25-hydroxyvitamin D₃ homolog (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes.

Original language	English (US)
Pages (from-to)	1835-1840
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	3
Issue number	9
DOIs	https://doi.org/10.1016/S0960-894X(00)80115-8
State	Published - Sep 1993

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0960-894X(00)80115-8

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title = "1-(hydroxyalkyl)-25-hydroxyvitamin D3 analogs of calcitriol. 2. Preliminary biological evaluation",

abstract = "1α-Hydroxymethyl-25-hydroxyvitamin D3 homology (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes. 1α-Hydroxymethyl-25-hydroxyvitamin D3 homolog (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes.",

author = "Posner, {Gary H.} and Guyton, {Kathryn Z.} and Kensler, {Thomas W.} and Julia Barsony and Lieberman, {Mara E.} and Reddy, {G. Satyanarayana} and Clark, {Jeffrey W.} and Wankadiya, {Khursheed F.} and Tserng, {Kou Ti}",

year = "1993",

month = sep,

doi = "10.1016/S0960-894X(00)80115-8",

language = "English (US)",

volume = "3",

pages = "1835--1840",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - 1-(hydroxyalkyl)-25-hydroxyvitamin D3 analogs of calcitriol. 2. Preliminary biological evaluation

AU - Posner, Gary H.

AU - Guyton, Kathryn Z.

AU - Kensler, Thomas W.

AU - Barsony, Julia

AU - Lieberman, Mara E.

AU - Reddy, G. Satyanarayana

AU - Clark, Jeffrey W.

AU - Wankadiya, Khursheed F.

AU - Tserng, Kou Ti

PY - 1993/9

Y1 - 1993/9

N2 - 1α-Hydroxymethyl-25-hydroxyvitamin D3 homology (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes. 1α-Hydroxymethyl-25-hydroxyvitamin D3 homolog (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes.

AB - 1α-Hydroxymethyl-25-hydroxyvitamin D3 homology (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes. 1α-Hydroxymethyl-25-hydroxyvitamin D3 homolog (-)-2 shows: (1) increased expression of early and late murine epidermal differentiation markers; (2) weak induction of 24-hydroxylase activity in cultured porcine kidney epithelial cells; (3) strong resistance to metabolism in human leukemic cells; and (4) no significant antiproliferative (antimitogenic) activity in human leukemic cells. Surprisingly, 1-(hydroxyethyl) diastereomer (+)-5 is easily metabolized in human leukemic cells, and this 1β-homolog (+)-5 is several-fold less active than calcitriol but unexpectedly much more potent than 1α-homolog (-)-4 in inhibiting proliferation of murine keratinocytes.

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ER -

1-(hydroxyalkyl)-25-hydroxyvitamin D₃ analogs of calcitriol. 2. Preliminary biological evaluation

Abstract

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