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

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.