TY - JOUR
T1 - Synthesis and preliminary biological evaluation of β-carotene and retinoic acid oxidation products
AU - Kithsiri Wijeratne, E. M.
AU - Liu, Manping X.
AU - Kantipudi, Narendra B.
AU - Brochini, Claudia B.
AU - Leslie Gunatilaka, A. A.
AU - Canfield, Louise M.
N1 - Funding Information:
Financial support from American Institute for Cancer Research (Project 01A090-REV), and College of Agriculture and Life Sciences is gratefully acknowledged. CBB thanks FAPESP (Brazil) for a Fellowship.
PY - 2006/12/1
Y1 - 2006/12/1
N2 - Synthesis of the β-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-β-apo-carotene-13-one (1) was achieved in six steps starting from β-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and that 11 is significantly cytotoxic compared with the other retinoic acid analogs suggesting the requirement of the carboxylic acid moiety and the cis-geometry of the 13(14) double bond for cytotoxic activity.
AB - Synthesis of the β-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-β-apo-carotene-13-one (1) was achieved in six steps starting from β-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and that 11 is significantly cytotoxic compared with the other retinoic acid analogs suggesting the requirement of the carboxylic acid moiety and the cis-geometry of the 13(14) double bond for cytotoxic activity.
KW - DACE
KW - Oxidation products
KW - Retinoic acid
KW - Synthesis
KW - β-Carotene
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U2 - 10.1016/j.bmc.2006.07.057
DO - 10.1016/j.bmc.2006.07.057
M3 - Article
C2 - 16908162
AN - SCOPUS:33750085044
SN - 0968-0896
VL - 14
SP - 7875
EP - 7879
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 23
ER -