- Selective cytotoxicity of oxysterols through structural modulation on rings A and B. Synthesis, in vitro evaluation, and SAR
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Chemically diverse oxysterols were prepared and evaluated for cytotoxicity, aiming to push forward potency and selectivity. They were tested against seven cancer (HT-29, HepG2, A549, PC3, LAMA-84, MCF-7, and SH-SY5Y) and two noncancerous cell lines (ARPE-
- Carvalho, Jo?o F. S.,Silva, M. Manuel Cruz,Moreira, Jo?o N.,Sim?es, Sérgio,Sá E Melo, M. Luisa
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p. 6375 - 6393
(2011/11/06)
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- Synthesis of oxygenated cholesterols as structural mimics of phorbol ester-type tumor promoters
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We designed several oxygenated steroids in which functional groups including a hydrophobic group are arranged analogously to those of phorbol ester (12-O-tetradecanoylphorbol-13-acetate, TPA), with the aim of finding compounds with TPA-like activity, but having a different skeleton and a rigid conformation. The designed steroids, 1β,5α-dihydroxy-3β- hydroxymethylcholestan-6-one (4), 3β,5α-dihydroxycholestan-6-one (5), 3β- hydroxymethylcholestan-5α-ol-6-one (6) and 1β,3β,5α-trihydroxycholestan- 6-one (7), were synthesized. A related oxygenated steroid isolated from soft coral, cholestane-1β,3β,5α,6β-tetrol (8), was also synthesized. Among these analogs, compound 7 showed weak TPA-like activities in three biological tests: inhibition of [3H]TPA binding to protein kinase C and to cytosolic- nuclear tumor promoter-binding protein (CN-TPBP), and induction of differentiation of human promyelocytic leukemia cells (HL-60) to monocyte- like cells. On the other hand, compound 5 was found to be a specific ligand for CN-TPBP, but lacked the other TPA-like activities.
- Endo,Fukasawa,Hashimoto,Shudo
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p. 462 - 469
(2007/10/02)
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- Neighbouring Group Effects. Part 2. Effect of Epoxide on the Hydrolysis of Adjacent Acetate Groups
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The presence of an epoxide at the 4,5-position of a steroid accelerates the hydrolysis of an acetate group at the 3β or 6β-positions.This effect is also observed for a 1α-acetoxy-2β,3β-epoxide.A suitable fixed dipole-dipole orientation between the ester group and the adjacent polar group may be an important factor in the rate acceleration, since this neighbouring effect does not occur when a non-rigid side chain is present.Fliorine or bromine substitution at the 5α-position also enhances the rate of hydrolysis of 6β-acetoxy-group.
- Ishiguro, Masaji,Saito, Hiromitsu,Ikekawa, Nobuo
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p. 2507 - 2510
(2007/10/02)
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- Lewis acid-catalyzed rearrangement of steroidal oxetanes: revision of the course of solvolysis of 3β-tosyloxy-5β-cholestan-5-ol-6-one.
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The BF3-catalysed rearrangement of 6β-acetoxy-3α,5-epoxy-5α-cholestane gave the 3α,5β-diol, the 3α,10α-epoxide, and the 2α,5α-epoxide, and the product of solvolysis of 3β-tosyloxy-5β-cholestan-5-ol-6-one was identified as 3α,5-epoxy-A-homo-B-nor-5α-cholestan-4a-one.
- Foster, Richard W.G.,Maples, Brian A.
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p. 2071 - 2074
(2007/10/10)
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