Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents

Poza, Javier; Rega, Miriam; Paz, Vanessa; Alonso, Beatriz; Rodrı́guez, Jaime; Salvador, Nélida; Fernández, Antonio; Jiménez, Carlos

doi:10.1016/j.bmc.2007.05.003

Cited by 48 publications

(28 citation statements)

References 22 publications

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“…Acetate intermediate [D 4 ]‐6 was then hydrolyzed with methanolic KOH to provide [D 4 ]‐4 β ‐hydroxycholesterol [D 4 ]‐1 after purification by flash column chromatography. 1 H NMR results compared favorably with unlabeled compound . Correlation spectroscopy (COSY) experiment was conducted to unambigously assign protons C3 and C4 and the 1 H NMR H‐H coupling constant of 3.27 Hz then confirmed the cis orientation at C3 and C4.…”

Section: Resultsmentioning

confidence: 98%

“…Poza et al . described using Petrows' re‐arrangement to incorporate a β ‐hydroxyl group at the C4 position of cholesterol . This route was more attractive from a labeling standpoint because [D 4 ]‐4 β ‐hydroxycholesterol [D 4 ]‐1 or [D 7 ]‐ 4 β ‐hydroxycholesterol [D 7 ]‐1 could be prepared from labeled cholesterol in fewer steps and in higher yield.…”

Section: Resultsmentioning

confidence: 99%

“…Both acetate intermediate [D 7 ]‐6 and [D 7 ]‐4 β ‐hydroxycholesterol [D 7 ]‐1 were purified by flash column chromatography. Each product was analyzed by 1 H NMR and compared with literature values for unlabeled compounds . COSY experiment on and [D 7 ]‐4 β ‐hydroxycholesterol [D 7 ]‐1 assigned protons C3 and C4 and 1 H NMR H‐H coupling constant of 3.02 Hz confirmed the cis orientation at C3 and C4 .…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of [D₄]‐ and [D₇]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay

Turley¹,

Burrell²,

Bonacorsi

et al. 2011

Labelled Comp Radiopharmac

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Cytochrome P450 3A (CYP3A) enzymes are involved in the metabolism of over half of today's prescription drugs. As a result, drugs metabolized by CYP3A have a risk of drug-drug interactions (DDIs). Recent studies have shown the potential to use 4b-hydroxycholesterol as an endogenous biomarker of CYP3A activity and predictor of potential DDIs. Bristol-Myers Squibb has developed a liquid chromatography-electron ionization-tandem mass spectrometry method that accurately measures 4b-hydroxycholesterol levels in clinical plasma samples following treatment with a CYP3A inducer or inhibitor. Stable isotope labeled (SIL) [D 4 ]-and [D 7 ]-4b-hydroxycholesterols were synthesized to assist in the development of this new quantification method. The SIL analogs were prepared from the appropriate [D 4 ]-or [D 7 ]-cholesterol starting material in two steps. The labeled cholesterols were oxidized with bromine and silver acetate in pyridine to give an acetate protected hydroxy group at C4. Hydrolysis of the acetate protecting group provided [D 4 ]-and [D 7 ]-4b-hydroxycholesterols in 15%-28% overall yield. 4a-Hydroxycholesterol was also required during method development and was prepared in four steps from cholesteryl benzoate in 1% overall yield.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Synthesis of [D₄]‐ and [D₇]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay

Turley¹,

Burrell²,

Bonacorsi

et al. 2011

Labelled Comp Radiopharmac

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“…In view of the literature reports [14,18,19] that 3,17-diketo steroids with higher degree of unsaturation in A-ring exhibit potent cytotoxicity, Oppenauer oxidation of 13-15 was carried out to afford a,b-unsaturated-3-keto steroids 16-18, respectively. A singlet for the 4-CH proton at about d 5.76 ppm and disappearance of 3a-H was observed in the 1 H NMR spectra of all the Oppenauer products.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and antileukemic activity of 16E-[4-(2-carboxy)ethoxybenzylidene]-androstene amides

Bansal

Acharya

2012

Steroids

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“…Compound 2 showed cytotoxicity with IC 50 of 1.25 μg/mL against P-388, A-549, HT-29 cells, and 2.5 μg/mL toward MEL-28 cells. Based on the results, different types of steroidal oxime derivatives were synthesized and their cytotoxicities were evaluated [3,4,5,6,7,8]. …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

et al. 2014

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Using analogues of some marine steroidal oximes as precursors, a series of aza-B-homocholestane derivatives possessing different substituted groups at the 3-position of the steroidal nucleus were synthesized. Their biological activity against cancer cell proliferation was determined with multiple cancer cell lines. Aza-B-homocholestane derivatives possessing 3-hydroxyl, 3-hydroximino and 3-thiosemicarbazone groups displayed remarkable cytotoxicity to cancer cells via apoptosis inducing mechanism. Compounds 5, 10, 12, 15 and 18 exhibited better potency to inhibit cancer cell proliferation. In addition, compound 15 was further evaluated with three dimensional (3D) multicellular spheroids assay to determine its potency against spheroid growth. The structure-activity relationship (SAR) generated in the studies is valuable for the design of novel chemotherapeutic agents.

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Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents

Cited by 48 publications

References 22 publications

Synthesis of [D₄]‐ and [D₇]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay

Synthesis of [D₄]‐ and [D₇]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay

Synthesis and antileukemic activity of 16E-[4-(2-carboxy)ethoxybenzylidene]-androstene amides

Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

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Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents

Cited by 48 publications

References 22 publications

Synthesis of [D4]‐ and [D7]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay

Synthesis of [D4]‐ and [D7]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay

Synthesis and antileukemic activity of 16E-[4-(2-carboxy)ethoxybenzylidene]-androstene amides

Synthesis and Evaluation of Some New Aza-B-homocholestane Derivatives as Anticancer Agents

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Product

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Synthesis of [D₄]‐ and [D₇]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay

Synthesis of [D₄]‐ and [D₇]‐4β‐hydroxycholesterols for use in a novel drug–drug interaction assay