Synthesis of gossypol atropisomers and derivatives and evaluation of their anti-proliferative and anti-oxidant activity.

Kalliopi Dodou; Rosaleen J. Anderson; W. John Lough; David A.P. Small; Michael D. Shelley; Paul W. Groundwater

doi:10.1016/j.bmc.2005.04.026

Synthesis of gossypol atropisomers and derivatives and evaluation of their anti-proliferative and anti-oxidant activity.

Kalliopi Dodou, Rosaleen J. Anderson, W. John Lough, David A.P. Small, Michael D. Shelley, Paul W. Groundwater

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

Abstract

Gossypol 1, gossypolone 2, and a series of bis 3 and half Schiff’s bases 4 of gossypol were synthesised and tested for anti-proliferative and anti-oxidant activity. (−)-Gossypol (−)-1 was the most potent inhibitor of the proliferation of the HPV-16 keratinocyte cell line (using an MTT viability assay) with a GI50 of 4.8 μM. The bis Schiff’s base of (−)-gossypol with l-tyrosine ethyl ester (−)-3b was the most potent inhibitor of iron/ascorbate dependent lipid peroxidation (using the thiobarbituric acid test), with an IC50 of 11.7 μM, with (−)-gossypol being the next most potent of the series, with an IC50 of 13.1 μM. The results from these initial assays suggest that gossypol, as either a racemic mixture rac-1, or the individual atropisomers (−)-1 or (+)-1, has potential for the treatment of psoriasis.

Original language	English
Pages (from-to)	4228-4237
Journal	Bioorganic and Medicinal Chemistry
DOIs	https://doi.org/10.1016/j.bmc.2005.04.026
Publication status	Published - 1 Jul 2005
Externally published	Yes

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@article{f613a3eeeea646c8bb050ae0f5c5fc9e,

title = "Synthesis of gossypol atropisomers and derivatives and evaluation of their anti-proliferative and anti-oxidant activity.",

abstract = "Gossypol 1, gossypolone 2, and a series of bis 3 and half Schiff{\textquoteright}s bases 4 of gossypol were synthesised and tested for anti-proliferative and anti-oxidant activity. (−)-Gossypol (−)-1 was the most potent inhibitor of the proliferation of the HPV-16 keratinocyte cell line (using an MTT viability assay) with a GI50 of 4.8 μM. The bis Schiff{\textquoteright}s base of (−)-gossypol with l-tyrosine ethyl ester (−)-3b was the most potent inhibitor of iron/ascorbate dependent lipid peroxidation (using the thiobarbituric acid test), with an IC50 of 11.7 μM, with (−)-gossypol being the next most potent of the series, with an IC50 of 13.1 μM. The results from these initial assays suggest that gossypol, as either a racemic mixture rac-1, or the individual atropisomers (−)-1 or (+)-1, has potential for the treatment of psoriasis.",

author = "Kalliopi Dodou and Anderson, {Rosaleen J.} and Lough, {W. John} and Small, {David A.P.} and Shelley, {Michael D.} and Groundwater, {Paul W.}",

year = "2005",

month = jul,

day = "1",

doi = "10.1016/j.bmc.2005.04.026",

language = "English",

pages = "4228--4237",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

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T1 - Synthesis of gossypol atropisomers and derivatives and evaluation of their anti-proliferative and anti-oxidant activity.

AU - Dodou, Kalliopi

AU - Anderson, Rosaleen J.

AU - Lough, W. John

AU - Small, David A.P.

AU - Shelley, Michael D.

AU - Groundwater, Paul W.

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Gossypol 1, gossypolone 2, and a series of bis 3 and half Schiff’s bases 4 of gossypol were synthesised and tested for anti-proliferative and anti-oxidant activity. (−)-Gossypol (−)-1 was the most potent inhibitor of the proliferation of the HPV-16 keratinocyte cell line (using an MTT viability assay) with a GI50 of 4.8 μM. The bis Schiff’s base of (−)-gossypol with l-tyrosine ethyl ester (−)-3b was the most potent inhibitor of iron/ascorbate dependent lipid peroxidation (using the thiobarbituric acid test), with an IC50 of 11.7 μM, with (−)-gossypol being the next most potent of the series, with an IC50 of 13.1 μM. The results from these initial assays suggest that gossypol, as either a racemic mixture rac-1, or the individual atropisomers (−)-1 or (+)-1, has potential for the treatment of psoriasis.

AB - Gossypol 1, gossypolone 2, and a series of bis 3 and half Schiff’s bases 4 of gossypol were synthesised and tested for anti-proliferative and anti-oxidant activity. (−)-Gossypol (−)-1 was the most potent inhibitor of the proliferation of the HPV-16 keratinocyte cell line (using an MTT viability assay) with a GI50 of 4.8 μM. The bis Schiff’s base of (−)-gossypol with l-tyrosine ethyl ester (−)-3b was the most potent inhibitor of iron/ascorbate dependent lipid peroxidation (using the thiobarbituric acid test), with an IC50 of 11.7 μM, with (−)-gossypol being the next most potent of the series, with an IC50 of 13.1 μM. The results from these initial assays suggest that gossypol, as either a racemic mixture rac-1, or the individual atropisomers (−)-1 or (+)-1, has potential for the treatment of psoriasis.

UR - http://europepmc.org/abstract/med/15878283

U2 - 10.1016/j.bmc.2005.04.026

DO - 10.1016/j.bmc.2005.04.026

M3 - Article

C2 - 15878283

SN - 0968-0896

SP - 4228

EP - 4237

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

ER -

Synthesis of gossypol atropisomers and derivatives and evaluation of their anti-proliferative and anti-oxidant activity.

Abstract

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