An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor: Effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity

Marcia I. Dawson, Zebin Xia, Gang Liu, Joseph A. Fontana, Lulu Farhana, Bhamik B. Patel, Sankari Arumugarajah, Mohammad Bhuiyan, Xiao Kun Zhang, Young Hoon Han, William B. Stallcup, Jun Ichi Fukushi, Tomas Mustelin, Lutz Tautz, Ying Su, Danni L. Harris, Nahid Waleh, Peter D. Hobbs, Ling Jong, Wan Ru ChaoLeonard J. Schiff, Brahma P. Sani

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Apoptotic and antiproliferative activities of small heterodimer partner (SHP) nuclear receptor ligand (E)-4-[3′-(1-adamantyl)-4′- hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC), which was derived from 6-[3′-(1-adamantyl)-4′-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN), and several carboxyl isosteric or hydrogen bond-accepting analogues were examined. 3-Cl-AHPC continued to be the most effective apoptotic agent, whereas tetrazole, thiazolidine-2,4-dione, methyldinitrile, hydroxamic acid, boronic acid, 2-oxoaldehyde, and ethyl phosphonic acid hydrogen bond-acceptor analogues were inactive or less efficient inducers of KG-1 acute myeloid leukemia and MDA-MB-231 breast, H292 lung, and DU-145 prostate cancer cell apoptosis. Similarly, 3-Cl-AHPC was the most potent inhibitor of cell proliferation. 4-[3′-(1-Adamantyl)-4′-hydroxyphenyl]-3-chlorophenyltetrazole, (2E)-5-{2-[3′-(1-adamantyl)-2-chloro-4′-hydroxy-4-biphenyl]-ethenyl} -1H-tetrazole, 5-{4-[3′-(1-adamantyl)-4′-hydroxyphenyl]-3- chlorobenzylidene}diiazolidine-2,4-dione, and (3E)-4-[3′-(1-adamantyl)-2- chloro-4′-hydroxy-4-biphenyl]-2-oxobut-3-enal were very modest inhibitors of KG-1 proliferation. The other analogues were minimal inhibitors. Fragment-based QSAR analyses relating the polar termini with cancer cell growth inhibition revealed that length and van der Waals electrostatic surface potential were the most influential features on activity. 3-Cl-AHPC and the 3-chlorophenyltetrazole and 3-chlorobenzylidenethiazolidine-2,4-dione analogues were also able to inhibit SHP-2 protein-tyrosine phosphatase, which is elevated in some leukemias. 3-Cl-AHPC at 1.0 μM induced human microvascular endothelial cell apoptosis but did not inhibit cell migration or tube formation.

Original languageEnglish
Pages (from-to)2622-2639
Number of pages18
JournalJournal of Medicinal Chemistry
Volume50
Issue number11
DOIs
Publication statusPublished - May 31 2007

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Protein Tyrosine Phosphatases
Retinoids
Cytoplasmic and Nuclear Receptors
Apoptosis
Growth
Neoplasms
Hydrogen
Boronic Acids
Hydroxamic Acids
Quantitative Structure-Activity Relationship
Static Electricity
Acute Myeloid Leukemia
Cell Movement
4-(3-(1-adamantyl)-4-hydroxyphenyl)-3-chlorocinnamic acid
Prostatic Neoplasms
Leukemia
Breast
Endothelial Cells
Cell Proliferation
Ligands

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor : Effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity. / Dawson, Marcia I.; Xia, Zebin; Liu, Gang; Fontana, Joseph A.; Farhana, Lulu; Patel, Bhamik B.; Arumugarajah, Sankari; Bhuiyan, Mohammad; Zhang, Xiao Kun; Han, Young Hoon; Stallcup, William B.; Fukushi, Jun Ichi; Mustelin, Tomas; Tautz, Lutz; Su, Ying; Harris, Danni L.; Waleh, Nahid; Hobbs, Peter D.; Jong, Ling; Chao, Wan Ru; Schiff, Leonard J.; Sani, Brahma P.

In: Journal of Medicinal Chemistry, Vol. 50, No. 11, 31.05.2007, p. 2622-2639.

Research output: Contribution to journalArticle

Dawson, MI, Xia, Z, Liu, G, Fontana, JA, Farhana, L, Patel, BB, Arumugarajah, S, Bhuiyan, M, Zhang, XK, Han, YH, Stallcup, WB, Fukushi, JI, Mustelin, T, Tautz, L, Su, Y, Harris, DL, Waleh, N, Hobbs, PD, Jong, L, Chao, WR, Schiff, LJ & Sani, BP 2007, 'An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor: Effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity', Journal of Medicinal Chemistry, vol. 50, no. 11, pp. 2622-2639. https://doi.org/10.1021/jm0613323
Dawson, Marcia I. ; Xia, Zebin ; Liu, Gang ; Fontana, Joseph A. ; Farhana, Lulu ; Patel, Bhamik B. ; Arumugarajah, Sankari ; Bhuiyan, Mohammad ; Zhang, Xiao Kun ; Han, Young Hoon ; Stallcup, William B. ; Fukushi, Jun Ichi ; Mustelin, Tomas ; Tautz, Lutz ; Su, Ying ; Harris, Danni L. ; Waleh, Nahid ; Hobbs, Peter D. ; Jong, Ling ; Chao, Wan Ru ; Schiff, Leonard J. ; Sani, Brahma P. / An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor : Effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 11. pp. 2622-2639.
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abstract = "Apoptotic and antiproliferative activities of small heterodimer partner (SHP) nuclear receptor ligand (E)-4-[3′-(1-adamantyl)-4′- hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC), which was derived from 6-[3′-(1-adamantyl)-4′-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN), and several carboxyl isosteric or hydrogen bond-accepting analogues were examined. 3-Cl-AHPC continued to be the most effective apoptotic agent, whereas tetrazole, thiazolidine-2,4-dione, methyldinitrile, hydroxamic acid, boronic acid, 2-oxoaldehyde, and ethyl phosphonic acid hydrogen bond-acceptor analogues were inactive or less efficient inducers of KG-1 acute myeloid leukemia and MDA-MB-231 breast, H292 lung, and DU-145 prostate cancer cell apoptosis. Similarly, 3-Cl-AHPC was the most potent inhibitor of cell proliferation. 4-[3′-(1-Adamantyl)-4′-hydroxyphenyl]-3-chlorophenyltetrazole, (2E)-5-{2-[3′-(1-adamantyl)-2-chloro-4′-hydroxy-4-biphenyl]-ethenyl} -1H-tetrazole, 5-{4-[3′-(1-adamantyl)-4′-hydroxyphenyl]-3- chlorobenzylidene}diiazolidine-2,4-dione, and (3E)-4-[3′-(1-adamantyl)-2- chloro-4′-hydroxy-4-biphenyl]-2-oxobut-3-enal were very modest inhibitors of KG-1 proliferation. The other analogues were minimal inhibitors. Fragment-based QSAR analyses relating the polar termini with cancer cell growth inhibition revealed that length and van der Waals electrostatic surface potential were the most influential features on activity. 3-Cl-AHPC and the 3-chlorophenyltetrazole and 3-chlorobenzylidenethiazolidine-2,4-dione analogues were also able to inhibit SHP-2 protein-tyrosine phosphatase, which is elevated in some leukemias. 3-Cl-AHPC at 1.0 μM induced human microvascular endothelial cell apoptosis but did not inhibit cell migration or tube formation.",
author = "Dawson, {Marcia I.} and Zebin Xia and Gang Liu and Fontana, {Joseph A.} and Lulu Farhana and Patel, {Bhamik B.} and Sankari Arumugarajah and Mohammad Bhuiyan and Zhang, {Xiao Kun} and Han, {Young Hoon} and Stallcup, {William B.} and Fukushi, {Jun Ichi} and Tomas Mustelin and Lutz Tautz and Ying Su and Harris, {Danni L.} and Nahid Waleh and Hobbs, {Peter D.} and Ling Jong and Chao, {Wan Ru} and Schiff, {Leonard J.} and Sani, {Brahma P.}",
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T1 - An adamantyl-substituted retinoid-derived molecule that inhibits cancer cell growth and angiogenesis by inducing apoptosis and binds to small heterodimer partner nuclear receptor

T2 - Effects of modifying its carboxylate group on apoptosis, proliferation, and protein-tyrosine phosphatase activity

AU - Dawson, Marcia I.

AU - Xia, Zebin

AU - Liu, Gang

AU - Fontana, Joseph A.

AU - Farhana, Lulu

AU - Patel, Bhamik B.

AU - Arumugarajah, Sankari

AU - Bhuiyan, Mohammad

AU - Zhang, Xiao Kun

AU - Han, Young Hoon

AU - Stallcup, William B.

AU - Fukushi, Jun Ichi

AU - Mustelin, Tomas

AU - Tautz, Lutz

AU - Su, Ying

AU - Harris, Danni L.

AU - Waleh, Nahid

AU - Hobbs, Peter D.

AU - Jong, Ling

AU - Chao, Wan Ru

AU - Schiff, Leonard J.

AU - Sani, Brahma P.

PY - 2007/5/31

Y1 - 2007/5/31

N2 - Apoptotic and antiproliferative activities of small heterodimer partner (SHP) nuclear receptor ligand (E)-4-[3′-(1-adamantyl)-4′- hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC), which was derived from 6-[3′-(1-adamantyl)-4′-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN), and several carboxyl isosteric or hydrogen bond-accepting analogues were examined. 3-Cl-AHPC continued to be the most effective apoptotic agent, whereas tetrazole, thiazolidine-2,4-dione, methyldinitrile, hydroxamic acid, boronic acid, 2-oxoaldehyde, and ethyl phosphonic acid hydrogen bond-acceptor analogues were inactive or less efficient inducers of KG-1 acute myeloid leukemia and MDA-MB-231 breast, H292 lung, and DU-145 prostate cancer cell apoptosis. Similarly, 3-Cl-AHPC was the most potent inhibitor of cell proliferation. 4-[3′-(1-Adamantyl)-4′-hydroxyphenyl]-3-chlorophenyltetrazole, (2E)-5-{2-[3′-(1-adamantyl)-2-chloro-4′-hydroxy-4-biphenyl]-ethenyl} -1H-tetrazole, 5-{4-[3′-(1-adamantyl)-4′-hydroxyphenyl]-3- chlorobenzylidene}diiazolidine-2,4-dione, and (3E)-4-[3′-(1-adamantyl)-2- chloro-4′-hydroxy-4-biphenyl]-2-oxobut-3-enal were very modest inhibitors of KG-1 proliferation. The other analogues were minimal inhibitors. Fragment-based QSAR analyses relating the polar termini with cancer cell growth inhibition revealed that length and van der Waals electrostatic surface potential were the most influential features on activity. 3-Cl-AHPC and the 3-chlorophenyltetrazole and 3-chlorobenzylidenethiazolidine-2,4-dione analogues were also able to inhibit SHP-2 protein-tyrosine phosphatase, which is elevated in some leukemias. 3-Cl-AHPC at 1.0 μM induced human microvascular endothelial cell apoptosis but did not inhibit cell migration or tube formation.

AB - Apoptotic and antiproliferative activities of small heterodimer partner (SHP) nuclear receptor ligand (E)-4-[3′-(1-adamantyl)-4′- hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC), which was derived from 6-[3′-(1-adamantyl)-4′-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN), and several carboxyl isosteric or hydrogen bond-accepting analogues were examined. 3-Cl-AHPC continued to be the most effective apoptotic agent, whereas tetrazole, thiazolidine-2,4-dione, methyldinitrile, hydroxamic acid, boronic acid, 2-oxoaldehyde, and ethyl phosphonic acid hydrogen bond-acceptor analogues were inactive or less efficient inducers of KG-1 acute myeloid leukemia and MDA-MB-231 breast, H292 lung, and DU-145 prostate cancer cell apoptosis. Similarly, 3-Cl-AHPC was the most potent inhibitor of cell proliferation. 4-[3′-(1-Adamantyl)-4′-hydroxyphenyl]-3-chlorophenyltetrazole, (2E)-5-{2-[3′-(1-adamantyl)-2-chloro-4′-hydroxy-4-biphenyl]-ethenyl} -1H-tetrazole, 5-{4-[3′-(1-adamantyl)-4′-hydroxyphenyl]-3- chlorobenzylidene}diiazolidine-2,4-dione, and (3E)-4-[3′-(1-adamantyl)-2- chloro-4′-hydroxy-4-biphenyl]-2-oxobut-3-enal were very modest inhibitors of KG-1 proliferation. The other analogues were minimal inhibitors. Fragment-based QSAR analyses relating the polar termini with cancer cell growth inhibition revealed that length and van der Waals electrostatic surface potential were the most influential features on activity. 3-Cl-AHPC and the 3-chlorophenyltetrazole and 3-chlorobenzylidenethiazolidine-2,4-dione analogues were also able to inhibit SHP-2 protein-tyrosine phosphatase, which is elevated in some leukemias. 3-Cl-AHPC at 1.0 μM induced human microvascular endothelial cell apoptosis but did not inhibit cell migration or tube formation.

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