Ligand-based drug design: Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents

Dima A. Sabbah, Ameerah H. Ibrahim, Wamidh H. Talib, Khalid M. Alqaisi, Kamal Sweidan, Sanaa K. Bardaweel, Ghassan A. Sheikha, Haizhen A. Zhong, Eveen Al-Shalabi, Reema A. Khalaf, Mohammad S. Mubarak

Research output: Contribution to journalArticle

Abstract

Background: Phosphoinositide 3-kinase α (PI3Kα) has emerged as a promising target for anticancer drug design. Objectives: Target compounds were designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Ka complex interaction and antiproliferative activity. Methods: Synthesis of the proposed compounds, biological examination tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, along with Glide docking studies. Results: A series of 1,2-bis(4-methoxyphenyl)-2-oxoethyl benzoates was synthesized and characterized by means of FT-IR, 1H and 13C NMR, and by elemental analysis. Biological investigation demonstrated that the newly synthesized compounds exhibit antiproliferative activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines possibly via inhibition of PI3Ka and estrogen receptor alpha (ERa). Additionally, results revealed that these compounds exert selective inhibitory activity, induce apoptosis, and suppress VEGF production. Compound 3c exhibited promising antiproliferative activity in HCT-116 interrogating that hydrogen bond-acceptor mediates ligand/PI3Kα complex formation on m- position. Compounds 3e and 3i displayed high inhibitory activity in MCF-7 and T47D implying a wide cleft discloses the o-attachment. Furthermore, compound 3g exerted selective inhibitory activity against T47D. Glide docking studies against PI3Ka and ERa demonstrated that the series accommodate binding to PI3Kα and/or ERα. Conclusion: The series exhibited a potential antitumor activity in human carcinoma cell lines encoding PI3Kα and/or ERα.

Original languageEnglish (US)
Pages (from-to)417-429
Number of pages13
JournalMedicinal Chemistry
Volume15
Issue number4
DOIs
StatePublished - Jan 1 2019

Fingerprint

Benzoin
1-Phosphatidylinositol 4-Kinase
Drug Design
Antineoplastic Agents
Adenocarcinoma
Ligands
Estrogen Receptor alpha
Human Activities
Cell Line
Colon
Breast
Breast Neoplasms
Benzoates
Vascular Endothelial Growth Factor A
Hydrogen
Apoptosis
Carcinoma

Keywords

  • AKT
  • Angiogenesis
  • Caspase-3
  • Glide docking
  • HCT-116
  • MCF-7
  • P-anisoin
  • PI3Kα
  • T47D

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Sabbah, D. A., Ibrahim, A. H., Talib, W. H., Alqaisi, K. M., Sweidan, K., Bardaweel, S. K., ... Mubarak, M. S. (2019). Ligand-based drug design: Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents. Medicinal Chemistry, 15(4), 417-429. https://doi.org/10.2174/1573406414666180912111846

Ligand-based drug design : Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents. / Sabbah, Dima A.; Ibrahim, Ameerah H.; Talib, Wamidh H.; Alqaisi, Khalid M.; Sweidan, Kamal; Bardaweel, Sanaa K.; Sheikha, Ghassan A.; Zhong, Haizhen A.; Al-Shalabi, Eveen; Khalaf, Reema A.; Mubarak, Mohammad S.

In: Medicinal Chemistry, Vol. 15, No. 4, 01.01.2019, p. 417-429.

Research output: Contribution to journalArticle

Sabbah, DA, Ibrahim, AH, Talib, WH, Alqaisi, KM, Sweidan, K, Bardaweel, SK, Sheikha, GA, Zhong, HA, Al-Shalabi, E, Khalaf, RA & Mubarak, MS 2019, 'Ligand-based drug design: Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents', Medicinal Chemistry, vol. 15, no. 4, pp. 417-429. https://doi.org/10.2174/1573406414666180912111846
Sabbah, Dima A. ; Ibrahim, Ameerah H. ; Talib, Wamidh H. ; Alqaisi, Khalid M. ; Sweidan, Kamal ; Bardaweel, Sanaa K. ; Sheikha, Ghassan A. ; Zhong, Haizhen A. ; Al-Shalabi, Eveen ; Khalaf, Reema A. ; Mubarak, Mohammad S. / Ligand-based drug design : Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents. In: Medicinal Chemistry. 2019 ; Vol. 15, No. 4. pp. 417-429.
@article{9ba42be8171d4f4b9ad664f3928be66a,
title = "Ligand-based drug design: Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents",
abstract = "Background: Phosphoinositide 3-kinase α (PI3Kα) has emerged as a promising target for anticancer drug design. Objectives: Target compounds were designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Ka complex interaction and antiproliferative activity. Methods: Synthesis of the proposed compounds, biological examination tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, along with Glide docking studies. Results: A series of 1,2-bis(4-methoxyphenyl)-2-oxoethyl benzoates was synthesized and characterized by means of FT-IR, 1H and 13C NMR, and by elemental analysis. Biological investigation demonstrated that the newly synthesized compounds exhibit antiproliferative activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines possibly via inhibition of PI3Ka and estrogen receptor alpha (ERa). Additionally, results revealed that these compounds exert selective inhibitory activity, induce apoptosis, and suppress VEGF production. Compound 3c exhibited promising antiproliferative activity in HCT-116 interrogating that hydrogen bond-acceptor mediates ligand/PI3Kα complex formation on m- position. Compounds 3e and 3i displayed high inhibitory activity in MCF-7 and T47D implying a wide cleft discloses the o-attachment. Furthermore, compound 3g exerted selective inhibitory activity against T47D. Glide docking studies against PI3Ka and ERa demonstrated that the series accommodate binding to PI3Kα and/or ERα. Conclusion: The series exhibited a potential antitumor activity in human carcinoma cell lines encoding PI3Kα and/or ERα.",
keywords = "AKT, Angiogenesis, Caspase-3, Glide docking, HCT-116, MCF-7, P-anisoin, PI3Kα, T47D",
author = "Sabbah, {Dima A.} and Ibrahim, {Ameerah H.} and Talib, {Wamidh H.} and Alqaisi, {Khalid M.} and Kamal Sweidan and Bardaweel, {Sanaa K.} and Sheikha, {Ghassan A.} and Zhong, {Haizhen A.} and Eveen Al-Shalabi and Khalaf, {Reema A.} and Mubarak, {Mohammad S.}",
year = "2019",
month = "1",
day = "1",
doi = "10.2174/1573406414666180912111846",
language = "English (US)",
volume = "15",
pages = "417--429",
journal = "Medicinal Chemistry",
issn = "1573-4064",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Ligand-based drug design

T2 - Synthesis and biological evaluation of substituted benzoin derivatives as potential antitumor agents

AU - Sabbah, Dima A.

AU - Ibrahim, Ameerah H.

AU - Talib, Wamidh H.

AU - Alqaisi, Khalid M.

AU - Sweidan, Kamal

AU - Bardaweel, Sanaa K.

AU - Sheikha, Ghassan A.

AU - Zhong, Haizhen A.

AU - Al-Shalabi, Eveen

AU - Khalaf, Reema A.

AU - Mubarak, Mohammad S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Phosphoinositide 3-kinase α (PI3Kα) has emerged as a promising target for anticancer drug design. Objectives: Target compounds were designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Ka complex interaction and antiproliferative activity. Methods: Synthesis of the proposed compounds, biological examination tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, along with Glide docking studies. Results: A series of 1,2-bis(4-methoxyphenyl)-2-oxoethyl benzoates was synthesized and characterized by means of FT-IR, 1H and 13C NMR, and by elemental analysis. Biological investigation demonstrated that the newly synthesized compounds exhibit antiproliferative activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines possibly via inhibition of PI3Ka and estrogen receptor alpha (ERa). Additionally, results revealed that these compounds exert selective inhibitory activity, induce apoptosis, and suppress VEGF production. Compound 3c exhibited promising antiproliferative activity in HCT-116 interrogating that hydrogen bond-acceptor mediates ligand/PI3Kα complex formation on m- position. Compounds 3e and 3i displayed high inhibitory activity in MCF-7 and T47D implying a wide cleft discloses the o-attachment. Furthermore, compound 3g exerted selective inhibitory activity against T47D. Glide docking studies against PI3Ka and ERa demonstrated that the series accommodate binding to PI3Kα and/or ERα. Conclusion: The series exhibited a potential antitumor activity in human carcinoma cell lines encoding PI3Kα and/or ERα.

AB - Background: Phosphoinositide 3-kinase α (PI3Kα) has emerged as a promising target for anticancer drug design. Objectives: Target compounds were designed to investigate the effect of the p-OCH3 motifs on ligand/PI3Ka complex interaction and antiproliferative activity. Methods: Synthesis of the proposed compounds, biological examination tests against human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines, along with Glide docking studies. Results: A series of 1,2-bis(4-methoxyphenyl)-2-oxoethyl benzoates was synthesized and characterized by means of FT-IR, 1H and 13C NMR, and by elemental analysis. Biological investigation demonstrated that the newly synthesized compounds exhibit antiproliferative activity in human colon adenocarcinoma (HCT-116), breast adenocarcinoma (MCF-7), and breast carcinoma (T47D) cell lines possibly via inhibition of PI3Ka and estrogen receptor alpha (ERa). Additionally, results revealed that these compounds exert selective inhibitory activity, induce apoptosis, and suppress VEGF production. Compound 3c exhibited promising antiproliferative activity in HCT-116 interrogating that hydrogen bond-acceptor mediates ligand/PI3Kα complex formation on m- position. Compounds 3e and 3i displayed high inhibitory activity in MCF-7 and T47D implying a wide cleft discloses the o-attachment. Furthermore, compound 3g exerted selective inhibitory activity against T47D. Glide docking studies against PI3Ka and ERa demonstrated that the series accommodate binding to PI3Kα and/or ERα. Conclusion: The series exhibited a potential antitumor activity in human carcinoma cell lines encoding PI3Kα and/or ERα.

KW - AKT

KW - Angiogenesis

KW - Caspase-3

KW - Glide docking

KW - HCT-116

KW - MCF-7

KW - P-anisoin

KW - PI3Kα

KW - T47D

UR - http://www.scopus.com/inward/record.url?scp=85067114876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067114876&partnerID=8YFLogxK

U2 - 10.2174/1573406414666180912111846

DO - 10.2174/1573406414666180912111846

M3 - Article

C2 - 30207238

AN - SCOPUS:85067114876

VL - 15

SP - 417

EP - 429

JO - Medicinal Chemistry

JF - Medicinal Chemistry

SN - 1573-4064

IS - 4

ER -