In-vitro cytotoxicity of synthesized phthalide-fused indoles and indolines against HL-60 and HepG2 cells

Wong Sheryn, Masayuki Ninomiya, Mamoru Koketsu, Siti Aishah Hasbullah

Research output: Contribution to journalArticle

Abstract

Phthalide derivatives bearing indole or indoline moieties were successfully synthesized via eco-friendly method and were evaluated for their antiproliferative activity on HL-60 and HepG2 cell lines in vitro. At a final concentration of 100 μM, most of the compounds showed moderate potency on both the cell lines tested. Compound 3b bearing 5-chloro substituted indoline had the best potency against HL-60 and HepG2 cell lines with IC 50 values of 45.4 and 57.7 μM, respectively. It was also found that replacement of a conjugated indoline to indole moiety gave better antiproliferative activity on HL-60 cells by almost two-fold. Morphological observation demonstrated numerous fragmented nuclei which are indicative of apoptosis. Molecular docking studies predicted non-covalent interactions and H-bonding of selected compounds with the P2 binding hot spot of the anti-apoptotic protein, Bcl-2, formed by Asp108, Phe109, Met112, Leu134, Arg143, Ala146 and Val153. Overall, our work highlights the potential of synthesized phthalide-fused indoles or indolines as antitumor agents.

Original languageEnglish
JournalArabian Journal of Chemistry
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Indoles
Bearings (structural)
Cytotoxicity
Cells
Cell death
Apoptosis Regulatory Proteins
Antineoplastic Agents
Derivatives
Proteins
Apoptosis
indoline
phthalide
indole

Keywords

  • Antiproliferative activity
  • Indole
  • Indoline
  • Molecular docking
  • Phthalide

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

In-vitro cytotoxicity of synthesized phthalide-fused indoles and indolines against HL-60 and HepG2 cells. / Sheryn, Wong; Ninomiya, Masayuki; Koketsu, Mamoru; Hasbullah, Siti Aishah.

In: Arabian Journal of Chemistry, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Ninomiya, Masayuki

AU - Koketsu, Mamoru

AU - Hasbullah, Siti Aishah

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AB - Phthalide derivatives bearing indole or indoline moieties were successfully synthesized via eco-friendly method and were evaluated for their antiproliferative activity on HL-60 and HepG2 cell lines in vitro. At a final concentration of 100 μM, most of the compounds showed moderate potency on both the cell lines tested. Compound 3b bearing 5-chloro substituted indoline had the best potency against HL-60 and HepG2 cell lines with IC 50 values of 45.4 and 57.7 μM, respectively. It was also found that replacement of a conjugated indoline to indole moiety gave better antiproliferative activity on HL-60 cells by almost two-fold. Morphological observation demonstrated numerous fragmented nuclei which are indicative of apoptosis. Molecular docking studies predicted non-covalent interactions and H-bonding of selected compounds with the P2 binding hot spot of the anti-apoptotic protein, Bcl-2, formed by Asp108, Phe109, Met112, Leu134, Arg143, Ala146 and Val153. Overall, our work highlights the potential of synthesized phthalide-fused indoles or indolines as antitumor agents.

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