Synthesis of indole–quinoline–oxadiazoles

their anticancer potential and computational tubulin binding studies

Pooja R. Kamath, Dhanya Sunil, Abdul A. Ajees

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Abstract: Small hybrid molecules with two or more structural pharmacores having different biological functions and distinct activity have gained a significant role in cancer drug development to combat various types of malignancies. The present study describes an efficient, clean and strategic synthesis of 12 new substituted quinoline–indole–oxadiazole hybrids from substituted 2-(quinolin-8-yloxy)acetohydrazides and indole-3-carboxylic acids by employing T3P® as a green catalyst. Structures of the newly synthesized compounds were established by IR, 1H NMR, 13C NMR, DEPT C-NMR and MS spectroscopic evidence, as well as CHN analysis data. All indole–quinoline–oxadiazoles were tested for their in vitro cytotoxic potential in breast adenocarcinoma (MCF7) and normal kidney (vero) cell lines using MTT assay. 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline (3d) exhibited a low IC50 value and a high selectivity index to MCF7 cells and also displayed a mitotic block in flow cytometric cell cycle progression analysis. Microtubule disruption can induce G2/M phase cell cycle arrest leading to abnormal mitotic spindle formation. Ligand 3d demonstrated its capability of being a probable tubulin inhibitor when docked in the colchicine domain of tubulin. Graphical Abstract: New series of 8-((5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)methoxy)quinolines were synthesized using T3P® as a green catalyst and screened for their cytotoxic and antimitotic potential. The most active 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline 3d, displayed good binding interactions with the colchicine binding cavity of microtubule.[Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)5899-5914
Number of pages16
JournalResearch on Chemical Intermediates
Volume42
Issue number6
DOIs
Publication statusPublished - 01-06-2016

Fingerprint

Tubulin
Cells
Nuclear magnetic resonance
Colchicine
Tubulin Modulators
Quinolines
Antimitotic Agents
Catalysts
Assays
Ligands
Molecules
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

@article{68fd33a38a2f4d0e911d0f0b863a9c93,
title = "Synthesis of indole–quinoline–oxadiazoles: their anticancer potential and computational tubulin binding studies",
abstract = "Abstract: Small hybrid molecules with two or more structural pharmacores having different biological functions and distinct activity have gained a significant role in cancer drug development to combat various types of malignancies. The present study describes an efficient, clean and strategic synthesis of 12 new substituted quinoline–indole–oxadiazole hybrids from substituted 2-(quinolin-8-yloxy)acetohydrazides and indole-3-carboxylic acids by employing T3P{\^A}{\circledR} as a green catalyst. Structures of the newly synthesized compounds were established by IR, 1H NMR, 13C NMR, DEPT C-NMR and MS spectroscopic evidence, as well as CHN analysis data. All indole–quinoline–oxadiazoles were tested for their in vitro cytotoxic potential in breast adenocarcinoma (MCF7) and normal kidney (vero) cell lines using MTT assay. 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline (3d) exhibited a low IC50 value and a high selectivity index to MCF7 cells and also displayed a mitotic block in flow cytometric cell cycle progression analysis. Microtubule disruption can induce G2/M phase cell cycle arrest leading to abnormal mitotic spindle formation. Ligand 3d demonstrated its capability of being a probable tubulin inhibitor when docked in the colchicine domain of tubulin. Graphical Abstract: New series of 8-((5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)methoxy)quinolines were synthesized using T3P{\^A}{\circledR} as a green catalyst and screened for their cytotoxic and antimitotic potential. The most active 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline{\^A} 3d, displayed good binding interactions with the colchicine binding cavity of microtubule.[Figure not available: see fulltext.]",
author = "Kamath, {Pooja R.} and Dhanya Sunil and Ajees, {Abdul A.}",
year = "2016",
month = "6",
day = "1",
doi = "10.1007/s11164-015-2412-8",
language = "English",
volume = "42",
pages = "5899--5914",
journal = "Research on Chemical Intermediates",
issn = "0922-6168",
publisher = "Springer Netherlands",
number = "6",

}

TY - JOUR

T1 - Synthesis of indole–quinoline–oxadiazoles

T2 - their anticancer potential and computational tubulin binding studies

AU - Kamath, Pooja R.

AU - Sunil, Dhanya

AU - Ajees, Abdul A.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Abstract: Small hybrid molecules with two or more structural pharmacores having different biological functions and distinct activity have gained a significant role in cancer drug development to combat various types of malignancies. The present study describes an efficient, clean and strategic synthesis of 12 new substituted quinoline–indole–oxadiazole hybrids from substituted 2-(quinolin-8-yloxy)acetohydrazides and indole-3-carboxylic acids by employing T3P® as a green catalyst. Structures of the newly synthesized compounds were established by IR, 1H NMR, 13C NMR, DEPT C-NMR and MS spectroscopic evidence, as well as CHN analysis data. All indole–quinoline–oxadiazoles were tested for their in vitro cytotoxic potential in breast adenocarcinoma (MCF7) and normal kidney (vero) cell lines using MTT assay. 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline (3d) exhibited a low IC50 value and a high selectivity index to MCF7 cells and also displayed a mitotic block in flow cytometric cell cycle progression analysis. Microtubule disruption can induce G2/M phase cell cycle arrest leading to abnormal mitotic spindle formation. Ligand 3d demonstrated its capability of being a probable tubulin inhibitor when docked in the colchicine domain of tubulin. Graphical Abstract: New series of 8-((5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)methoxy)quinolines were synthesized using T3P® as a green catalyst and screened for their cytotoxic and antimitotic potential. The most active 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline 3d, displayed good binding interactions with the colchicine binding cavity of microtubule.[Figure not available: see fulltext.]

AB - Abstract: Small hybrid molecules with two or more structural pharmacores having different biological functions and distinct activity have gained a significant role in cancer drug development to combat various types of malignancies. The present study describes an efficient, clean and strategic synthesis of 12 new substituted quinoline–indole–oxadiazole hybrids from substituted 2-(quinolin-8-yloxy)acetohydrazides and indole-3-carboxylic acids by employing T3P® as a green catalyst. Structures of the newly synthesized compounds were established by IR, 1H NMR, 13C NMR, DEPT C-NMR and MS spectroscopic evidence, as well as CHN analysis data. All indole–quinoline–oxadiazoles were tested for their in vitro cytotoxic potential in breast adenocarcinoma (MCF7) and normal kidney (vero) cell lines using MTT assay. 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline (3d) exhibited a low IC50 value and a high selectivity index to MCF7 cells and also displayed a mitotic block in flow cytometric cell cycle progression analysis. Microtubule disruption can induce G2/M phase cell cycle arrest leading to abnormal mitotic spindle formation. Ligand 3d demonstrated its capability of being a probable tubulin inhibitor when docked in the colchicine domain of tubulin. Graphical Abstract: New series of 8-((5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)methoxy)quinolines were synthesized using T3P® as a green catalyst and screened for their cytotoxic and antimitotic potential. The most active 8-((5-(3-(1H-indol-3-yl)propyl)-1,3,4-oxadiazol-2-yl)methoxy)quinoline 3d, displayed good binding interactions with the colchicine binding cavity of microtubule.[Figure not available: see fulltext.]

UR - http://www.scopus.com/inward/record.url?scp=84954311432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954311432&partnerID=8YFLogxK

U2 - 10.1007/s11164-015-2412-8

DO - 10.1007/s11164-015-2412-8

M3 - Article

VL - 42

SP - 5899

EP - 5914

JO - Research on Chemical Intermediates

JF - Research on Chemical Intermediates

SN - 0922-6168

IS - 6

ER -