4,6-diaryl pyrimidones as constrained chalcone analogues: Design, synthesis and evaluation as antiproliferative agents

Dinesh Kumar; Kunal Nepali; P. M.S. Bedi; Suresh Kumar; Fayaz Malik; Subheet Jain

doi:10.2174/1871520615666150318101436

4,6-diaryl pyrimidones as constrained chalcone analogues: Design, synthesis and evaluation as antiproliferative agents

Dinesh Kumar, Kunal Nepali, P. M.S. Bedi, Suresh Kumar, Fayaz Malik, Subheet Jain

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

13 Citations (Scopus)

Abstract

4,6-diarylpyrimidones as constrained chalcone analogues have been synthesised in the present study. The synthesised compounds were evaluated against a panel of human cancer cell lines. Striking selectivity was displayed by the compounds against MiaPaCa (Pancreatic) cell lines while PC-3 (prostate) and A-549 (lung) cell lines were almost resistant to the exposure of the test compounds. Compound SK – 25 exhibited remarkable cytotoxicity against MiaPaca-2 cell line with an IC₅₀ value of 1.95 μM and was found to induce apoptosis evidenced through phase contrast microscopy, DAPI staining and mitochondrial membrane potential loss. The cell phase distribution studies indicated that the apoptotic population increased from 1.79% in control sample to 30.33 % in sample treated with 20 μM compound SK-25.

Original language	English
Pages (from-to)	793-803
Number of pages	11
Journal	Anti-Cancer Agents in Medicinal Chemistry
Volume	15
Issue number	6
DOIs	https://doi.org/10.2174/1871520615666150318101436
Publication status	Published - Jul 1 2015
Externally published	Yes

Keywords

Apoptosis
Cell cycle
Chalcone
Contrained
Cytotoxic
Pyrimidones

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2174/1871520615666150318101436

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title = "4,6-diaryl pyrimidones as constrained chalcone analogues: Design, synthesis and evaluation as antiproliferative agents",

abstract = "4,6-diarylpyrimidones as constrained chalcone analogues have been synthesised in the present study. The synthesised compounds were evaluated against a panel of human cancer cell lines. Striking selectivity was displayed by the compounds against MiaPaCa (Pancreatic) cell lines while PC-3 (prostate) and A-549 (lung) cell lines were almost resistant to the exposure of the test compounds. Compound SK – 25 exhibited remarkable cytotoxicity against MiaPaca-2 cell line with an IC50 value of 1.95 μM and was found to induce apoptosis evidenced through phase contrast microscopy, DAPI staining and mitochondrial membrane potential loss. The cell phase distribution studies indicated that the apoptotic population increased from 1.79% in control sample to 30.33 % in sample treated with 20 μM compound SK-25.",

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author = "Dinesh Kumar and Kunal Nepali and Bedi, {P. M.S.} and Suresh Kumar and Fayaz Malik and Subheet Jain",

note = "Publisher Copyright: {\textcopyright} 2015 Bentham Science Publishers.",

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T1 - 4,6-diaryl pyrimidones as constrained chalcone analogues

T2 - Design, synthesis and evaluation as antiproliferative agents

AU - Kumar, Dinesh

AU - Nepali, Kunal

AU - Bedi, P. M.S.

AU - Kumar, Suresh

AU - Malik, Fayaz

AU - Jain, Subheet

PY - 2015/7/1

Y1 - 2015/7/1

N2 - 4,6-diarylpyrimidones as constrained chalcone analogues have been synthesised in the present study. The synthesised compounds were evaluated against a panel of human cancer cell lines. Striking selectivity was displayed by the compounds against MiaPaCa (Pancreatic) cell lines while PC-3 (prostate) and A-549 (lung) cell lines were almost resistant to the exposure of the test compounds. Compound SK – 25 exhibited remarkable cytotoxicity against MiaPaca-2 cell line with an IC50 value of 1.95 μM and was found to induce apoptosis evidenced through phase contrast microscopy, DAPI staining and mitochondrial membrane potential loss. The cell phase distribution studies indicated that the apoptotic population increased from 1.79% in control sample to 30.33 % in sample treated with 20 μM compound SK-25.

AB - 4,6-diarylpyrimidones as constrained chalcone analogues have been synthesised in the present study. The synthesised compounds were evaluated against a panel of human cancer cell lines. Striking selectivity was displayed by the compounds against MiaPaCa (Pancreatic) cell lines while PC-3 (prostate) and A-549 (lung) cell lines were almost resistant to the exposure of the test compounds. Compound SK – 25 exhibited remarkable cytotoxicity against MiaPaca-2 cell line with an IC50 value of 1.95 μM and was found to induce apoptosis evidenced through phase contrast microscopy, DAPI staining and mitochondrial membrane potential loss. The cell phase distribution studies indicated that the apoptotic population increased from 1.79% in control sample to 30.33 % in sample treated with 20 μM compound SK-25.

KW - Apoptosis

KW - Cell cycle

KW - Chalcone

KW - Contrained

KW - Cytotoxic

KW - Pyrimidones

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JO - Anti-Cancer Agents in Medicinal Chemistry

JF - Anti-Cancer Agents in Medicinal Chemistry

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ER -

4,6-diaryl pyrimidones as constrained chalcone analogues: Design, synthesis and evaluation as antiproliferative agents

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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