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Research on Chemical Intermediates

, Volume 44, Issue 5, pp 3031–3059 | Cite as

Ultrasound-mediated synthesis, biological evaluation, docking and in vivo acute oral toxicity study of novel indolin-2-one coupled pyrimidine derivatives

  • Anna Pratima G. Nikalje
  • Shailee V. Tiwari
  • Jaiprakash N. Sangshetti
  • Manoj D. Damale
Article

Abstract

The work reports ultrasound-mediated greener synthesis of 11 novel 3-(4-(4-chlorophenyl)-6-(substituted phenyl/heteryl)pyrimidin-2-ylimino)indolin-2-one (7a7k) derivatives. The synthesized derivatives were evaluated for their in vitro anticancer activity against a panel of selected human cancer cell lines of breast (MCF-7), cervix (HeLa), prostate (PC-3) and lung (A-549). Among the tested compounds, 7b exhibited most promising in vitro anticancer activity against HeLa, PC-3 and A-549 with GI50 value 15.38, 19.67 and 4.37 µM, respectively. The compounds (7a7k) were also screened for induction of apoptosis and morphological changes in cancer cells at their GI50 concentration. The treatment of HeLa, PC-3 and A549 cancer cells with 7b and treatment of MCF-7 cancer cells with 7h showed apoptosis and morphological changes such as cell shrinkage, cell wall deformation and reduced number of viable cells. The compound 7b has shown almost 5.00 times more selectivity for PC-3 cancer cell lines in comparison to the RWPE-1 normal prostate epithelial cells. Molecular docking study has been carried out, which replicates results of biological activity in cases of initial hits 7b, 7c and 7d, suggesting that these compounds have a potential to become lead molecules in the drug discovery process. In silico ADMET study was performed for predicting pharmacokinetic properties and toxicity profile of the synthesized compounds and expressed good oral drug-like behaviour. An in vivo acute oral toxicity study was performed using Swiss albino mice for the most active compounds 7b and 7c, and results indicate that the compounds are non-toxic in nature.

Keywords

Ultrasound mediated Indolin-2-one In vitro anticancer activity Molecular docking In vivo acute oral toxicity 

Notes

Acknowledgements

The authors are thankful to Mrs. Fatima Zakaria, Chairman Maulana Azad Educational Trust and Dr. Zahid Zaheer, Principal, Y.B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Aurangabad 431 001 (M.S.), India for providing the laboratory facility.

Compliance with ethical standards

Conflict of interest

The authors confirm that this article content has no conflict of interest.

Supplementary material

11164_2018_3292_MOESM1_ESM.doc (1 mb)
Supplementary material 1 (DOC 1072 kb)

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Anna Pratima G. Nikalje
    • 1
  • Shailee V. Tiwari
    • 1
  • Jaiprakash N. Sangshetti
    • 1
  • Manoj D. Damale
    • 1
  1. 1.Y.B. Chavan College of PharmacyAurangabadIndia

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