Multicomponent synthesis of novel spiro-indoline-3,4'-pyran derivatives: in silico and in vitro study

  • Sci Rep. 2026 Jun 27. doi: 10.1038/s41598-026-59414-w.
Zahra Jamshidi  1  2 ,  Seyed Mohammad Taghdisi  3  4 ,  Khalil Abnous  1  5 ,  Razieh Ghodsi  1  6 ,  Farzin Hadizadeh  7  8
Affiliations
  • 1. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 2. Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 3. Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 4. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 5. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 6. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 7. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. [email protected].
  • 8. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. [email protected].
PMID: 42373729 DOI: 10.1038/s41598-026-59414-w
Abstract

In this work, a series of 15 novel spiro-indoline-3,4'-pyrans (4) were synthesized by a simple multi-component reaction. Several spectroscopic methods were used to fully characterize the produced compounds 4a-o. Compounds 4e, and 4f demonstrated Anticancer effects on the MCF-7 breast Cancer cell line (IC50 = 9.19 ± 1.29 µM and 2.93 ± 1.79 µM, respectively) by MTT assay. In addition, MCF-7 cells treated with compounds 4e and 4f showed a lower number of colonies in the colony formation assay than the control group. Compounds 4e and 4f demonstrated significant apoptotic effects on MCF-7 cells with a percentage of Apoptosis (early and late) of 53.1% and 46%, respectively. Finally, the best docked pose of compounds 4e and 4f against CDK2 was selected for further molecular dynamics (MD) simulation studies. Our data suggest that spiro-indoline-3,4'-pyran is a suitable core for optimization to identify novel Anticancer agents.

Keywords
CDK2 inhibitor; Isatin; Malononitrile; Multicomponent reactions; Small molecule; Spirooxindole.
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