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  3. Sulfamic acid promoted one-pot synthesis of phenanthrene fused-dihydrodibenzo-quinolinones: Anticancer activity, tubulin polymerization inhibition and apoptosis inducing studies

Sulfamic acid promoted one-pot synthesis of phenanthrene fused-dihydrodibenzo-quinolinones: Anticancer activity, tubulin polymerization inhibition and apoptosis inducing studies

  • Bioorg Med Chem. 2018 May 1;26(8):1996-2008. doi: 10.1016/j.bmc.2018.02.050.
Niggula Praveen Kumar 1,  Sowjanya Thatikonda 2,  Ramya Tokala 1,  S Sujana Kumari 3,  Uppu Jaya Lakshmi 3,  Chandraiah Godugu 4,  Nagula Shankaraiah 5,  Ahmed Kamal 6
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 2 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 3 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 4 Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: chandra.niperhyd@gov.in.
  • 5 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
  • 6 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 29525336 DOI: 10.1016/j.bmc.2018.02.050
Abstract

A facile one-pot method for the synthesis of new phenanthrene fused-dihydrodibenzo-quinolinone derivatives has been successfully accomplished by employing sulfamic acid as catalyst. These new compounds were evaluated for their in vitro cytotoxic potential against human lung (A549), prostate (PC-3 and DU145), breast (MCF-7) and colon (HT-29 and HCT-116) Cancer cell lines. Among all the tested compounds, one of the derivatives 8p showed good anti-proliferative activity against A549 lung Cancer cell line with an IC50 of 3.17 ± 0.52 µM. Flow cytometric analyses revealed that compound 8p arrested both Sub G1 and G2/M phases of cell cycle in a dose dependent manner. The compound 8p also displayed significant inhibition of tubulin polymerization and disruption of microtubule network (IC50 of 5.15 ± 0.15 µM). Molecular docking studies revealed that compound 8p efficiently interacted with critical amino acid Cys241 of the α/β-tubulin by a hydrogen bond (SH…O = 2.4 Å). Further, the effect of 8p on cell viability was also studied by AO/EB, DCFDA and DAPI staining. The apoptotic characteristic features revealed that 8p inhibited cell proliferation effectively through Apoptosis by inducing the ROS generation. Analysis of mitochondrial membrane potential through JC-1 staining and annexin V binding assay indicated the extent of Apoptosis in A549 Cancer cells.

Keywords

Apoptosis; One-pot reaction; Perkin condensation; Phenanthrene fused-dihydrodibenzo-quinolinones; Tubulin polymerization.

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