2. Academic Validation
  3. Synthesis of 2,3,6,7-tetramethoxyphenanthren-9-amine: An efficient precursor to access new 4-aza-2,3-dihydropyridophenanthrenes as apoptosis inducing agents

Synthesis of 2,3,6,7-tetramethoxyphenanthren-9-amine: An efficient precursor to access new 4-aza-2,3-dihydropyridophenanthrenes as apoptosis inducing agents

  • Eur J Med Chem. 2017 Feb 15:127:305-317. doi: 10.1016/j.ejmech.2017.01.001.
Niggula Praveen Kumar 1,  Pankaj Sharma 1,  T Srinivasa Reddy 2,  Shalini Nekkanti 1,  Nagula Shankaraiah 3,  Guntuku Lalita 4,  S Sujanakumari 4,  Suresh K Bhargava 2,  V G M Naidu 4,  Ahmed Kamal 5
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 2 Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Australia.
  • 3 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: shankar@niperhyd.ac.in.
  • 4 Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
  • 5 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India. Electronic address: ahmedkamal@iict.res.in.
PMID: 28068602 DOI: 10.1016/j.ejmech.2017.01.001
Abstract

A new route for the synthesis of novel 2,3,6,7-tetramethoxy phenanthrene amine precursor has been successfully accomplished. Subsequently, this amine precursor has been directly utilized for the synthesis of a new series of 4-aza-2,3-dihydropyridophenanthrene derivatives via a three component reaction with tetronic acid and substituted aldehydes. These compounds were evaluated for their cytotoxic potential against human lung (A549), prostate (PC-3 and DU145), breast (MDA-MB-231 and 4T1), gastric (HGC-27), colon (Caco-2) and cervical (HeLa) Cancer cell lines. Compound 10l showed significant Anticancer profile against DU145 cell line with an IC50 value of 2.6 ± 0.34 μM. Disruption of F-actin Cytoskeleton structure and cell migration inhibition in DU145 cells clearly indicate that the tumor progression and metastasis are affected by this compound (10l). Cell cycle analysis revealed that it arrests the cells in G2/M phase. Acridine orange/ethidium bromide (AO/EB) staining, Hoechst staining and annexin-V binding assays showed that cell proliferation is inhibited through induction of Apoptosis. Moreover, its treatment leads to collapse of the mitochondrial membrane potential (DΨm).

Keywords

2,3,6,7-Tetramethoxyphenanthren-9-amine; 4-Aza-2,3-dihydropyridophenanthrenes; Apoptosis; Cytotoxicity; Multi-component reaction; Perkin condensation.

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