2. Academic Validation
  3. Design, synthesis, in silico pharmacokinetics prediction and biological evaluation of 1,4-dihydroindeno[1,2-c]pyrazole chalcone as EGFR /Akt pathway inhibitors

Design, synthesis, in silico pharmacokinetics prediction and biological evaluation of 1,4-dihydroindeno[1,2-c]pyrazole chalcone as EGFR /Akt pathway inhibitors

  • Eur J Med Chem. 2019 Feb 1:163:636-648. doi: 10.1016/j.ejmech.2018.12.011.
Irfan Khan 1,  Koteswara Rao Garikapati 2,  Aravind Setti 3,  Anver Basha Shaik 4,  Venkata Krishna Kanth Makani 5,  Mohd Adil Shareef 1,  Hemshikha Rajpurohit 4,  Namratha Vangara 5,  Manika Pal-Bhadra 6,  Ahmed Kamal 7,  C Ganesh Kumar 8
Affiliations

Affiliations

  • 1 Organic Synthesis and Process Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 2 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 3 Department of Genetics, Osmania University, Hyderabad 500007, India.
  • 4 Organic Synthesis and Process Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 5 Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 6 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Applied Biology Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: manika@iict.res.in.
  • 7 School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi 110062, India. Electronic address: ahmedkamal915@gmail.com.
  • 8 Organic Synthesis and Process Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: cgkumar.iict@gov.in.
PMID: 30562699 DOI: 10.1016/j.ejmech.2018.12.011
Abstract

In an attempt to develop potent and selective Anticancer agents, a series of 15 conjugates of 1,4-dihydroindeno[1,2-c]pyrazole chalcone (12a-o) were designed, synthesized and evaluated for their antiproliferative activity against MCF7, A549, MDA-MB-231, HCT116 and SKBR3 human Cancer cell lines. Among them, 12h, 12l and 12m showed IC50 values: 3.82, 5.33 and 4.21 μM, respectively, on A549 cell with respect to the positive control, Erlotinib (IC50 value: 10.26 μM). Detailed biological assays showed accumulation of mitotic cells in G2/M phase. In addition, Western blot analysis and immunofluorescence study revealed inhibition of EGFR and Akt pathways. In silico computational studies were also carried out to predict the binding modes and pharmacokinetic parameters of these conjugates.

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