2. Academic Validation
  3. Synthesis of (Z)-1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(phenylamino)prop-2-en-1-one derivatives as potential anticancer and apoptosis inducing agents

Synthesis of (Z)-1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(phenylamino)prop-2-en-1-one derivatives as potential anticancer and apoptosis inducing agents

  • Eur J Med Chem. 2016 Jul 19:117:157-66. doi: 10.1016/j.ejmech.2016.03.051.
T Srinivasa Reddy 1,  V Ganga Reddy 2,  Hitesh Kulhari 1,  Ravi Shukla 3,  Ahmed Kamal 4,  Vipul Bansal 5
Affiliations

Affiliations

  • 1 Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Victoria 3000, Australia.
  • 2 Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
  • 3 Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Victoria 3000, Australia; Centre for Advanced Materials and Industrial Chemistry, School of Science, RMIT University, Melbourne, Victoria 3000, Australia.
  • 4 Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; IICT-RMIT Research Centre, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India. Electronic address: ahmedkamal@iict.res.in.
  • 5 Ian Potter NanoBioSensing Facility, NanoBiotechnology Research Laboratory, School of Science, RMIT University, Melbourne, Victoria 3000, Australia. Electronic address: vipul.bansal@rmit.edu.au.
PMID: 27092413 DOI: 10.1016/j.ejmech.2016.03.051
Abstract

A series of (Z)-1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(phenylamino)prop-2-en-1-one derivatives were synthesized and characterized by (1)H and (13)C NMR, ESI-MS and HRMS. All the synthesized compounds were evaluated for their Anticancer activity against HT-29, PC-3, A549 and U87MG human tumor cell lines. Most of the synthesized compounds displayed potent growth inhibition selectively of A549 Cancer cells and did not show significant toxicity to the non-cancerous HaCaT cells. Some of the representative compounds, particularly, 16, 22 and 28 exhibited potent growth inhibition with IC50 values in the range of 1.25-3.98 μM, which are comparable or even better than the standard chemotherapeutic drug 5-fluorouracil. Preliminary mechanistic studies revealed that these compounds could effectively inhibit the migration ability of A549 cells. Flow-cytometry analysis revealed that the compounds treatment led to G2/M cell cycle arrest. Moreover, the compounds induced Apoptosis in A549 cells through depolarization of mitochondrial membrane potential (DΨm) and increased Reactive Oxygen Species (ROS) production, suggesting their potential to act as promising lead compounds for the development of Cancer chemotherapeutics.

Keywords

Anti-cancer activity; Apoptosis; Cell cycle; Pyrazole.

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