2. Academic Validation
  3. Design, synthesis and evaluation of anticancer activity of new pyrazoline derivatives by down-regulation of VEGF: Molecular docking and apoptosis inducing activity

Design, synthesis and evaluation of anticancer activity of new pyrazoline derivatives by down-regulation of VEGF: Molecular docking and apoptosis inducing activity

  • Bioorg Chem. 2022 Jan;118:105487. doi: 10.1016/j.bioorg.2021.105487.
Rasha A Hassan 1,  Soha H Emam 1,  Dukhyun Hwang 2,  Gun-Do Kim 2,  Soha O Hassanin 3,  Mona G Khalil 4,  Amr M Abdou 5,  Amr Sonousi 6
Affiliations

Affiliations

  • 1 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  • 2 Department of Microbiology, College of Natural Sciences, Pukyong National University, Busan 48513, Korea.
  • 3 Biochemistry Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
  • 4 Pharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
  • 5 Department of Microbiology and Immunology, National Research Centre, Dokki, Giza, 12622, Egypt.
  • 6 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt; University of Hertfordshire hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt. Electronic address: [email protected].
PMID: 34798455 DOI: 10.1016/j.bioorg.2021.105487
Abstract

Two series of pyrazoline compounds were designed and synthesized as antiproliferative agents by VEGFR pathway inhibition. All synthesized compounds were screened by the National Cancer Institute (NCI), Bethesda, USA for Anticancer activity against 60 human Cancer cell lines. Compound 3f exhibited the highest Anticancer activity on the ovarian cell line (OVCAR-4) with IC50 = 0.29 μM and on the breast cell line (MDA-MB-468) with IC50 = 0.35 μM. It also exhibited the highest selectivity index (SI = 74). Compound 3f caused cell cycle arrest in OVCAR-4 cell line at the S phase which consequently inhibited cell proliferation and induced Apoptosis. Moreover, 3f showed potent down-regulation of VEGF and p-VEGFR-2. Docking studies showed that compound 3f interacts in a similar pattern to axitinib on the VEGFR-2 receptor. The same compound was also able to fit into the gorge of STAT3 binding site, the transcription factor for VEGF, which explains the VEGF down-regulation.

Keywords

Anticancer; Apoptosis; Cell cycle analysis; Pyrazoline; STAT3; VEGF.

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