Design, synthesis and evaluation of anticancer activity of new pyrazoline derivatives by down-regulation of VEGF: Molecular docking and apoptosis inducing activity
Rasha A. Hassana, Soha Hussein Emama, Dukhyun Hwangb, Gun‐Do Kimb, Soha Osama Hassaninc, Mona G. Khalild, Amr M. Abdoue, Amr Sayed Motawi Sonousia f g✉
- aPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt
- bDepartment of Microbiology, College of Natural Sciences, Pukyong National University, Busan 48513, Korea
- cBiochemistry Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt
- dPharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt
- eDepartment of Microbiology and Immunology, National Research Centre, Dokki, Giza, 12622, Egypt
- fUniversity of Hertfordshire hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt. Electronic address: amr.motawi@pharma.cu.edu.eg
- gUniversity of Hertfordshire hosted by Global Academic Foundation, New Administrative Capital, Cairo, Egypt
- ✉Corresponding author
Papers open inside SciRah from the original publisher or repository; SciRah never hosts them.
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.
TL;DRTwo series of pyrazoline compounds designed and synthesized as antiproliferative agents by VEGFR pathway inhibition showed potent down-regulation of VEGF and p-VEGFR-2, which explains the VEGF down-regulation. (Semantic Scholar)