Design, synthesis and evaluation of novel thienopyrimidine-based agents bearing diaryl urea functionality as potential inhibitors of angiogenesis

  • Eur J Med Chem. 2021 Jan 1:209:112942. doi: 10.1016/j.ejmech.2020.112942.
Aram Faraji  1 ,  Tayebeh Oghabi Bakhshaiesh  2 ,  Zaman Hasanvand  1 ,  Rasoul Motahari  1 ,  Elahe Nazeri  2 ,  Mohammad Amin Boshagh  2 ,  Loghman Firoozpour  3 ,  Hossein Mehrabi  4 ,  Ali Khalaj  1 ,  Rezvan Esmaeili  5 ,  Alireza Foroumadi  6
Affiliations
  • 1. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
  • 2. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
  • 3. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
  • 4. Department of Chemistry, Vali-e-Asr University of Rafsanjan, 77176, Rafsanjan, Iran.
  • 5. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran. Electronic address: [email protected].
  • 6. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. Electronic address: [email protected].
PMID: 33328104 DOI: 10.1016/j.ejmech.2020.112942
Abstract

Inhibition of angiogenesis is a promising strategy for the treatment of Cancer. Herein, we describe the design and synthesis of thieno[2,3-d]pyrimidine-1,3,4-thiadiazole-aryl urea derivatives 11a-m to evaluate their efficacy in the chick chorioallantoic membrane (CAM) assay. Among target agents, 11i had a considerable activity against prostate Cancer cell line, PC3 (IC50 = 3.6 μM). Moreover, induction of Apoptosis, good inhibitory activity against the growth of capillary blood vessels, and inhibition of VEGFR-2 phosphorylation were noticeable parameters which convinced us that 11i could be considered as a promising candidate for the discovery of novel drugs to treat tumors, particularly prostate Cancer.

Keywords
1,3,4-Thiadiazole; Angiogenesis; Apoptosis; CAM assay; PC3; Thieno[2,3-d]pyrimidine; VEGFR-2.