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

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

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: esmaeili.rezvan@gmail.com.
  • 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: aforoumadi@yahoo.com.
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.

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