2. Academic Validation
  3. The synthesis and biological evaluation of nucleobases/tetrazole hybrid compounds: A new class of phosphodiesterase type 3 (PDE3) inhibitors

The synthesis and biological evaluation of nucleobases/tetrazole hybrid compounds: A new class of phosphodiesterase type 3 (PDE3) inhibitors

  • Bioorg Med Chem. 2020 Jun 15;28(12):115540. doi: 10.1016/j.bmc.2020.115540.
Mohsen Shekouhy 1,  Somaye Karimian 2,  Ali Moaddeli 3,  Zeinab Faghih 4,  Yousef Delshad 5,  Ali Khalafi-Nezhad 6
Affiliations

Affiliations

  • 1 Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran. Electronic address: m.shekouhy@shirazu.ac.ir.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 3 Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran; Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.
  • 4 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 5 Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran.
  • 6 Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran. Electronic address: khalafi@shirazu.ac.ir.
PMID: 32503691 DOI: 10.1016/j.bmc.2020.115540
Abstract

Spired by the chemical structure of Cilostazol, a selective phosphodiesterase 3A (PDE3A) inhibitor, several novel hybrid compounds of nucleobases (uracil, 6-azauracil, 2-thiuracil, adenine, guanine, theophylline and theobromine) and tetrazole were designed and successfully synthesized and their inhibitory effects on PDE3A as well as their cytotoxicity on HeLa and MCF-7 cancerous cell lines were studied. Obtained results show the linear correlation between the inhibitory effect of synthesized compounds and their cytotoxicity. In some cases, the PDE3A inhibitory effects of synthesized compounds are higher than the Cilostazol. Besides, compared to a standard Anticancer drug methotrexate, some of the synthesized compounds showed the higher cytotoxicity against the HeLa and MCF-7 cancerous cell lines.

Keywords

Cilostazol; HeLa cell line; MCF-7 cell line; Nucleobase/tetrazole hybrid; Phosphodiesterase.

Figures