Design, Synthesis and Biological Evaluation of Triptorelin Analogs Containing Tetrazole Moiety. Issue 4 (27th January 2020)

• Record Type: Journal Article
• Authors: Sohbati, Hamidreza; Alipour, Mohsen; Hosseinkhani, Saman; Balalaie, Saeed; Hamdan, Fatima
• Is Part Of: ChemistrySelect. Volume 5:Issue 4(2020)
• Page Start: 1443
• Page End: 1449
• Publication Date: 2020-01-27
• Subjects: Carboxylic acid bioisostere -- Peptidomimetic -- Prostate cancer -- Testosterone -- Tetrazole -- Triptorelin acetate.; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201903722
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: The design and synthesis of novel bioisosteric analogues of triptorelin acetate containing tetrazole moiety at C‐ or N‐terminus of the peptides is described. Tetrazole acetic acid was synthesized through the reaction of an alkyl cyanoacetate and sodium azide, after that, it was coupled to the N‐terminus of triptorelin instead of pyroglutamic acid. In another approach, tetrazole acetohydrazide was prepared and conjugated to the C‐terminus of triptorelin instead of the amide bond. The synthesized peptides containing tetrazole moiety at the C‐ or N‐terminus of the peptide sequence are peptidomimetics of triptorelin acetate. The docking results of the designed derivatives showed the same interaction of triptorelin with the receptor but with a higher score.The peptide that has tetrazole moiety in its C‐terminus, restricted the testosterone level during four weeks of in vivo study and led to keep testosterone at a moderate level during the first week compared to control. Abstract : An efficient approach for the synthesis of triptorelin acetate analogues is described. To achieve this goal tetrazole moiety as bioisostere of carboxylic acid was added in the C ‐ or N ‐terminus of the synthetic peptides. The synthesis of target peptides was done based on solid phase peptide synthesis approach. The biological activity of the synthesized peptides was investigated and compared to the triptorelin acetate.