Synthesis, radioiodination and biological evaluation of novel dipeptide attached to triazole-pyridine moiety

Abstract

A new dipeptide derivative, ethyl 2-(3-(4-hydroxyphenyl)-2-(2-(4-phenyl-5-((pyridin-4-ylamino)methyl)-4H-1,2,4-triazol-3-ylthio)acetamido)propanamido)-3-(1H-indol-3-yl)propanoate (EHPTIP) was successfully synthesized and radiolabeled with 125I by the direct electrophilic substitution method. The non radiolabeled compound (EHPTIP) was tested as an antimicrobial agent and the radiolabeled derivative was tested as a new imaging agent. The study results showed a good antimicrobial activity of EHPTIP and a good in vitro and in vivo stability of 125I-EHPTIP. The biodistribution of the radiolabeled compound showed a high brain uptake of 7.60 ± 0.01 injected activity/g tissue organ at 30 min post-injection and retention in brain remained high up to 1 h, whereas the clearance from the normal mice appeared to proceed via the renal system. Such brain uptake is better than that of currently used radiopharmaceuticals for brain imaging (99mTc-ECD and 99mTc-HMPAO). As a conclusion, EHPTIP is a newly synthesized dipeptide with a good antimicrobial activity and the radioiodinated EHPTIP which is labeled with 123I could be used as a novel agent for brain SPECT.