No abstract

Novel and facile synthesis of a triazole based bisconjugated triazaspirodecanone as a potential MRI contrast agent.

Rational design of a new class of MR (magnetic resonance) contrast agent for enhance relaxivity has been described. The click chemistry was employed to incorporate two moieties of 1‐(2‐methoxyphenyl)piperazine and serinol as a linker to enhance the affinity at the recognition sites. The designed ligand was attached to DO3A to synthesize DO3A‐serinol‐bis‐MPP (SBMPP) in 89 % yield. Gd‐DO3A‐SBMPP showed enhanced relaxivity r1 of 10.85±0.04 mM−1s−1 as compare to known gadolinium based contrast agents in clinics. The potentiometric titration of gadolinium loaded SBMPP exhibited strong selectivity for Gd3+ over physiological metal ions such as Zn2+ and Cu2+. Thus, the synthesis of bis‐conjugate could be observed as novel, instructive and initial proof of concept for the synthesis of MR contrast agent with enhanced relaxivity. The preliminary findings show the good biocompatibility and potential functionalities of MPP analogue to target brain regions through MRI.

Serotonin receptor subtypes are predominantly accountable for various neurophysiologic and cognitive processes and are expressed in the hippocampus region. SPECT based radioligands offer a cost effective understanding to the molecular changes which are used in the diagnoses of various neurological disorders. A Homobivalent approach was used to synthesize 1-(2-methoxyphenyl) piperazine based ligand by using click chemistry to incorporate two moieties of MPP via a linker (serinol) for SPECT (Single Photon Emission Computerised Tomography) evaluation. Molecular docking studies show better affinity for radiolabeled DO3 A-serinol-bis-MPP complex.The radiolabeling efficiency of conjugate was optimized and evaluated for stability by various parameters and was found to be 99 %. The complex shows appreciable brain uptake in rabbit. Ex Vivo pharmacology indicated approximately 50 % of the total brain uptake in the hippocampus region which showed the selective preference of the ligand for serotonin receptor. This study could be considered as a novel, informative and preclinical finding for using the synthesised 99m Tc-DO3 Aserinol-bis-MPP ligand to target serotonin receptor by SPECT imaging.