Issue 9, 2016

Synthesis, preclinical evaluation and molecular modelling of macrocyclic appended 1-(2-methoxyphenyl)piperazine for 5-HT1A neuroreceptor imaging

Abstract

5-HT1A receptors are known to be implicit in a number of neuropsychiatric fluctuations related to mood and anxiety. Their visualization in the human brain using PET, SPECT or MRI is of great importance in the management and treatment of neurological disorders. The present work focuses on the metal complexes (Gd3+, Eu3+ and Ga3+) of DO3A-butyl-MPP to be used as brain (cerebral cortex, hippocampus, and amygdala) imaging agents using different modalities. Synthesis of 2,2′,2′′-(10-(2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DO3A-butyl-MPP) was achieved by conjugating the chloroacetylated derivative of 1-(2-methoxyphenyl)piperazine-butylamine with trisubstituted cyclen with subsequent cleavage with trifluoroacetic acid (TFA). The resulting compound was then labeled with GdCl3 and 68GaCl3 to perform MRI (relaxivity studies) and PET respectively. The longitudinal relaxivity (r1), and transverse relaxivity (r2), were determined to be 6.66 and 11.486 mM−1 s−1 respectively on 7 T at 21 °C. The SD (Sprague Dawley) rat brain uptake was 3.91% ID per g (percentage of the injected dose per gram) at 30 min post injection. Homology modeling and docking studies at the shallow antagonist binding pocket of 5-HT1A show a high G score of −12.132 that confers high binding of the ligand at the target receptor.

Graphical abstract: Synthesis, preclinical evaluation and molecular modelling of macrocyclic appended 1-(2-methoxyphenyl)piperazine for 5-HT1A neuroreceptor imaging

Supplementary files

Article information

Article type
Paper
Submitted
09 Jul 2015
Accepted
06 Jan 2016
First published
18 Jan 2016

RSC Adv., 2016,6, 7288-7301

Author version available

Synthesis, preclinical evaluation and molecular modelling of macrocyclic appended 1-(2-methoxyphenyl)piperazine for 5-HT1A neuroreceptor imaging

P. P. Hazari, S. Prakash, V. K. Meena, N. Singh, K. Chuttani, N. Chadha, P. Singh, S. Kukreti and A. K. Mishra, RSC Adv., 2016, 6, 7288 DOI: 10.1039/C5RA13432C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements