Modified benzoxazolone (ABO‐AA) based single photon emission computed tomography (SPECT) probes for 18 kDa translocator protein. Issue 6 (11th June 2019)

• Record Type: Journal Article
• Authors: Srivastava, Pooja; Kakkar, Dipti; Kumar, Pravir; Tiwari, Anjani Kumar
• Is Part Of: Drug development research. Volume 80:Issue 6(2019)
• Page Start: 741
• Page End: 749
• Publication Date: 2019-06-11
• Subjects: acetamidobenzoxazolone -- inflammation -- SPECT -- tryptophan methyl ester -- TSPO; Drug development -- Periodicals; Drugs -- Research -- Periodicals; 615.19
• DOI: 10.1002/ddr.21547
• Languages: English
• ISSNs: 0272-4391

Abstract

Abstract: Acetamidobenzoxazolone (ABO) has been modified to ABO‐AA, 2‐(2‐(5‐bromo/chloro benzoxazolone)acetamide)‐3‐(1 H ‐indol‐3‐yl)propionate to improve pharmacokinetics and lipophilicity (log p = 2.04). The final compound was synthesized in better yield and in fewer steps than previously reported MBIP‐Br (70% vs. 62%). Computational docking confirmed binding of MBIP‐Cl with translocator protein (TSPO) as well as with mutant TSPO (−8.99 for PDB: 4RYQ and −9.30 for PDB: 4UC1, respectively). Ex‐vivo biodistribution and scintigraphy showed that 99m Tc‐MBIP‐Cl is better than 99m Tc‐MBIP‐Br in terms of uptake in TSPO‐rich organs and release kinetics 0–120 min postinjection. At 15 min, uptake was 2.75‐fold (12.91%ID/g vs. 4.69%ID/g) in lung and seven‐fold (5.16%ID/g vs. 0.72%ID/g) in heart for 99m Tc‐MBIP‐Cl compared to that of 99m Tc‐MBIP‐Br which gives warrant to utilize this single photon emission computed tomography agent in higher animals.