Platelet-12 lipoxygenase targeting via a newly synthesized curcumin derivative radiolabeled with technetium-99m

Reem Ibrahim Al-Wabli; Tamer Mostafa Mohamed Hafez Sakr; Mohammed Abdou Khedr; Adly Abdallah Selim; Mohamed Abd El-Motaleb Abd El-Rahman; Wafaa Abdou Zaghary

doi:10.1186/s13065-016-0220-x

Platelet-12 lipoxygenase targeting via a newly synthesized curcumin derivative radiolabeled with technetium-99m

Chem Cent J. 2016 Nov 28:10:73. doi: 10.1186/s13065-016-0220-x. eCollection 2016.

Authors

Reem Ibrahim Al-Wabli¹, Tamer Mostafa Mohamed Hafez Sakr², Mohammed Abdou Khedr³, Adly Abdallah Selim⁴, Mohamed Abd El-Motaleb Abd El-Rahman⁴, Wafaa Abdou Zaghary³

Affiliations

¹ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451 Saudi Arabia.
² Radioactive Isotopes and Generator Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
³ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, 11795 Egypt.
⁴ Labeled Compounds Department, Hot Labs Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.

Abstract

Background: One of the most popular techniques for cancer detection is the nuclear medicine technique. The present research focuses on Platelet-12-lipoxygenase (P-12-LOX) as a promising target for treating and radio-imaging tumor tissues. Curcumin was reported to inhibit this enzyme via binding to its active site.

Results: A novel curcumin derivative was successfully synthesized and characterized with yield of 74%. It was radiolabeled with the diagnostic radioisotope technetium-99m with 84% radiochemical yield and in vitro stability up to 6 h. The biodistribution studies in tumor bearing mice confirmed the high affinity predicted by the docking results with a free binding energy value of (ΔG -50.10 kcal/mol) and affinity (13.64 pki) showing high accumulation in solid tumor with target/non-target ratio >6.

Conclusion: The newly synthesized curcumin derivative, as a result of a computational study on platelet-12 lipoxygenase, showed its excellent free binding energy (∆G -50.10 kcal/mol) and high affinity (13.64 pKi). It could be an excellent radio-imaging agent that targeting tumor cells via targeting of P-12-LOX.Graphical abstractThis novel curcumin derivative was successfully synthesized and radiolabeled with technetium-99m and biologically evaluated in tumor bearing mice that showed high accumulation in solid tumor with target/non-target ratio >6 confirming the affinity predicted by the docking results. Predicted binding mode of a new curcumin derivative in complex with 12-LOX active site. b Curcumin itself in the 12-LOX active site biological distribution of ^99mTc-curcumin derivative complex in solid tumor bearing Albino mice.

Keywords: Cancer imaging; Curcumin; Docking; Enzyme targeting; Platelet-12 lipoxygenase; Technetium-99m.