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

• Published in: BMC chemistry 2016-11, Vol.10 (1), p.73-73, Article 73
• Main Authors: Al-Wabli, Reem Ibrahim, Sakr, Tamer Mostafa Mohamed Hafez, Khedr, Mohammed Abdou, Selim, Adly Abdallah, El-Rahman, Mohamed Abd El-Motaleb Abd, Zaghary, Wafaa Abdou
• Format: Article
• Language: English
• Subjects: Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Nuclear medicine; Organic and Medicinal Chemistry; Radioisotopes; Research Article
• ISSN: 1752-153X; 1752-153X; 2661-801X
• DOI: 10.1186/s13065-016-0220-x

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 abstract This 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 99m Tc-curcumin derivative complex in solid tumor bearing Albino mice