Synthesis,Characterization And In Vitro Evaluation Of L-Arginine-Based Curcumin

Curcumin（Cur）which widely present in the rhizomes of Zingiberaceae and Araceae plants,is mainly extracted and refined from the rhizomes of Turmeric.Curcumin has multiple pharmacological activities,and has low toxicity and good safety.However,its solubility in water is extremely poor（11 ng/m L）,which makes its bioavailability low and severely limits its development and application.In order to improve the solubility of curcumin,and increase its stability and bioavailability,a curcumin derivative（Cur-Sa-Arg）was prepared and synthesized through structural modification.Arginine（Arg）has the advantages of good water solubility and can participate in various physiological and biochemical reactions in organisms.It was hoped that these advantages could be used to improve curcumin’s defects.The main experimental contents were as follows:L-arginine based curcumin derivative with a succinic acidlinker（Cur-Sa-Arg）was synthesized via esterification and amidation reaction using 4-dimethylaminopyridine（DMAP）and 1-（3-dimethylaminopropyl）-3-ethylcarbodiimide（EDC）as catalyzer.The product was characterized by Fourier transform infrared spectroscopy（FT-IR）,hydrogen nuclear magnetic spectroscopy（¹H-NMR）,ultraviolet-visible spectrophotometry（UV-Vis）and differential scanning calorimetry（DSC）.FT-IR results confirmed the formation of ester and amide which formed in the process of the connection of curcumin with succinic anhydride and L-arginine.This FT-IR result and the results of ¹H-NMR,UV-Vis and DSC could jointly prove that Cur-Sa-Arg was successfully prepared.The solubility of Cur-Sa-Arg was 30.1μg/m L,which was about 3000 times higher than that of Cur,and the release rate in vitro was also significantly faster.Among them,the cumulative release of Cur-Sa-Arg in a buffer solution of p H 6.8 for 24h was the highest,which could reach 46.81%.Cur-Sa-Arg had good physical stability,but there was moisture absorption under 75%RH high humidity conditions,which reduced the effective content of curcumin.Compared with Cur,Cur-Sa-Arg had better stability in the solution with p H 1.2,p H 6.8 and p H 7.4.Cur-Sa-Arg and Cur were proven to have good antioxidant activity due to their excellent free radical scavenging ability.Cur-Sa-Arg showed stronger antibacterial activity than Cur in antibacterial experiments.The IC₅₀of Escherichia coli（E.coli）,Staphylococcus aureus（S.aureus）,Salmonella murine（S.murine）and Pseudomonas aeruginosa（P.aeruginosa）were 2-6 times smaller than Cur.The effects of Cur-Sa-Arg and Cur on the proliferation of human gastric cancer cells（MGC-803）,human cervical cancer cells（Hela）,and human breast cancer cells（MCF-7）were determined by MTT assay,and apoptotic cells were observed by inverted fluorescence microscope with PI and AO/EB dye staining.The results showed that Cur-Sa-Arg had a higher inhibitory effect on the above three kinds of tumor cells than Cur,and apoptotic tumor cells were significantly increased.And the cell scratch test showed that Cur-Sa-Arg had a significant inhibitory effect on the migration of MGC-803,MCF-7 and Hela cells.In summary,Cur-Sa-Arg could increase the solubility of curcumin,accelerate its dissolution and make it have better stability.Its antibacterial and antitumor activity had also been improved.This experiment provided experimental data support for the development and application of curcumin.