以4-二甲氨基吡啶(DMAP)为催化剂,1-(3-二甲氨基丙基)-3-乙基碳二亚胺(EDC)为脱水剂,琥珀酸(Sa)为连接臂,通过酯化和酰胺化反应将姜黄素接枝到L-精氨酸分子上,获得新型L-精氨酸基姜黄素(Cur-Sa-Arg)衍生物,产物经UV-Vis、FT-IR、1H NMR和DSC表征,证明已成功合成.与姜黄素相比,Cur-Sa-Arg在水中的溶解度增大约3 000倍,达到30.1 μg/mL;对铜绿假单胞菌(Pseudomonas aeruginosa)、大肠杆菌(Escherichia coli)和鼠沙门氏菌(Salmonella ratus)等革兰氏阴性菌的抑菌IC50降低3~6倍,对革兰氏阳性菌中的金黄色葡萄球菌(Staphylococcus aureus)抑菌IC50降低2倍.结果表明,Cur-Sa-Arg可极大改善姜黄素水中溶解度,并且具有更优的抗菌性.
L-arginine based curcumin derivative with a succinic acid linker(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 UV-Vis, FT-IR, 1H NMR and DSC, and the results indicated that Cur-Sa-Arg was successfully synthesized. The curcumin solubility in Cur-Sa-Arg was more than about 3 000 times higher than curcumin and reached up to 30.1 μg/mL. Moreover, the result of bacteriostatic experiment showed that the IC50 values against Gram-negative bacteria including Pseudomonas aeruginosa, Escherichia coli and Salmonella ratus decreased by 3—6 times, and the IC50 value against Gram-positive bacteria of Staphylococcus aureus dropped by 2 times. Compared with pure curcumin, Cur-Sa-Arg has a higher solubility and better antibacterial properties.
[1] MOHANTY C, DAS M, SAHOO S K. Emerging role of nano-carriers to increase the solubility and bioavailability of Curcumin [J]. Expert Opinion on Drug Delivery, 2012, 9(11): 1347-1364. DOI: 10.1517/17425247.2012.724676.
[2] LOPRESTI, ADRIAN L. The problem of curcumin and its bioavail ability: could its gastrointestinal influence contribute to its overall health-enhancing effects? [J]. Advances in Nutrition, 2018, 9(1): 41-50. DOI: 10.1093/advances/nmx011.
[3] ODOT J, ALBERT P, CARLIER A, et al. In vitro and in vivo anti-tum oral effect of curcumin against melanom a cells [J]. International Journal of Cancer, 2004, 111(3): 381-387. DOI: 10.1002/ijc.20160.
[4] CHEN G, LI J, CAI Y, et al. A glycyrrhetinic acid-modified curcumin supramolecular hydrogel for liver tumor targeting therapy [J]. Scientific Reports, 2017, 7:44210. DOI: 10.1038/srep44210.
[5] PRASAD S, TYAGI A K, AGGARWAL B B. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice [J]. Cancer Research & Treatment, 2014, 46(1): 2-18. DOI: 10.4143/crt.2014.46.1.2.
[6] WANG L L, HE D D, WANG S X, et al. Preparation and evaluation of curcumin-loaded self-assembled micelles [J]. Drug Development and Industrial Pharmacy, 2018, 44(4): 563-569. DOI: 10.1080/03639045.2017.1405431.
[7] YANG W Z, WANG M M, MA L L, et al. Synthesis and characterization of biotin modified cholesteryl pullulan as a novel anticancer drug carrier [J]. Carbohydrate polymers, 2014, 99: 720-727. DOI: 10.1016/j.carbpol.2013.09.013.
[8] 杨文智,王树根,刘娇艳,等.透明质酸接枝普鲁兰糖的制备与表征 [J].河北大学学报(自然科学版),2017,37(2):141-146.DOI:10.3969/j.issn.1000-1565.2017.02.006.
[9] DUAN Y M, LI K Y, WANG H W, et al. Preparation and evaluation of curcumin grafted hyaluronic acid modified pullulan polymers as a functional wound dressing material [J]. Carbohydrate Polymers, 2020, 238: 116195. DOI: 10.1016/j.carbpol.2020.116195.
[10] 刘晓莹.姜黄素衍生物的合成表征及其生物活性研究 [D].福州:福建农林大学,2014.
[11] 蒋福升,徐秀玲,金波,等.水溶性姜黄素前药制备及其体外抗肿瘤实验研究 [J].中国药学杂志,2009,44(19):1492-1496.
[12] CUTRIGNELLI A, LOPEDOTA A, DENORA N, et al. A new complex of curcumin with sulfobutylether-β-cyclodextrinc:haracterization studies and in vitro evaluation of cytotoxic and antioxidant activity on hepG-2 Cells [J]. Journal of Pharmaceutical Sciences, 2014, 103(12): 3932-3940. DOI: 10.1002/jps.24200.
[13] MORAIS D D S, SIQUEIRA D D, LUNA C B B, et al. Grafting maleic anhydride onto polycaprolactone: influence of processing [J]. Materials Research Express, 2019, 6(5): 055315. DOI: 10.1088/2053-1591/ab050d.
[14] VAKAN S S, KAJWE A, SUVARNA V, et al. Influence of auxiliary agents on solubility and dissolution profile of repaglinide with hydroxypropyl-β-cyclodextrin: inclusion complex formation and its solid-state characterization [J]. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2015, 83(3-4): 239-250. DOI: 10.1007/s10847-015-0559-y.
[15] YANG R L, ZHANG S, KONG D L, et al. Biodegradable polymer-curcumin conjugate micelles enhance the loading and delivery of low-potency curcumin [J]. Pharmaceutical Research, 2012, 29: 3512-3525. DOI: 10.1007/s11095-012-0848-8.
[16] SARIKA P R, JAMES N R, NISHNA N, et al. Galactosylated pullulan-curcumin conjugate micelles for site specific anticanceractivity to hepatocarcinoma cells [J]. Colloids and Surfaces B: Biointerfaces, 2015, 133: 347-355. DOI: 10.1016/j.colsurfb.2015.06.020.
[17] BARDTS M, RITTER H. Novel copolymers showing interactions of amidinium-carboxylate groups in water [J]. Journal of Polymer Research, 2011, 18(1): 151-155. DOI: 10.1007/s10965-010-9401-9. GB/T 7714.
[18] AFFANDI R M M, MEOR M, TRIPATHY M, et al. Arginine complexes with simvastatin: apparent solubility, in vitro dissolution and solid state characterization [J]. Current Drug Delivery, 2018, 15(1): 77-86. DOI: 10.2174/1567201814666170320144259. (
