Abstract
Background Persistent inflammation might induce lipid metabolism disorders, which affected a significant proportion of the population worldwide, such as serious infections, cardiovascular diseases and autoimmune diseases. 14-Alpha-Lipoic acylandrographolide (AL-1) was previously synthesized and shown good activity to treat inflammatory diseases
in our lab. However, AL-1 has a poor solubility in water and hygroscopicity, which brings problems in drug delivery.
Aim To enhance the water solubility of AL-1 and its anti-inflammatory activity.
Method By modifying its structure, we designed and synthesized the andrographolide derivative hydrochloric salt AL-2, which contains two glycine groups compared with AL-1. Then, the anti-inflammatory activity of AL-2 was evaluated in vitro.
Results and Conclusions Both AL-1 and AL-2 could inhibit the release of NO in inflammatory cells. In addition, the water-solubility of AL-2 was improved as well as its cytotoxicity was reduced. Therefore, these results suggested that AL-2 may be a potential drug candidate in the treatment of inflammation.
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References
Kawalec P, Pilc A. An indirect comparison of infliximab versus adalimumab or golimumab for active ulcerative colitis. Arch Med Sci. 2016;12:1097–1109.
Ramadass SK, Jabaris SL, Perumal RK, HairulIslam VI, Gopinath A, Madhan B. Type I collagen and its daughter peptides for targeting mucosal healing in ulcerative colitis: A new treatment strategy. Eur J Pharm Sci. 2016;91:216–24.
Lindblom R, Higgins G, Coughlan M, de Haan JB. Targeting mitochondria and reactive oxygen species-driven pathogenesis in diabetic nephropathy. Rev Diabet Stud. 2015;12:134–56.
Romero-Castro A, Gutierrez-Sanchez M, Correa-Basurto J, Rosales Hernández MC, Padilla M, Mendieta-Wejebe JE. Pharmacokinetics in wistar rats of 5-[(4-carboxybutanoyl) amino]-2-hydroxybenzoic acid: a novel synthetic derivative of 5-aminosalicylic acid (5-ASA) with possible anti-inflammatory activity. PLoS One. 2016;11:e0159889.
Wang Z, Yu P, Zhang G, Xu L, Wang D, Wang L, et al. Design, synthesis and antibacterial activity of novel andrographolide derivatives. Bioorg Med Chem. 2010;18:4269–74.
Zhu YY, Yu G, Zhang Y, Xu Z, Wang YQ, Yan GR, et al. A novel andrographolide derivative AL-1 exerts its cytotoxicity on K562 cells through a ROS-dependent mechanism. Proteomics. 2013;13:169–78.
Li Y, Yan H, Zhang Z, Zhang G, Sun Y, Yu P, et al. Andrographolide derivative AL-1 improves insulin resistance through down-regulation of NF-?B signalling pathway. Br J Pharmacol. 2015;172:3151–8.
Jiang X, Yu P, Jiang J, Zhang Z, Wang Z, Yang Z, et al. Synthesis and evaluation of antibacterial activities of andrographolide analogues, Eur J Med Chem. 2009;44:2936–43.
Yang Y, Yan H, Jing M, Zhang Z, Zhang G, Sun Y, et al. Andrographolide derivative AL-1 ameliorates TNBS-induced colitis in mice: involvement of NF-?B, and PPAR-? signaling pathways. Sci Rep. 2016;6:29716.
Muenster U, Mueck W, van der Mey D, Schlemmer KH, Greschat-Schade S, Haerter M, et al. Predicting biopharmaceutical performance of oral drug candidates - Extending the volume to dissolve applied dose concept. Eur J Pharm Biopharm. 2016;102:191–201.
Tilborg A, Norberg B, Wouters J. Pharmaceutical salts and cocrystals involving amino acids: a brief structural overview of the state-of-art. Eur J Med Chem. 2014;74:411–26.
Yao H, Li S, Yu P, Tang X, Jiang J, Wang Y. Reaction characteristics of andrographolide and its analogue AL-1 with GSH, as a simple chemical simulation of NF-?B inhibition, Molecules. 2012;17:728–39.
Fini A, Cavallari C, Bassini G, Ospitali F, Morigi R. Diclofenac salts, part 7: are the pharmaceutical salts with aliphatic amines stable?. J Pharm Sci. 2012;101:3157–68.
Xu R, Wang J, Du C, Han S, Meng L, Zhao H. Solubility determination and thermodynamic dissolution functions of 1,3-diphenylguanidine in nine organic solvents at evaluated temperatures. The Journal of Chemical Thermodynamics. 2016;99:86–95.
Cong Y, Wang J, Du C, Han S, Zhao H. Solubility and solution thermodynamics of 2-methyl-6-nitroaniline in ten organic solvents at elevated temperatures. The Journal of Chemical Thermodynamics. 2016;101:180-9.
Coneski PN, Schoenfisch MH. Nitric oxide release: part III. Measurement and reporting. Chem Soc Rev. 2012;41:3753–8.
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