Study on the synthesis of novel Celecoxib derivatives and the cardiovascular risk
LIN Shan1 WANG Zeyu2 YANG Jianfeng1 ZONG Ming1 FAN Yuhua1 LI Sen1▲
1.School of Pharmacy, Daqing Campus, Harbin Medical University, Heilongjiang Province, Daqing 163319, China;
2.Research Institute of Chinese Medicine, University of Macao, Macao Special Administrative Region, Taipa 999078, China
Abstract：Objective To reduce the cardiovascular side effects of Celecoxib by modification structure. Methods Four novel derivatives of Celecoxib were synthesized via substitutions of Celecoxib-CF3 group. The structures were identified and determined by the data of LC-MS and NMR spectrum. A total of 36 Wistar rats with foot swelling induced by carrageen glue were randomly divided into 6 groups according to the weight, Celecoxib group (lavage given Celecoxib), compounds 1, 2, 3, 4 group (gastric gavage compounds 1-4) (a daily dose of 5 mg/kg, drug dispersed to 0.5 mL carboxymethyl cellulose sodium) , the control group (0.5 mL daily to sodium carboxy methyl cellulose) aqueous solution. Serum levels of cyclooxygenase-2 (COX-2) and inflammatory factor interleukin-6 (IL-6) were determined by enzyme-linked immunoadsorption assay (ELISA) on 3 days after treatment, and serum levels of clotting factors were determined on 7 days after treatment. Results Compared with Celecoxib group, there was no significant difference in COX-2 levels in the compound 1 group (P ＞ 0.05), while COX-2 levels in compound 2 to 4 group were increased (P ＜ 0.05). Compared with the Celecoxib group, there were no significant differences in IL-6 levels in the compounds 1 to 4 group (P ＞ 0.05). The clotting time of compounds 2 to 4 group was longer than that of celecoxib group (P ＜ 0.05). Conclusion Compounds 3 and 4 have similar effects to Celecoxib in inhibiting the inflammatory factor IL-6, however there is no significant effect on the clotting time of rats. Therefore, compounds 3 and 4 are expected to be Celecoxib-derived drug candidates with low cardiovascular risk.
林珊1 王泽雨2 杨建峰1 宗鸣1 范玉华1 李森1▲. 新型塞来昔布衍生物的合成及其心血管风险的研究[J]. 中国医药导报, 2020, 17(4): 8-13,27.
LIN Shan1 WANG Zeyu2 YANG Jianfeng1 ZONG Ming1 FAN Yuhua1 LI Sen1▲. Study on the synthesis of novel Celecoxib derivatives and the cardiovascular risk. 中国医药导报, 2020, 17(4): 8-13,27.
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2020, Vol. 17 
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