title: Synthesis and biological evaluation of the codrug of Leonurine and Aspirin as cardioprotective agents.
abstract: The novel codrugs of Leonurine and Aspirin, compounds 545 and 503 have been synthesized and evaluated on their cardioprotective effects. Preliminary pharmacological studies showed that both compounds 545 and 503 were able to increase cell viability of hypoxia-induced H9c2 cells, and compound 545 exhibited at least ten fold potency than 503 and their parent drugs (Leonurine and Aspirin). Further mechanisms studies indicated that the cardioprotective effect of 545 due to its (1) anti-oxidative ability by increasing SOD and CAT enzymes activity and decreasing MDA content and LDH leakage rate, (2) anti-apoptosis activity by regulating apoptosis-associated proteins expression during hypoxia, (3) anti-inflammatory effect by suppression of pro-inflammatory mediators. All of these results demonstrate that compound 545 as a new class of Leonurine analogue could be a drug candidate in our further drug development studies.
authors: Department of Medicinal Chemistry, School of Pharmacy, Jilin University, Changchun 130021, China; Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors: Huan
authors: H
authors: Gao
authors: Department of Medicinal Chemistry, School of Pharmacy, Jilin University, Changchun 130021, China.
authors: Xiaohong
authors: X
authors: Yang
authors: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: xfgu@fudan.edu.cn.
authors: Xianfeng
authors: X
authors: Gu
authors: Department of Pharmacology, School of Pharmacy and Institute of Biomedical Sciences, Fudan University, Shanghai 201203, China. Electronic address: zhuyz@fudan.edu.cn.
authors: Yi-Zhun
authors: YZ
authors: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; C013587:leonurine; D005707:Gallic Acid; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D001241:Aspirin
keywords: Aspirin; Cardioprotective agents; Leonruine