Amodiaquine is a 4-aminoquinoline compound primarily used for the treatment of malaria, and also possesses anti-inflammatory and antiviral effects[1]. Amodiaquine is a nuclear receptor Nurr1 agonist with an EC50 value of approximately 20μM[2]. Amodiaquine is a histamine N-methyltransferase inhibitor[3].
In vitro, treatment of primary CD4+ T cells isolated from mouse lymph nodes and spleen with Amodiaquine (10µM) for 24h and 48h inhibited the proliferation of Th1, Th2, Th17, and Treg cells induced by different exogenous cytokines and promoted T cell apoptosis[4]. Pretreatment of HKC-8 cells with Amodiaquine (10µM) for 1h improved the functional mitochondrial quality and the balance of mitochondrial fusion/fission protein expression[5].
In vivo, Amodiaquine (20mg/kg) administered intraperitoneally every other day for 14 weeks to diabetic mice effectively reduced proteinuria and histopathological changes in the kidneys of diabetic mice and increased the activity of 5′AMP-activated protein kinase (AMPK) in the kidneys[5]. Amodiaquine (40mg/kg) administered intraperitoneally three times in total (at 3h after induction of ICH and then daily at a 24-h interval) to mice with intracerebral hemorrhage (ICH), effectively reduced the activation of microglia/macrophages and astrocytes around the hematoma, inhibited the mRNA expression of ICH-induced IL-1β, CCL2 and CXCL2, and improved motor dysfunction in mice[6].
References:
[1] Romero A H, Delgado F. 4-Aminoquinoline as a privileged scaffold for the design of leishmanicidal agents: structure–property relationships and key biological targets[J]. Frontiers in Chemistry, 2025, 12: 1527946.
[2] Sai M, Hank E C, Tai H M, et al. Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing[J]. Communications Chemistry, 2024, 7(1): 149.
[3] Horton J R, Sawada K, Nishibori M, et al. Structural basis for inhibition of histamine N-methyltransferase by diverse drugs[J]. Journal of molecular biology, 2005, 353(2): 334-344.
[4] Oh S, Shin J H, Jang E J, et al. Anti-inflammatory activity of chloroquine and amodiaquine through p21-mediated suppression of T cell proliferation and Th1 cell differentiation[J]. Biochemical and biophysical research communications, 2016, 474(2): 345-350.
[5] Jeong H Y, Kang J M, Jun H H, et al. Chloroquine and amodiaquine enhance AMPK phosphorylation and improve mitochondrial fragmentation in diabetic tubulopathy[J]. Scientific Reports, 2018, 8(1): 8774.
[6] Kinoshita K, Matsumoto K, Kurauchi Y, et al. A Nurr1 agonist amodiaquine attenuates inflammatory events and neurological deficits in a mouse model of intracerebral hemorrhage[J]. Journal of Neuroimmunology, 2019, 330: 48-54.
Amodiaquine是一种4-氨基喹啉类化合物，主要用于疟疾的治疗，还具有抗炎、抗病毒作用[1]。Amodiaquine是一种核受体Nurr1激动剂，EC50值约为20μM[2]。Amodiaquine是一种组胺N-甲基转移酶抑制剂[3]。
在体外，Amodiaquine（10µM）处理从小鼠淋巴结和脾脏中分离的原代CD4+ T 细胞24h和48h，抑制了不同外源性细胞因子诱导的Th1、Th2、Th17和Treg细胞的增殖，促进了T细胞凋亡[4]。Amodiaquine（10µM）预处理HKC-8细胞1h，改善了细胞的功能性线粒体质量和线粒体融合/分裂蛋白表达的平衡[5]。
在体内，Amodiaquine（20mg/kg）每隔一天通过腹腔注射给药治疗糖尿病小鼠14周，有效减轻了糖尿病小鼠肾脏的蛋白尿和组织病理学改变，增加了肾脏中5′AMP激活蛋白激酶（AMPK）的活性[5]。Amodiaquine（40mg/kg，3次，首次给药是在诱导脑出血后3小时，之后每隔24小时给药一次）通过腹腔注射给药治疗脑内出血（ICH）小鼠，减少了小胶质细胞/巨噬细胞和星形胶质细胞的血肿周围活化，抑制了ICH诱导的IL-1β、趋化因子2（CCL2）和C-X-C基序趋化因子配体2（CXCL2）的mRNA表达，并改善了小鼠的运动功能障碍[6]。