Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents
Synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents
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DOI：
10.1016/j.bmcl.2009.10.010
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发表时间：
2009-12-15
影响因子：
2.7
通讯作者：
Chauhan, Prem M. S.
中科院分区：
文献类型：
--
作者：
Kumar, Ashok;Srivastava, Kumkum;Chauhan, Prem M. S.
随着氯喹耐药性的广泛产生，合成成本有效的治疗疟疾的化疗药物具有挑战性和紧迫性。本文以廉价的6，9-二氯-2-甲氧基吖啶和三聚氯氰为原料，合成了一系列新型的9-苯胺基吖啶三嗪类化合物。本文报道了一系列新的杂合9-苯胺基吖啶三嗪类化合物对CQ敏感的3D 7株恶性疟原虫的体外抗疟活性和对VERO细胞的细胞毒性。在评价的化合物中，两种化合物17（IC 50 = 4.21 nM）和22（IC 50 = 4.27 nM）显示出比CQ（IC 50 = 8.15 nM）高两倍的效力。大多数化合物表现出相当高的选择性指数。化合物13和29以100 mg/kg剂量在瑞士小鼠中口服抗约氏疟原虫N-67株4天，分别显示> 96.59%和98.73%的抑制。(C)2009爱思唯尔有限公司保留所有权利。
There is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malaria after the widespread development of resistance to CQ. In the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines using the cheap chemicals 6,9-dichloro-2-methoxy acridine and cyanuric chloride. The series of new hybrid 9-anilinoacridine triazines were evaluated in vitro for their antimalarial activity against CQ-sensitive 3D7 strain of Plasmodium falciparum and their cytotoxicity were determined on VERO cell line. Of the evaluated compounds, two compounds 17 (IC50 = 4.21 nM) and 22 (IC50 = 4.27 nM) displayed two times higher potency than CQ (IC50 = 8.15 nM). Most of the compounds showed fairly high selectivity index. The compounds 13 and 29 displayed > 96.59% and 98.73% suppression, respectively, orally against N-67 strain of Plasmodium yoelii in swiss mice at dose 100 mg/kg for four days. (C) 2009 Elsevier Ltd. All rights reserved.