Acanthamoeba castellanii is a free-living amoeba which can cause a blinding keratitis and fatal granulomatous amoebic encephalitis. The treatment of Acanthamoeba infections is challenging due to formation of cyst. Quinazolinones are medicinally important scaffold against parasitic diseases. A library of nineteen new 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives was synthesized to evaluate their antiamoebic activity against Acanthamoeba castellanii. One-pot synthesis of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-ones (1-19) was achieved by reaction of 2-amino-4,5-dimethoxybenzoic acid, trimethoxymethane, and different substituted anilines. These compounds were purified and characterized by standard chromatographic and spectroscopic techniques. Antiacanthamoebic activity of these compounds was determined by amoebicidal, encystation, excystation and host cell cytopathogenicity in vitro assays at concentrations of 50 and 100 μg/mL. The IC50 was found to be between 100 and 50 μg/mL for all the compounds except compound 5 which did not exhibit amoebicidal effects at these concentrations. Furthermore, lactate dehydrogenase assay was also performed to evaluate the in vitro cytotoxicity of these compounds against human keratinocyte (HaCaT) cells. The results revealed that eighteen out of nineteen derivatives of quinazolinones significantly decreased the viability of A. castellanii. Furthermore, eighteen out of nineteen tested compounds inhibited the encystation and excystation, as well as significantly reduced the A. castellanii-mediated cytopathogenicity against human cells. Interestingly, while tested against human normal cell line HaCaT keratinocytes, all compounds did not exhibit any overt cytotoxicity. Furthermore, a detailed structure-activity relationship is also studied to optimize the most potent hit from these synthetic compounds. This report presents several potential lead compounds belonging to 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one derivatives for drug discovery against infections caused by Acanthamoeba castellanii.

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3-芳基-6,7-二甲氧基喹唑啉-4（3H）-一个文库对阿氏棘阿米巴的抗厌氧活性。

棘阿米巴棘阿米巴（Acanthamoeba castellanii）是一种自由生活的阿米巴，可引起致盲性角膜炎和致命的肉芽肿性阿米巴性脑炎。由于囊肿的形成，棘阿米巴感染的治疗具有挑战性。喹唑啉酮类药物是抗寄生虫病的重要医学支架。合成了十九个新的3-芳基-6,7-二甲氧基喹唑啉-4（3H）-一衍生物的文库，以评估其对卡氏棘阿米巴的抗阿米巴活性。通过2-氨基-4,5-二甲氧基苯甲酸，三甲氧基甲烷和不同的取代苯胺反应，一锅合成3-芳基-6,7-二甲氧基喹唑啉-4（3H）-（1-19）。通过标准色谱和光谱技术对这些化合物进行纯化和表征。通过阿米巴杀菌剂，抑菌剂，浓度为50和100μg/ mL的体外兴奋试验和宿主细胞的细胞致病性。对于除了在这些浓度下不表现出杀螨作用的化合物5以外的所有化合物，发现IC 50为100至50μg/ mL。此外，还进行了乳酸脱氢酶测定，以评估这些化合物对人角质形成细胞（HaCaT）细胞的体外细胞毒性。结果显示，喹唑啉酮的十九种衍生物中有十八种显着降低了Castellanii的活力。此外，在19种测试化合物中，有18种抑制了侵入和兴奋，并显着降低了卡氏杆菌介导的针对人类细胞的细胞致病性。有趣的是，在针对人类正常细胞系HaCaT角质形成细胞进行测试时，所有化合物均未显示任何明显的细胞毒性。此外，还研究了详细的构效关系，以优化这些合成化合物的最有效命中率。该报告提出了属于3-芳基-6,7-二甲氧基喹唑啉-4（3H）-one衍生物的几种潜在的先导化合物，用于发现针对卡氏棘阿米巴引起的感染的药物。