Synthesis of leading chalcones with high antiparasitic, against Hymenolepis nana, and antioxidant activities

The hymenolepiosis by Hymenolepis nana is a major public health problem in developing countries, and the commercial drugs against this parasitosis are not enough effective. The combination of antiparasitic and antioxidant agents has improved the treatment of some parasitoses. Thus, the development of new cestocidal and antioxidant agents to treat the hymenolepiosis cases is important. In the present study, four hydroxy- and four dihydroxy-chalcones were synthesized using the catalyst boron trifluoride diethyl etherate (BF3•OEt2). The antioxidant activity and antiparasitic against H. nana of chalcones were tested, as well as the toxicity by the brine shrimp lethality bioassay and the method of Lorke. The antioxidant activity was measured by three radical scavenging assays: 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP). The hydroxyl substitution pattern (number and position), mainly in ring B, was responsible for the chalcone antiparasitic activity. At least one meta or para hydroxyl group in ring B was essential for activity of the synthetic chalcones against H. nana; The time taken for the parasite to die by the 3b and 3e chalcones (20 mg/mL) treatment was up to six times lower than the control drug Praziquantel. On the other hand, chalcones with catechol structure in ring B (3g and 3h) showed the highest antioxidant values. The toxicity evaluations suggests that synthetic hydroxychalcones with cestocidal (3b and 3e) and antioxidant (3g and 3h) activities are safe compounds and potential in vivo agents to treat this parasitosis.

由微小膜壳绦虫（Hymenolepis nana）引发的膜壳绦虫病是发展中国家面临的主要公共卫生问题，现有针对该寄生虫病的商用药物疗效并不理想。抗寄生虫剂与抗氧化剂的联合应用已改善了部分寄生虫病的治疗方案，因此开发新型杀绦虫剂与抗氧化剂用于膜壳绦虫病的治疗具有重要意义。本研究以三氟化硼乙醚络合物（BF3•OEt2）为催化剂，合成了4种单羟基查尔酮与4种二羟基查尔酮。随后对这些查尔酮的抗氧化活性及抗微小膜壳绦虫活性进行了检测，并通过盐水虾致死性生物测定法与Lorke法评估了其毒性。抗氧化活性通过三种自由基清除实验进行测定：2,2'-联氮-双(3-乙基苯并噻唑啉-6-磺酸)（ABTS）、2,2-二苯基-1-苦基肼（DPPH）以及铁还原抗氧化能力（FRAP）实验。查尔酮的抗寄生虫活性主要受B环上羟基的取代模式（数量与位置）影响；B环上至少存在一个间位或对位羟基，是合成查尔酮具备抗微小膜壳绦虫活性的必要条件。经3b与3e号查尔酮（20 mg/mL）处理后，寄生虫的死亡时间相较于对照药物吡喹酮（Praziquantel）最高可缩短至原来的1/6。另一方面，B环具有邻苯二酚结构的查尔酮（3g与3h）展现出最高的抗氧化活性。毒性评估结果表明，兼具杀绦虫活性（3b、3e）与抗氧化活性（3g、3h）的合成羟基查尔酮安全性良好，是治疗该寄生虫病的潜在体内应用候选药物。