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目的 磺胺、磺胺嘧啶和氨苯砜是第一批通过破坏叶酸生物合成过程来治疗疟疾的磺胺类药物,叶酸生物合成过程是寄生虫存活的关键.因此,我们旨在通过合理的药物设计方法合成新型N-(2-芳基氨基苯基)-2,3-二苯基喹喔啉-6-磺酰胺衍生物.方法 按常规方法合成所有化合物,并用光谱分析(1H核磁共振和质谱)对产物进行表征.使用薄层色谱法(TLC)监测反应进程.分析了所有衍生物在疟原虫半胱氨酸蛋白酶falcipain-2变构位点的有效结合模式.采用肉汤稀释法测定抗菌和抗真菌活性.结果 S6(N-(2-噻唑-4-基)-乙酰基-氨基苯基)-2,3-二苯基喹喔啉-6-磺酰胺与S9(N-(1H-苯并[d]咪唑-2-基)氨基苯基)-2,3-二苯基喹喔啉-6-磺酰胺形成5个氢键;S8(N-(2-1H-咪唑-2-基)氨基苯基)-2,3-二苯基喹喔啉-6-磺酰胺和S10(N-(1-苯并[d]咪唑-5-基)氨基苯基)-2,3-二苯基喹喔啉-6-磺酰胺与酶的变构位点形成四个氢键.考虑到与目标酶的对接分数和氢键的形成,新的衍生物被加工用于湿实验室合成.所有新合成的衍生物都具有体外抗疟疾、抗真菌和抗菌活性.与标准品相比,所有衍生物对恶性疟原虫株表现出足够的敏感性.此外,化合物S9和S10显示出最有效的双重抗微生物和抗疟疾活性.它们在分子对接研究中也显示出强大的分子相互作用.结论 基于以上结果,我们认为N-(2-芳基氨基苯基)-2,3-二苯基喹喔啉-6-磺酰胺衍生物具有作为抗疟药、抗真菌药和抗菌剂的优异生物潜力.“,”Objective Sulfanilamide, sulfadiazine, and dapsone were the first sulfonamides to be used to treat malaria by disrupting the folate biosynthesis process, which is essential for parasite survival. Therefore, we aimed to synthesize novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives through a ra-tional drug design approach. Methods All compounds were synthesized by the conventional method, and the products were characterized by spectral analysis (1H NMR and mass spectrometry). The progression of the reac-tion was monitored using thin-layer chromatography (TLC). All the derivatives were analyzed for their effective binding mode in the allosteric site of the plasmodium cysteine protease falcipain-2. Antibacterial and antifungal activities were determined using the broth dilution method. Results S6 (N-(2-thiazol-4yl)-acetyl-aminophenyl)-2,3-diphen-ylquinoxaline-6-sulfonamideand S9 (N-(1H-benzo[d]imidazol-2-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide formed five hydrogen bonds; S8 (N-(2-1H-imidazol-2yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide and S10 (N-(1H-benzo[d] imidazol-5-yl)aminophenyl)-2,3-diphenylquinoxaline-6-sulfon-amide formed four hydrogen bonds with the allosteric site of the enzyme. Considering the docking scores and formation of hydro-gen bonds with the target enzyme, the novel derivatives were pro-cessed for wet lab synthesis. All the newly synthesized derivatives were subjected to in vitro antimalarial, antifungal, and antibac-terial activities. All the derivatives exhibited sufficient sensitivity to the Plasmodium falciparum strain compared to the standards. Moreover, compounds S9 and S10 showed the most potent dual antimicrobial and antimalarial activities. They also exhibited powerful molecular interactions in molecular docking studies.Conclusion Based on the above results, it was concluded that N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamide derivatives have excellent biological potential to act as antimal-arial, antifungal, and antibacterial agents.