数字中医药（英文）2021，Vol.4Issue(4)：290-304,15.DOI:10.1016/j.dcmed.2021.12.004
新型N-(2-芳基氨基苯基)-2,3-二苯基喹喔啉-6-磺胺类药物作为潜在抗疟疾、抗真菌和抗细菌药物的合理药物设计、合成和生物学评价
Rational drug design, synthesis, and biological evaluation of novel N-(2-arylaminophenyl)-2,3-diphenylquinoxaline-6-sulfonamides as potential antimalarial, antifungal, and antibacterial agents
Ahmed Hassen Shntaif 1Sharuk Khan 2Ganesh Tapadiya 3Anand Chettupalli 4Shweta Saboo 5Mohd Sayeed Shaikh 3Falak Siddiqui 2Ramkoteswra Rao Amara6
作者信息
- 1. College of Science for Women,Babylon University,Hilla,Babil 00964,Iraq
- 2. MUPs College of Pharmacy (B Pharm),Washim,Maharashtra 444506,India
- 3. Shreeyash Institute of Pharmaceutical Education and Research,Aurangabad,Maharashtra 431010,India
- 4. Department of Pharmaceutical Sciences,Center for Nanomedicine,Anurag University,Hyderabad 501301,India
- 5. Government College of Pharmacy,Karad,Maharashtra 415124,India
- 6. Department of Pharmacy,Shri Jagdishprasad Jhabarmal Tibrewala University,Vidya Nagari,Rajasthan 333001,India
- 折叠
摘要
Abstract
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.关键词
磺胺类/抗疟药/抗真菌/抗细菌/疟原虫半胱氨酸蛋白酶falcipain-2/2,3-二苯基喹喔啉/恶性疟原虫Key words
Sulfonamides/Antimalarials/Antifungal/Antibacterial/Plasmodium cysteine protease falcipain-2/2,3-Diphenylquinoxaline-6-sulfonamide/Plasmodium falciparum引用本文复制引用
Ahmed Hassen Shntaif,Sharuk Khan,Ganesh Tapadiya,Anand Chettupalli,Shweta Saboo,Mohd Sayeed Shaikh,Falak Siddiqui,Ramkoteswra Rao Amara..新型N-(2-芳基氨基苯基)-2,3-二苯基喹喔啉-6-磺胺类药物作为潜在抗疟疾、抗真菌和抗细菌药物的合理药物设计、合成和生物学评价[J].数字中医药（英文）,2021,4(4):290-304,15.
