Imidazole derivatives as antiparasitic agents and use of molecular modeling to investigate the structure-activity relationship

被引:27
作者
Adeyemi, Oluyomi Stephen [1 ,2 ]
Eseola, Abiodun Omokehinde [3 ,4 ]
Plass, Winfried [3 ]
Atolani, Olubunmi [5 ]
Sugi, Tatsuki [6 ]
Han, Yongmei [6 ,7 ]
Batiha, Gaber El-saber [6 ,8 ,9 ]
Kato, Kentaro [6 ,10 ]
Awakanl, Oluwakemi Josephine [11 ]
Olaolu, Tomilola Debby [11 ]
Nwonuma, Charles Obiora [11 ]
Alejolowo, Omokolade [11 ]
Owolabi, Akinyomade [12 ]
Rotimi, Damilare [11 ]
Kayode, Omowumi Titilola [11 ]
机构
[1] Ton Duc Thang Univ, Lab Theoret & Computat Biophys, Ho Chi Minh City, Vietnam
[2] Ton Duc Thang Univ, Fac Appl Sci, Ho Chi Minh City, Vietnam
[3] Friedrich Schiller Univ Jena, Inst Inorgan & Analyt Chem, Humboldtstr 8, D-07743 Jena, Germany
[4] Redeemers Univ, Dept Chem Sci, Ede, Nigeria
[5] Univ Ilorin, Dept Chem, PMB 1515, Ilorin, Nigeria
[6] Obihiro Univ Agr & Vet Med, Natl Res Ctr Protozoan Dis, Inada Cho, Obihiro, Hokkaido 0808555, Japan
[7] Inner Mongolia Univ, Nationalities Coll Anim Sci & Technol, Tongliao, Inner Mongolia, Peoples R China
[8] Damanhour Univ, Fac Vet Med, Dept Pharmacol, Damanhour, Egypt
[9] Damanhour Univ, Fac Vet Med, Therapeut Dept, Damanhour, Egypt
[10] Tohoku Univ, Grad Sch Agr Sci, Lab Sustainable Anim Environm, 232-3 Yomogida, Osaki, Miyagi 9896711, Japan
[11] Landmark Univ, Dept Biochem, Med Biochem Nanomed & Toxicol Lab, PMB 1001, Omu Aran 251101, Nigeria
[12] Landmark Univ, Dept Microbiol, PMB 1001, Omu Aran 251101, Nigeria
关键词
Drug discovery; Infectious diseases; Medicinal biochemistry; Medicinal chemistry; CHIH-DFT DETERMINATION; TOXOPLASMA-GONDII; DRUG DISCOVERY; INORGANIC NANOPARTICLES; ESTIMATE SOLUBILITY; PERMEABILITY; COMPOUND;
D O I
10.1007/s00436-020-06668-6
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1-8), phenyl-substituted 1H-imidazoles (compounds 9-19), and thiopene-imidazoles (compounds 20-26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure-activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity (> 1176 to > 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism.
引用
收藏
页码:1925 / 1941
页数:17
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