Identification of novel antifungal agents: antimicrobial evaluation, SAR, ADME–Tox and molecular docking studies of a series of imidazole derivatives

BMC Chemistry

Btissam Bouchal¹  Mounia Elidrissi Errahhali¹  Manal Elidrissi Errahhali¹  Mohammed Bellaoui¹  Pierre H. Dixneuf²  Henri Doucet²  Rachid Touzani³  Farid Abrigach³  Abdelilah Takfaoui³ 

[1] Genetics Unit, Faculty of Medicine and Pharmacy of Oujda, University Mohammed Premier;Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS, Université de Rennes;Laboratory of Applied Chemistry & Environment, Faculty of Sciences, University Premier, Oujda, Morocco Mohamed Premier;

关键词: Imidazole;    Antifungal;    Antibacterial;    Structure–activity relationship;    ADME–Tox;    Docking;   

DOI  :  10.1186/s13065-019-0623-6

来源: DOAJ

【 摘 要 】

Abstract Thirty-four imidazole-based compounds synthesized by one-pot catalytic method were evaluated for their antifungal and antibacterial activities against several fungal and bacterial strains. None of the compounds had antibacterial activity. Interestingly, compounds 1, 2, 3, 10 and 15 displayed a strong antifungal activity against all the tested fungal species, while compounds 5, 7, 9, 11, 21 and 27 showed a moderate antifungal activity. To better understand the biological activity of the most active compounds ADME–Tox and molecular docking studies were carried out. Interestingly, compounds 1, 2, 3, 7, 10 and 15 showed excellent bioavailability. In addition, compounds 1, 2 and 3, exhibited good toxicity profiles. Docking studies of the two most active compounds 2 (IC50 of 95 ± 7.07 μM) and 10 (IC50 of 235 ± 7.07 μM) suggested that they might act by inhibiting the fungal lanosterol 14α-demethylase. Therefore, these novel antifungal agents merit further characterization for the development of new antifungal therapeutics.

【 授权许可】

Unknown