1-Aryl-3-(1H-imidazol-1-yl)propan-1-ol esters: synthesis, anti-Candida potential and molecular modeling studies

Chemistry Central Journal

Mohamed I Attia¹  Awwad A Radwan²  Azza S Zakaria³  Maha S Almutairi⁴  Soraya W Ghoneim⁴ 

[1] Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, 12622, Dokki, Giza, Egypt

[2] Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71527, Egypt

[3] Department of Microbiology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

[4] Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

关键词: Molecular modeling;    Anti-Candida;    Esters;    Imidazole;    Mannich reaction;    Synthesis;   

Others  :  787826
DOI  :  10.1186/1752-153X-7-168

 received in 2013-08-11, accepted in 2013-10-18,  发布年份 2013

【 摘 要 】

Background

An increased incidence of fungal infections, both invasive and superficial, has been witnessed over the last two decades. Candida species seem to be the main etiology of nosocomial fungal infections worldwide with Candida albicans, which is commensal in healthy individuals, accounting for the majority of invasive Candida infections with about 30-40% of mortality.

Results

New aromatic and heterocyclic esters 5a-k of 1-aryl-3-(1H-imidazol-1-yl)propan-1-ols 4a-d were successfully synthesized and evaluated for their anti-Candida potential. Compound 5a emerged as the most active congener among the newly synthesized compounds 5a-k with MIC value of 0.0833 μmol/mL as compared with fluconazole (MIC value >1.6325 μmol/mL). Additionally, molecular modeling studies were conducted on a set of anti-Candida albicans compounds.

Conclusion

The newly synthesized esters 5a-k showed more potent anti-Candida activities than fluconazole. Compounds 7 and 8 revealed significant anti-Candida albicans activity and were able to effectively satisfy the proposed pharmacophore geometry, using the energy accessible conformers (E_conf < 20 kcal/mol).

【 授权许可】

   
2013 Attia et al.; licensee Chemistry Central Ltd.

【 图 表 】

Figure 1.

Scheme 1

Scheme 2

Figure 2.

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