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Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity.

Khedr MA - Drug Des Devel Ther (2015)

Bottom Line: In silico study results showed the high binding affinity to lanosterol 14α-demethylase (-24.49 and -25.83 kcal/mol) for compounds V and VII, respectively; these values were greater than those for miconazole (-18.19 kcal/mol) and fluconazole (-16.08 kcal/mol).Compound V emerged as the most potent antifungal agent among all compounds with a half maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 µg/mL against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton rubrum, and Trichophyton mentagrophytes, respectively.The antifungal activity for most of the synthesized compounds was more potent than that of miconazole and fluconazole.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

ABSTRACT
Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14α-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were synthesized and evaluated for their antifungal activity. In silico study results showed the high binding affinity to lanosterol 14α-demethylase (-24.49 and -25.83 kcal/mol) for compounds V and VII, respectively; these values were greater than those for miconazole (-18.19 kcal/mol) and fluconazole (-16.08 kcal/mol). Compound V emerged as the most potent antifungal agent among all compounds with a half maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 µg/mL against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton rubrum, and Trichophyton mentagrophytes, respectively. The antifungal activity for most of the synthesized compounds was more potent than that of miconazole and fluconazole.

No MeSH data available.


Related in: MedlinePlus

Ramachandran plot for the homology model of Candida albicans L14αDM.
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f8-dddt-9-4501: Ramachandran plot for the homology model of Candida albicans L14αDM.

Mentions: The Ramachandran plot of the built model was generated and analyzed. Residues in the phi-psi core were 90%. Residues in the phi-psi enabled region were found to be 7%. Residues in omega core were found to be 96%, and in the omega enabled region, they were 3%. Conversely, residues in the omega generous region were 0%. The free energy of protein folding was computed and found to be −508.68 (Figure 8).


Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity.

Khedr MA - Drug Des Devel Ther (2015)

Ramachandran plot for the homology model of Candida albicans L14αDM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539092&req=5

f8-dddt-9-4501: Ramachandran plot for the homology model of Candida albicans L14αDM.
Mentions: The Ramachandran plot of the built model was generated and analyzed. Residues in the phi-psi core were 90%. Residues in the phi-psi enabled region were found to be 7%. Residues in omega core were found to be 96%, and in the omega enabled region, they were 3%. Conversely, residues in the omega generous region were 0%. The free energy of protein folding was computed and found to be −508.68 (Figure 8).

Bottom Line: In silico study results showed the high binding affinity to lanosterol 14α-demethylase (-24.49 and -25.83 kcal/mol) for compounds V and VII, respectively; these values were greater than those for miconazole (-18.19 kcal/mol) and fluconazole (-16.08 kcal/mol).Compound V emerged as the most potent antifungal agent among all compounds with a half maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 µg/mL against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton rubrum, and Trichophyton mentagrophytes, respectively.The antifungal activity for most of the synthesized compounds was more potent than that of miconazole and fluconazole.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

ABSTRACT
Fungal infections are a main reason for the high mortality rate worldwide. It is a challenge to design selective antifungal agents with broad-spectrum activity. Lanosterol 14α-demethylase is an attractive target in the design of antifungal agents. Seven compounds were selected from a number of designed compounds using a rational docking study. These compounds were synthesized and evaluated for their antifungal activity. In silico study results showed the high binding affinity to lanosterol 14α-demethylase (-24.49 and -25.83 kcal/mol) for compounds V and VII, respectively; these values were greater than those for miconazole (-18.19 kcal/mol) and fluconazole (-16.08 kcal/mol). Compound V emerged as the most potent antifungal agent among all compounds with a half maximal inhibitory concentration of 7.01, 7.59, 7.25, 31.6, and 41.6 µg/mL against Candida albicans, Candida parapsilosis, Aspergillus niger, Trichophyton rubrum, and Trichophyton mentagrophytes, respectively. The antifungal activity for most of the synthesized compounds was more potent than that of miconazole and fluconazole.

No MeSH data available.


Related in: MedlinePlus