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Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity
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 desig...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539092/ https://www.ncbi.nlm.nih.gov/pubmed/26309398 http://dx.doi.org/10.2147/DDDT.S84178 |
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author | Khedr, Mohammed A |
author_facet | Khedr, Mohammed A |
author_sort | Khedr, Mohammed A |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4539092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45390922015-08-25 Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity Khedr, Mohammed A Drug Des Devel Ther Original Research 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. Dove Medical Press 2015-08-10 /pmc/articles/PMC4539092/ /pubmed/26309398 http://dx.doi.org/10.2147/DDDT.S84178 Text en © 2015 Khedr. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Khedr, Mohammed A Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity |
title | Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity |
title_full | Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity |
title_fullStr | Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity |
title_full_unstemmed | Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity |
title_short | Stepwise design, synthesis, and in vitro antifungal screening of (Z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity |
title_sort | stepwise design, synthesis, and in vitro antifungal screening of (z)-substituted-propenoic acid derivatives with potent broad-spectrum antifungal activity |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539092/ https://www.ncbi.nlm.nih.gov/pubmed/26309398 http://dx.doi.org/10.2147/DDDT.S84178 |
work_keys_str_mv | AT khedrmohammeda stepwisedesignsynthesisandinvitroantifungalscreeningofzsubstitutedpropenoicacidderivativeswithpotentbroadspectrumantifungalactivity |