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Synthesis, structure optimization and antifungal screening of novel tetrazole ring bearing acyl-hydrazones.

Malik MA, Al-Thabaiti SA, Malik MA - Int J Mol Sci (2012)

Bottom Line: Propidium iodide rapidly penetrated a majority of yeast cells when they were treated with the synthesized compounds at concentrations just above MIC, implying that fungicidal activity resulted from extensive lesions of the plasma membrane.Target compounds also caused a considerable reduction in the amount of ergosterol.The results also showed that the presence and position of different substituents on the phenyl ring of the acylhydrazone pendant seem to play a role on the antifungal activity as well as in deciding the fungistatic and fungicidal nature of the compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21413, Saudi Arabia; E-Mail: sthabaiti@kau.edu.sa.

ABSTRACT
Azoles are generally fungistatic, and resistance to fluconazole is emerging in several fungal pathogens. In an attempt to find novel azole antifungal agents with improved activity, a series of tetrazole ring bearing acylhydrazone derivatives were synthesized and screened for their in vitro antifungal activity. The mechanism of their antifungal activity was assessed by studying their effect on the plasma membrane using flow cytometry and determination of the levels of ergosterol, a fungal-specific sterol. Propidium iodide rapidly penetrated a majority of yeast cells when they were treated with the synthesized compounds at concentrations just above MIC, implying that fungicidal activity resulted from extensive lesions of the plasma membrane. Target compounds also caused a considerable reduction in the amount of ergosterol. The results also showed that the presence and position of different substituents on the phenyl ring of the acylhydrazone pendant seem to play a role on the antifungal activity as well as in deciding the fungistatic and fungicidal nature of the compounds.

No MeSH data available.


Related in: MedlinePlus

Laser confocal images of Candida cells. Cells with membrane damage are seen stained with PI (red signals).
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f1-ijms-13-10880: Laser confocal images of Candida cells. Cells with membrane damage are seen stained with PI (red signals).

Mentions: Candida cells were grown and then stained with propidium iodide (PI) as described in materials and methods. PI penetrates only those cells which have severe membrane lesions; the entire yeast cell appears red. The laser confocal images of stained Candida cells exposed to test compounds are shown in Figure 1.


Synthesis, structure optimization and antifungal screening of novel tetrazole ring bearing acyl-hydrazones.

Malik MA, Al-Thabaiti SA, Malik MA - Int J Mol Sci (2012)

Laser confocal images of Candida cells. Cells with membrane damage are seen stained with PI (red signals).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472718&req=5

f1-ijms-13-10880: Laser confocal images of Candida cells. Cells with membrane damage are seen stained with PI (red signals).
Mentions: Candida cells were grown and then stained with propidium iodide (PI) as described in materials and methods. PI penetrates only those cells which have severe membrane lesions; the entire yeast cell appears red. The laser confocal images of stained Candida cells exposed to test compounds are shown in Figure 1.

Bottom Line: Propidium iodide rapidly penetrated a majority of yeast cells when they were treated with the synthesized compounds at concentrations just above MIC, implying that fungicidal activity resulted from extensive lesions of the plasma membrane.Target compounds also caused a considerable reduction in the amount of ergosterol.The results also showed that the presence and position of different substituents on the phenyl ring of the acylhydrazone pendant seem to play a role on the antifungal activity as well as in deciding the fungistatic and fungicidal nature of the compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21413, Saudi Arabia; E-Mail: sthabaiti@kau.edu.sa.

ABSTRACT
Azoles are generally fungistatic, and resistance to fluconazole is emerging in several fungal pathogens. In an attempt to find novel azole antifungal agents with improved activity, a series of tetrazole ring bearing acylhydrazone derivatives were synthesized and screened for their in vitro antifungal activity. The mechanism of their antifungal activity was assessed by studying their effect on the plasma membrane using flow cytometry and determination of the levels of ergosterol, a fungal-specific sterol. Propidium iodide rapidly penetrated a majority of yeast cells when they were treated with the synthesized compounds at concentrations just above MIC, implying that fungicidal activity resulted from extensive lesions of the plasma membrane. Target compounds also caused a considerable reduction in the amount of ergosterol. The results also showed that the presence and position of different substituents on the phenyl ring of the acylhydrazone pendant seem to play a role on the antifungal activity as well as in deciding the fungistatic and fungicidal nature of the compounds.

No MeSH data available.


Related in: MedlinePlus