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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.


Synthesis of 5-(4-chlorophenyl)-1H-tetrazole (A3).
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f4-ijms-13-10880: Synthesis of 5-(4-chlorophenyl)-1H-tetrazole (A3).

Mentions: Present study was undertaken to synthesize some novel tetrazole ring bearing acyl-hydrazone derivatives to investigate their probable antifungal effects. Target compounds were obtained in a five step reaction procedure as outlined in Schemes 1 and 2. First of all, 5-(4-chlorophenyl)-1H-tetrazole was synthesized from 4-chlorobenzonitrile by following a reported procedure [23]. 4-chlorobenzonitrile in turn was obtained from 4-chlorobenzaldehyde, via an oxime intermediate, following a standard protocol [24]. In the fourth step 2-[5-(4-chlorophenyl)-1H-tetrazol-1-yl] acetohydrazide (A5) was prepared from 5-(4-chlorophenyl)-1H-tetrazole (A3) following a reported reaction procedure [25]. The acyl-hydrazone derivatives (TH1–TH10) were obtained through a condensation reaction of 2-[5-(4-chlorophenyl)-1H-tetrazol-1-yl]-acetohydrazide (A5) with different aromatic aldehydes in ethanol medium in 1:1 molar ratio. The structure of formed acyl hydrazones was established by elemental analyses, FT-IR, 1NMR, 13CNMR and ESI-MS spectra.


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)

Synthesis of 5-(4-chlorophenyl)-1H-tetrazole (A3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-ijms-13-10880: Synthesis of 5-(4-chlorophenyl)-1H-tetrazole (A3).
Mentions: Present study was undertaken to synthesize some novel tetrazole ring bearing acyl-hydrazone derivatives to investigate their probable antifungal effects. Target compounds were obtained in a five step reaction procedure as outlined in Schemes 1 and 2. First of all, 5-(4-chlorophenyl)-1H-tetrazole was synthesized from 4-chlorobenzonitrile by following a reported procedure [23]. 4-chlorobenzonitrile in turn was obtained from 4-chlorobenzaldehyde, via an oxime intermediate, following a standard protocol [24]. In the fourth step 2-[5-(4-chlorophenyl)-1H-tetrazol-1-yl] acetohydrazide (A5) was prepared from 5-(4-chlorophenyl)-1H-tetrazole (A3) following a reported reaction procedure [25]. The acyl-hydrazone derivatives (TH1–TH10) were obtained through a condensation reaction of 2-[5-(4-chlorophenyl)-1H-tetrazol-1-yl]-acetohydrazide (A5) with different aromatic aldehydes in ethanol medium in 1:1 molar ratio. The structure of formed acyl hydrazones was established by elemental analyses, FT-IR, 1NMR, 13CNMR and ESI-MS spectra.

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.