(2-Arylhydrazonomethyl)-substituted xanthones as antimycotics: synthesis and fungistatic activity against Candida species (original) (raw)
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Antifungal and Antibacterial Activity of the Newly Synthesized 2-Xanthone Derivatives
Archiv der Pharmazie, 2009
A series of 2-substituted xanthone derivatives 8 -20 containing selected allyl, cinnamyl, morpholine, and imidazole moieties were synthesized and tested for their antifungal and antibacterial in-vitro properties. Of the newly synthesized derivatives, ten revealed antifungal activity especially against Trichophyton mentagrophytes (the biggest inhibition zones ranged 35 mm for 11 and 13). 2-(3-(Allylamino)propoxy)-9H-xanthen-9-one hydrochloride 9 inhibited growth of all of the examined fungal species. Significant efficacy against evaluated yeasts and dermatophytes was also observed for 6-chloro-2-methyl-9H-xanthen-9-one derivatives 11 -13 containing encyclic amine moieties. Additionally, compounds 9, 11, and 12 hindered development of bacteria species but in a lesser degree. They were efficacious against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis.
2012
Background: The currently available antifungal drugs suffer from toxicity, greatest potential drug interactions with other drugs, insufficient pharmacokinetics properties, and development of resistance. Thus, development of new antifungal agents with optimum pharmacokinetics and less toxicity is urgent task. In the search for new azole antifungals, we have been previously described azolylchromanone oxime ethers as rigid analogs of oxiconazole. In continuation of our work, we incorporated phenylhydrazone moiety instead of oxime ether fragment in azolylchromanone derivatives. Methods: The 3-azolyl-4-chromanone phenylhydrazones were synthesized via ring closure of 2-azolyl-2'-hydroxyacetophenones and subsequent reaction with phenylhydrazine. The biological activity of title compounds was evaluated against different pathogenic fungi including Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum. Docking study, in silico toxicity risks and drug-likeness predictions were used to better define of title compounds as antifungal agents. Results: The in vitro antifungal activity of compounds based on MIC values revealed that all compounds showed good antifungal activity against C. albicans, S. cerevisiae and M. gypseum at concentrations less than 16 μg/mL. Among the test compounds, 2-methyl-3-imidazolyl derivative 3b showed the highest values of drug-likeness and drug-score.
In the present work, series of dihydrazone derivatives of adamantly moiety has been prepared by condensation of dihydrazide with different aldehydes and ketones to give the corresponding dihydrazone derivatives. The structure of newly synthesized compound is confirmed by FTIR, 1HNMR and elemental analysis. The new synthesized compounds were tested for the activities against fungusCandida albicans. The results revealed that the compounds display potential antifungal activity against Candida albicans.
A series of 21 1,3,4-oxadiazoline derivatives was synthesized by cyclization of N-acylhydrazones with acetic anhydride and evaluated for their in vitro antifungal activity against six Candida strains: Candida albicans (ATCC 90028 and LM V-42), C. krusei (ATCC 6258 and LM 12 C) and C. tropicalis (ATCC 13803 and LM 14). The Candida strains were found to be sensitive to some of the compounds, which inhibited the growth by 50-90%, with minimum inhibitory concentration (MIC) in the range of 64-512 μg mL-1. The compounds’ structures were fully confirmed and characterized by Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonance (NMR) and mass spectrometry (MS).
Journal of Molecular Structure, 2019
A new series of glycosylated acylhydrazones was synthesized and all the chemical structures were confirmed by High Resolution Mass Spectrometry (HRMS), 1 H and 13 C Nuclear Magnetic Resonance (1 H-NMR; 13 C-NMR) and Fourier Transform Infrared (FTIR) spectroscopy methods. The mass accuracy between the calculated and found values observed in HRMS analyses were near or lower than 5 ppm, which are acceptable for proposing a molecular formula using this technique. All of the synthesized compounds were screened for their antibacterial, antifungal and antiviral activity. Five compounds (12, 13, 14, 16 and 19) exerted a modest antifungal activity against the strains evaluated. Derivative 14 showed fungicidal activity against Candida glabrata at 173.8 µM and saccharide unit contributed to the increase of the antifungal potential against this strain. New chemical manipulation of derivative 14 can make it possible to obtain new potentially antimicrobial agents.
2-Acylhydrazino-5-arylpyrrole derivatives: synthesis and antifungal activity evaluation
European journal of medicinal chemistry, 2009
The synthesis and antifungal activity of 2-acylhydrazino-5-arylpyrroles 21-62 are described. Pyrrole derivatives 21-62 were evaluated for their antifungal activity towards Candida albicans ATCC 10231 and three Candida non-albicans isolated from clinical specimens. Most of them showed very good antifungal activities against Candidae, having MIC values in the 0.39-3.12 mg/mL range and enhanced inhibition potency as compared to that of fluconazole. In addition, some of the most active compounds were tested for cytotoxic activities against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines with the NCI anticancer drug screen. The activity of pyrroles described in this paper, along with the low toxicity, shows promise for the future development of non-toxic new antimycotic agents. The relationship between functional group variation and biological activity of the evaluated compounds is also discussed. required 3-(2-acylhydrazino)-3-aminopropenoates 4-14 and 3-(2acylhydrazino)-3-aminopropenenitriles 15-20 were prepared by treatment of imidates 1-3 with acylhydrazines using the method described in our previous papers . Intermediates 4-20 were converted to pyrroles 21-62 ) by treatment with the appropriate a-bromoketone in 1:1 molar ratio, in the presence of sodium hydrogencarbonate, in anhydrous MeCN solution. All the newly synthesized compounds gave corrected analytical data. The IR and NMR spectral data were consistent with the assigned structure.
Journal of Medicinal Chemistry, 2002
The synthesis, anti-Candida activity, and quantitative structure-activity relationship (QSAR) studies of a series of 2,4-dichlorobenzylimidazole derivatives having a phenylpyrrole moiety (related to the antibiotic pyrrolnitrin) in the R-position are reported. A number of substituents on the phenyl ring, ranging from hydrophobic (tert-butyl, phenyl, or 1-pyrrolyl moiety) to basic (NH 2 ), polar (CF 3 , CN, SCH 3 , NO 2 ), or hydrogen bond donors and acceptor (OH) groups, were chosen to better understand the interaction of these compounds with cytochrome P450 14-Rlanosterol demethylase (P450 14DM ). Finally, the triazole counterpart of one of the imidazole compounds was synthesized and tested to investigate influence of the heterocyclic ring on biological activity. The in vitro antifungal activities of the newly synthesized azoles 10p-v,x-c′ were tested against Candida albicans and Candida spp. at pH 7.2 and pH 5.6. A CoMFA model, previously derived for a series of antifungal agents belonging to chemically diverse families related to bifonazole, was applied to the new products. Because the results produced by this approach were not encouraging, Catalyst software was chosen to perform a new 3D-QSAR study. Catalyst was preferred this time because of the possibility of considering each compound as a collection of energetically reasonable conformations and of considering alternative stereoisomers. The pharmacophore model developed by Catalyst, named HYPO1, showed good performances in predicting the biological activity data, although it did not exhibit an unequivocal preference for one enantiomeric series of inhibitors relative to the other. One aromatic nitrogen with a lone pair in the ring plane (mapped by all of the considered compounds) and three aromatic ring features were recognized to have pharmacophoric relevance, whereas neither hydrogen bond acceptor nor hydrophobic features were found. These findings confirmed that the key interaction of azole antifungals with the demethylase enzyme is the coordination bond to the iron ion of the porphyrin system, while interactions with amino acids localized in proximity of heme could modulate the biological activity of diverse antifungal agents. In conclusion, HYPO1 conveys important information in an intuitive manner and can provide predictive capability for evaluating new compounds.
Bioorganic & Medicinal Chemistry Letters, 2014
Eighteen N-(4-aryl/cyclohexyl)-2-(pyridine-4-yl carbonyl) hydrazinecarbothioamide derivatives were synthesized, evaluated against ten clinical isolates of Candida spp. and compared with itraconazole. Introduction of p-chloro (2c), p-iodo (2q), m-chloro (2l) and o-nitro (2r) substitution at phenyl ring of thiosemicarbazide enhanced the anti-Candida activity. Compound (2c) bearing p-cholorophenyl ring was found to be the most effective against Candida albicans ATCC 66027, Candida spp. 12810 (blood) and Candida spp.
Archiv der Pharmazie, 1993
The synthesis and antifungal activities of aryl-lH-pyrrol-2-yI-lH-imidazol-I-yl-methanes having allyl, crotyl, and acrylate chains linked to the N-pyrrole atom and substituted at phenyl ring by CI, F, CH3, and NOz groups are reported. In vifro tests against Candida alhicans and Candida spp. showed 2,4-dichlorophenyl-1 -allyI-IH-pyrrol-2-yl-Wimidazol-1 -ylmethane to be the most potent derivative with activities comparable to those of ketoconazole and slightly inferior to those of bifonazole and miconazole. Some structure-activity relationships are discussed.