Abstract
In an effort to develop new potent antimicrobial and anticancer agents, new pyrrole-based chalcones were designed and synthesized via the base-catalyzed Claisen-Schmidt condensation of 2-acetyl-1-methylpyrrole with 5-(aryl)furfural derivatives. The compounds were evaluated for their in vitro antimicrobial effects on pathogenic bacteria and Candida species using microdilution and ATP luminescence microbial cell viability assays. MTT assay was performed to determine the cytotoxic effects of the compounds on A549 human lung adenocarcinoma, HepG2 human hepatocellular carcinoma, C6 rat glioma, and NIH/3T3 mouse embryonic fibroblast cell lines. 1-(1-Methyl-1H-pyrrol-2-yl)-3-(5-(4-chlorophenyl)furan-2-yl)prop-2-en-1-one (7) and 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(2,5-dichlorophenyl)furan-2-yl)prop-2-en-1-one (9) were found to be the most potent antifungal agents against Candida krusei and therefore these compounds were chosen for flow cytometry analysis and Ames MPF assay. ATP bioluminescence assay indicated that the antifungal activity of compounds 7 and 9 against C. krusei was significantly higher than that of other compounds and the reference drug (ketoconazole), whereas flow cytometry analysis revealed that the percentage of dead cells treated with compound 7 was more than that treated with compound 9 and ketoconazole. According to Ames MPF assay, compounds 7 and 9 were found to be non-genotoxic against TA98 and TA100 with/without metabolic activation. MTT assay indicated that 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(2-nitrophenyl)furan-2-yl)prop-2-en-1-one (3) showed more selective anticancer activity than cisplatin against the HepG2 cell line. On the other hand, 1-(1-methyl-1H-pyrrol-2-yl)-3-(5-(4-nitrophenyl)furan-2-yl)prop-2-en-1-one (1) was found to be more effective and selective on the A549 cell line than cisplatin.
Highlights
Infections caused by pathogenic bacteria represent a major public health burden, not just in terms of morbidity and mortality, and in terms of increased healthcare costs [1]
In order to evaluate the flow cytometry results, we focused on C. krusei since the MIC results of compounds 7 and 9 on C. krusei were statistically significant in this series
The results indicated that the activity of the compounds is very close to ketoconazole and there were only ~2% differences (Table 2)
Summary
Infections caused by pathogenic bacteria represent a major public health burden, not just in terms of morbidity and mortality, and in terms of increased healthcare costs [1]. Opportunistic fungal infections, those caused by Candida spp., Molecules 2017, 22, 2112; doi:10.3390/molecules22122112 www.mdpi.com/journal/molecules have emerged as major causes of morbidity and mortality in immunocompromised patients. [3,4,5,6].On. Onthe theother otherhand, hand,cancer cancerhas hasbecome becomethe the leading cause death with minimal minimal host leading cause of of death in in developed countries [7]. The design of chemotherapy has become considerably developed countries [7]. The design of chemotherapy has become considerably sophisticated, no cancer cancer treatment treatment that that is is 100%
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