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Purpose: Antimicrobial resistance and virulence genes play important roles in increasing the severity of Pseudomonas aeruginosa infections, especially in hospitalized patients with high antibiotic pressure. Most genes that encode Pseudomonas aeruginosa virulence factors are controlled and regulated by the quorum sensing (QS) system. The aim of this study was to investigate the frequency of some virulence genes (rhlR, rhlI, lasR, lasI, lasB, toxA, aprA, algD, ExoS, and plcH genes) and their association with antibiotic resistance. Methods: Antimicrobial susceptibility was determined by Kirby-Bauer agar disk diffusion method. A total of 125 clinical isolates of P. aeruginosa were tested for some virulence genes using polymerase chain reaction (PCR). Results: The highest resistance was observed against cefepime (92.8%). Multi-drug resistant (MDR) P. aeruginosa represented 63.2% of total isolates with high distribution among wound isolates (21/79, 26.3% of MDR isolates). LasB was the most prevalent virulence gene among the tested isolates (89.6%) followed by aprA (85.6%), exoS (84%), algD (80%), toxA (76.8%), and plcH (75.2). Furthermore, a significant association (P < 0.05) among most of the tested virulence genes and MDR isolates was found. The presence of more than 5 virulence genes was highly observed among wound infections, otitis media, and respiratory tract infection isolates. Conclusion: The complex association of virulence genes including QS system regulating genes with antibiotic resistance indicates the importance of the tested factors in the progression of infections, which is considered a great challenge for the health-care team with the need for specific studies for each area having different antibiotic resistance profiles and the development of effective treatment strategies such as anti-virulent and quorum sensing inhibiting drugs against P. aeruginosa infections.
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BACKGROUND: Thiazoles, thiazolidinones and azetidinones are highly ranked amongst natural and synthetic heterocyclic derivatives due to their great pharmaceutical potential. RESULTS: New thiazolidinone and azetidinone class of bioactive agents based on 4-(2,7-dichloro-9H-fluoren-4-yl)thiazole moiety have been successfully synthesized. 4-(2,7-dichloro-9H-fluoren-4-yl)thiazol-2-amine was synthesized and allowed to react with various aryl/heteroaryl aldehydes to afford the corresponding Schiff base intermediates. The target thiazolidinone and azetidinone analogues have derived from Schiff bases by their reactions with thioglycolic acid and chloroacetyl chloride, respectively. The newly synthesized compounds were then evaluated for their antimicrobial activity against some multidrug resistant strains and examined for cytotoxic activity against normal lung fibroblast (WI-38), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231) cell lines to develop a novel class of fluorene-based bioactive agents. The mode of action and the binding interaction of the synthesized compound with the active sites of dihydrofolate reductase enzyme were well identified by fluorescence-activated cell sorting (FACS) analysis and molecular docking study. CONCLUSION: Some of the synthesized compounds showed remarkable activity against A-549 and MDA-MB-231 when compared to Taxol, which was used as a reference drug. 2,7-dichloro-9H-fluorene-based azetidinones are more efficient as antimicrobial and anticancer agents compared to dichloro-9H-fluorene-based thiazolidinones derivatives.
RESUMO
In this study, a new series of 2,7-dichloro-4-(2-substituted-amino acetyl)fluorene derivatives were synthesized, characterized and evaluated for their antimicrobial activity and screened for cytotoxic activity against human lung carcinoma (A-549) and human breast carcinoma (MCF-7) cell lines. Most of the synthesized compounds displayed significant activity against A-549 and MCF-7 cell lines when compared to 5-fluorouracil (5-FU), which was used as a reference drug. In addition, some of these reported novel compounds exhibited promising antibacterial and antifungal properties. A molecular docking study was performed to identify the mechanism of action of the synthesized compounds, which suggested binding interactions with the active sites of dihydrofolate reductase (DHFR).