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The Anti-Multidrug-Resistant Acinetobacter baumannii Study on 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline Compounds.
In: Molecules, Jg. 27 (2022-12-01), Heft 23, S. 8609-8618
Online
academicJournal
Zugriff:
As a major public health problem, the prevalence of Acinetobacter baumannii (A. baumannii) infections in hospitals due to the pathogen's multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting Escherichia coli dihydrofolate reductase (ecDHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent A. baumannii DHFR (abDHFR)-inhibitors as well, which inspired us to consider their anti-A. baumannii abilities. We further found that three PQZ compounds, OYYF-171, -172, and -175, showed significant antibacterial activities against A. baumannii, including multidrug-resistant (MDR) strains, which are significantly stronger than the typical DHFR-inhibitor, trimethoprim (TMP), and superior to, or comparable to, the other tested antibacterial agents belonging to β-lactam, aminoglycoside, and quinolone. The significant synergistic effect between the representative compound OYYF-171 and the dihydropteroate synthase (DHPS)-inhibitor sulfamethoxazole (SMZ) was observed in both the microdilution-checkerboard assay and time-killing assay, which indicated that using SMZ in combination with PQZ compounds could help to reduce the required dosage and forestall resistance. Our study shows that PQZ is a promising scaffold for the further development of folate-metabolism inhibitors against MDR A. baumannii. [ABSTRACT FROM AUTHOR]
Titel: |
The Anti-Multidrug-Resistant Acinetobacter baumannii Study on 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline Compounds.
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Autor/in / Beteiligte Person: | Wu, Han ; Chen, Hongtong ; Zhang, Jungan ; Hu, Xinxin ; Xie, Chunyang ; Cao, Weiting ; Zhao, Ziqi ; Xiao, Zengshuo ; Ren, Yixin ; Dong, Luyao ; Sun, Peiyi ; You, Xuefu ; Yang, Xinyi ; Hong, Wei ; Wang, Hao |
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Zeitschrift: | Molecules, Jg. 27 (2022-12-01), Heft 23, S. 8609-8618 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 1420-3049 (print) |
DOI: | 10.3390/molecules27238609 |
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