Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety.
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ABSTRACT:
SUBMITTER: Shang R
PROVIDER: S-EPMC3871055 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
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Project description:Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus were tested by the agar dilution method and Oxford cup assay. All the screened compounds displayed potent activity. Compound 6d was the most active antibacterial agent because of its lowest MIC value and largest inhibition zone. Docking experiments were performed to understand the possible mode of the interactions between the derivatives and 50S ribosomal subunit. Moreover, the absorption, distribution, metabolism, excretion and toxicity properties of the synthesized compounds were analyzed after prediction using the Advanced Chemistry Development/Percepta Platform available online.
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Project description:To explore more efficient and less toxic antibacterial and antifungal pesticides, we utilized 2,6-difluorobenzamide as a starting material and ultimately synthesized 23 novel benzoylurea derivatives containing a pyrimidine moiety. Their structures were characterized and confirmed by 1H NMR, 13C NMR, 19F NMR, and HRMS. The bioassay results demonstrated that some of the title compounds exhibited moderate to good in vitro antifungal activities against Botrytis cinerea in cucumber, Botrytis cinerea in tobacco, Botrytis cinerea in blueberry, Phomopsis sp., and Rhizoctonia solani. Notably, compounds 4j and 4l displayed EC50 values of 6.72 and 5.21 μg/mL against Rhizoctonia solani, respectively, which were comparable to that of hymexazol (6.11 μg/mL). Meanwhile, at 200 and 100 concentrations, the target compounds 4a-4w exhibited lower in vitro antibacterial activities against Xanthomonas oryzae pv. oryzicola and Xanthomonas citri subsp. citri, respectively, compared to those of thiodiazole copper. Furthermore, the molecular docking simulation demonstrated that compound 4l formed hydrogen bonds with SER-17 and SER-39 of succinate dehydrogenase (SDH), providing a possible explanation for the mechanism of action between the target compounds and SDH. This study represents the first report on the antifungal and antibacterial activities of novel benzoylurea derivatives containing a pyrimidine moiety.
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