ABSTRACT
A series of novel hybrid molecules between sulfonamides and active antimicrobial 14-o-(3-carboxy-phenylsulfide)-mutilin were synthesized, and their in vitro antibacterial activities were evaluated by the broth microdilution. Results indicated that these compounds displayed potent antimicrobial activities in vitro against various drug-susceptible and drug-resistant Gram-positive bacteria such as Staphylococci and streptococci, including methicillin-resistant Staphylococcus aureus, and mycoplasma. In particular, sulfapyridine analog (6c) exhibited more potent inhibitory activity against Gram-positive bacteria and mycoplasma, including Staphylococcus aureus (MIC = 0.016-0.063 µg/mL), methicillin-resistant Staphylococcus aureus (MIC = 0.016 µg/mL), Streptococcus pneumoniae (MIC = 0.032-0.063 µg/mL), Mycoplasma gallisepticum (MIC = 0.004 µg/mL), with respect to other synthesized compounds and reference drugs sulfonamide (MIC = 8-128 µg/mL) and valnemulin (MIC = 0.004-0.5 µg/mL). Furthermore, comparison between MIC values of pleuromutilin-sulfonamide hybrids 6a-f with pleuromutilin parent compound 3 revealed that these modifications at 14 position side chain of the pleuromutilin with benzene sulfonamide could greatly improve the antibacterial activity especially against Gram-positives.
Subject(s)
Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/pharmacology , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology , Anti-Infective Agents/chemistry , Diterpenes/chemical synthesis , Diterpenes/chemistry , Diterpenes/pharmacology , Drug Design , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests/methods , Mycobacterium/drug effects , Polycyclic Compounds , Staphylococcus aureus/drug effects , Streptococcus/drug effects , Sulfonamides/chemistry , PleuromutilinsABSTRACT
In this study, a specific and sensitive LC-MS/MS method for the simultaneous analysis of type-B trichothecenes (deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol) and the de-epoxy metabolite of deoxynivalenol (de-epoxy-deoxynivalenol) in chicken muscle, liver, kidney, and fat tissues was developed and validated. The method involved an extraction step using ethyl acetate, followed by the evaporation of the supernatant, which was further purified by an Oasis HLB SPE cartridge (Waters, Milford, MA, USA). Chromatographic separation was performed on a C18 column by detection with MS in multiple-reaction monitoring mode and using a gradient elution program with 0.1% formic acid in water and methanol. The correlation coefficients (r) for each calibration curve were >0.99 within the experimental concentration range. The extraction recoveries ranged from 73.7 to 106.4%, with intraday and interday RSD < 11.6% at three levels of concentrations of 2, 10, and 100 µg/kg. The decision limits and the detection capabilities of the analytes in the chicken tissues ranged from 0.16 to 0.92 and 0.68 to 2.07 µg/kg, respectively. The results demonstrated the applicability of this sensitive procedure to the determination of trichothecenes in chicken tissue samples.
