Design, Synthesis, and Evaluation of New Sulfone Derivatives Containing a 1,3,4-Oxadiazole Moiety as Active Antibacterial Agents

This study aimed to synthesize some new sulfone derivatives containing a 1,3,4-oxadiazole moiety and investigate their in vitro antibacterial activities against <i>Xanthomonas oryzae</i> pv. <i>oryzae</i> (<i>Xoo</i>) and <i>Xanthomonas axonopodis</i> pv. <i>citri</i> (<i>Xac</i>), the pathogens of rice bacterial leaf blight and citrus canker, respectively, by performing turbidimeter tests. Antibacterial bioassay results showed that compound <b>6d</b> revealed excellent bioactivities against <i>Xoo</i> and <i>Xac</i>, with the 50% effective concentration (EC₅₀) values of 0.17 and 1.98 μg/mL, respectively, compared with thiodiazole copper (121.82 and 77.04 μg/mL, respectively) and bismerthiazol (92.61 and 58.21 μg/mL, respectively). Meanwhile, greenhouse-condition trials indicated that, compared with thiodiazole copper and bismerthiazol, compound <b>6d</b> more effectively reduced rice bacterial leaf blight

Table_1_Molecular typing and characterization of Staphylococcus aureus isolates from burn wound infections in Fujian, China.docx

BackgroundStaphylococcus aureus (S. aureus) is the most common causative agent of burn wound infection, that often leads to high morbidity and mortality. However, there is not enough knowledge about the molecular epidemiology and antimicrobial susceptibility of S. aureus isolates from burn wound infections in Fujian, China.MethodsBetween 2016 and 2021, 90 S. aureus isolates were collected from burn wound infections in Fujian, China, including 59 methicillin-resistant (MRSA) strains and 31 methicillin-susceptible (MSSA) strains. These were investigated for molecular characteristics, virulence genes, biofilms, and antimicrobial susceptibility. All the isolates were genotyped by multilocus sequence typing (MLST), spa typing, agr typing, and SCCmec typing. Conventional PCR was performed for the detection of virulence genes. Biofilm formation capacity was assessed by tissue culture plate assay (TCP). The antimicrobial susceptibility of the isolates was evaluated using the dilution method.ResultsIn total, 37 sequence types (ST) and 34 Staphylococcal protein A (spa) types (including a new type named spa-t20720) were identified based on multilocus sequence typing (MLST) and spa typing, respectively. CC8-ST239-t030-agrI-SCCmecIII (57.6%,34/59) and CC7-ST7-t091-agrI (16.1%, 5/31) represented the main clone of MRSA and MSSA isolates, respectively. Antibiotic susceptibility testing identified a significant difference in resistance rates between ST239 and non-ST239 isolates (p ConclusionCC8-ST239-t030-agrI-SCCmecIII and CC7-ST-7-t091-agrI were the prevalent molecular signatures of MRSA and MSSA isolates from burn wound infections in Fujian, China, respectively. The newly identified spa-t20720 isolate, which carries a wide range of virulence genes and has strong biofilm formation ability, requires special clinical attention.</p

Synthesis and antiviral activity of novel <i>a</i>-aminophosphonates containing 6-fluorobenzothiazole moiety

<p></p> <p>A series of novel a-aminophosphonates containing 6-fluorobenzothiazole moiety derivatives were synthesized by one-pot reaction under microwave irradiation and their structures were characterized by IR, ¹H, ¹³C, and ³¹P NMR and element analysis data. Antiviral assays showed that some compounds possess good curative and protective activities against tobacco mosaic virus (TMV) <i>in vivo</i> at 500 µg/mL In particular, compounds diethyl [(6-fluorobenzo[d]thiazol-2-ylamino)(phenyl)methyl]phosphonate (<b>4b</b>), diethyl [(6-methoxybenzo[d]thiazol-2-ylamino)(thiophen-2-yl)methyl]phosphonate (<b>4j</b>) and diphenyl [(6-fluorobenzo[d]thiazol-2-ylamino)(4-methoxyphenyl)methyl]phosphonate (<b>4q</b>) exhibited remarkable antiviral activities than Ribavirin against TMV and PVY. Compound diphenyl [(6-fluorobenzo[d]thiazol-2-ylamino)(4-methoxyphenyl)methyl]phosphonate (<b>4q</b>) showed similar curative and protective activity against potato virus Y (PVY) to Dufulin.</p

Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin

<p>Hydroxychloroquine (HCQ) inhibits autophagy and therefore can sensitize some cancer cells to chemotherapy, but the high doses required limit its clinical use. Here we show that loading HCQ into liposomes (HCQ/Lip) decorated with a pH-sensitive TH-RGD targeting peptide (HCQ/Lip-TR) can concentrate HCQ in B16F10 tumor cells and lysosomes. HCQ/Lip-TR was efficiently internalized as a result of its ability to bind ITGAV-ITGB3/integrin α_vβ₃ receptors highly expressed on the tumor cell surface and to undergo charge reversal from anionic at pH 7.4 to cationic at pH 6.5. Studies in vitro at pH 6.5 showed that the intracellular HCQ concentration was 35.68-fold higher, and lysosomal HCQ concentration 32.22-fold higher, after treating cultures with HCQ/Lip-TR than after treating them with free HCQ. The corresponding enhancements observed in mice bearing B16F10 tumors were 15.16-fold within tumor cells and 14.10-fold within lysosomes. HCQ/Lip-TR was associated with milder anemia and milder myosuppressive reductions in white blood cell and platelet counts than free HCQ, as well as less accumulation in the small intestine, which may reduce risk of intestinal side effects. In addition, co-delivering HCQ/Lip-TR with either free doxorubicin (DOX) or liposomal DOX improved the ability of DOX to inhibit tumor growth. Biochemical, electron microscopy and immunofluorescence experiments confirmed that HCQ/Lip-TR blocked autophagic flux in tumor cells. Our results suggest that loading HCQ into Lip-TR liposomes may increase the effective concentration of the inhibitor in tumor cells, allowing less toxic doses to be used.</p