ABSTRACT
To address the emergency caused by multi-drug resistant Staphylococcus aureus, a series of novel capsaicin derivatives with nitrothiophene substituents have been designed and evaluated for the antibacterial activities against S. aureus Newman and multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). The structure-activity relationship was further revealed. Compound 13c, 13f, and 13g were highly active against staphylococcal growth, with minimal inhibition concentration (MIC) values of 0.39-1.56 µg/mL. The oxadiazole-derived compound 21, a bioisostere of ester 13f, is the most potent candidate for anti-growth of five multidrug-resistant S. aureus strains with MICs of 0.20-0.78 µg/mL, which is more active compared with vancomycin in vitro. Notably, these anti-staphylococcal compounds are much less cytotoxic to the normal kidney epithelial cell line (HK293T).
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Capsaicin/chemical synthesis , Methicillin-Resistant Staphylococcus aureus/drug effects , Staphylococcal Infections/drug therapy , Thiophenes/chemistry , Anti-Bacterial Agents/pharmacology , Capsaicin/pharmacology , Cell Survival/drug effects , Drug Design , Drug Resistance, Multiple , HEK293 Cells , Humans , Microbial Sensitivity Tests , Oxadiazoles/chemistry , Structure-Activity Relationship , Vancomycin/pharmacologyABSTRACT
Previously we identified a series of amidoalkylindoles as potent and selective CB2 partial agonists. In the present study, we report our continuous effort to improve the aqueous solubility by introducing N atoms to the amidoalkylindole framework. Synthesis, characterization, and pharmacology evaluations were described. Bioisosteric replacements of the indole nucleus with an indazole, azaindole and benzimidazole were explored. Benzimidazole 43 (EC50,CB1 = NA, EC50,CB2 = 0.067 µM) and azaindole 24 (EC50,CB1 = NA, EC50,CB2 = 0.048 µM) were found to be potent and selective CB2 receptor partial agonists, both with improved aqueous solubility.
ABSTRACT
<p><b>OBJECTIVE</b>To study the kinetics of MG7 expression in the process of gastric cancer development.</p><p><b>METHODS</b>The expression level of antigen MG7 on gastric mucosa in 406 cases was determined by immunohistochemical techniques. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry techniques on gastric mucosa in 82 cases.</p><p><b>RESULTS</b>The positive rates of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer all increased gradually (P < 0.01). The positive rates of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer increased in sequence (P < 0.01). The positive rate of antigen MG7 expression in III intestinal metaplasia of gastric mucosa was significantly different with I and II intestinal metaplasia (P < 0.05).</p><p><b>CONCLUSIONS</b>MG7 was quite specific in gastric cancer thus could be used as a good index in the screening of gastric cancer. Patients with III intestinal metaplasia of gastric mucosa, atrophic gastritis and dysplasia of gastric mucosa should be closely followed in order to improve the early detection on gastric cancer. It seemed that MG7 was clinically valuable in the dynamic follow-up of gastric precursors.</p>
