Truncated N6-substituted-4′-oxo- and 4′-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A2A and A3 adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA2AAR, but hydrophobic C8 substitution abolished binding at the hA2AAR. However, most of synthesized compounds displayed medium to high binding affinity at the hA3AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA2AAR agonists. C2 substitution probed geometrically through hA2AAR-docking, was important for binding in order of hexynyl > hexenyl > hexanyl. Compound 4g was the most potent ligand acting dually as hA2AAR agonist and hA3AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases.
Approximately 20% of couples worldwide are infertile and about half of these couples have male infertility. Therefore, it is important to develop effective strategies for preventing male infertility. In this study, we examined the effects and regulatory mechanisms of curcumin, an active ingredient in the traditional herbal treatment derived from the dietary spice turmeric (Curcuma longa), on exogenous scrotal heat stress-induced testicular injuries in mice. Adult mice were orally administered three different doses of curcumin (20, 40, or 80 mg per kg per day) for 14 consecutive days and then subjected to transient scrotal heat stress at 43 °C for 20 min on day 7. The testes and blood of the mice were collected on day 14. Mice exposed to heat stress showed low testicular weight, severe vacuolization of seminiferous tubules followed by loss of spermatogenic cells, and the appearance of multinucleated giant cells and degenerative Leydig cells. In addition, great changes in oxidative stress (lipid peroxidation, superoxide dismutase (SOD) activity, cytoplasmic SOD, mitochondrial SOD, and phospholipid hydroperoxide glutathione peroxidase mRNAs), apoptosis (B-cell lymphoma-extra large and caspase 3 mRNAs), heat shock reaction (heat shock transcription factor-1 and transforming growth factor-β1 mRNAs) and androgen biosynthesis (testosterone concentration and 3β-hydroxysteroid dehydrogenase mRNA) were observed. However, all these testicular injuries induced by the scrotal hyperthermia were significantly improved by curcumin treatment (20, 40 and 80 mg kg(-1)) in a dose-dependent manner via its antioxidative, anti-apoptotic and androgen synthesis effects, indicating that it has the potential to prevent male infertility.
Purpose – The purpose of this study is to investigate whether complaint behavior intentions and expectations of service recovery based on the justice theory are different among customers from collectivistic versus individualistic cultures. A secondary purpose is to find which service recovery strategies are appropriate for different culture-based complaint behavior intentions. Design/methodology/approach – A survey was conducted at universities, and the survey population consisted of college students, who are known to be frequent users of fast-food restaurants. A total of 304 usable questionnaires were collected. Confirmatory factor analysis was conducted to verify the validity of the items, Cronbach’s alpha coefficients were used to examine the internal consistency of the factors, and an independent sample t-test was used to analyze differences in complaint behavior intentions and expectations of service recovery efforts in terms of cultural difference. Findings – The results of this study indicated that South Koreans revealed more voice complaint behavior intentions than Americans did. However, there were no significant differences in expectations of service recovery efforts between them. Second, American customers who indicated voice and private complaint behavior intentions expected distributive, procedural and interpersonal justice in complaint-handling procedures. South Korean customers who indicated voice complaint behavior intentions expected distributive and procedural justice, and South Korean customers who indicated private complaint behavior intentions anticipated interactional justice in complaint-handling procedures. Research limitations/implications – Understanding customers’ complaint behavior intentions and expectations of service recovery based on the justice theory and cultural differences will suggest practical implications to hospitality industry managers for effective service quality management. Originality/value – Understanding customers’ complaint behavior intentions and expectations of service recovery based on the justice theory and cultural differences will suggest practical implications to hospitality industry managers for effective service quality management.
The truncated C2- and C8-substituted-4′-thioadenosine derivatives 4a-d were synthesized from D-mannose, using palladium-catalyzed cross coupling reactions as key steps. In this study, an A3 adenosine receptor (AR) antagonist, truncated 4′-thioadenosine derivative 3 was successfully converted into a potent A2AAR agonist 4a (Ki = 7.19 ± 0.6 nM) by appending a 2-hexynyl group at the C2-position of a derivative of 3 that was N6-substituted. However, C8-substitution greatly reduced binding affinity at the human A2AAR. All synthesized compounds 4a-d maintained their affinity at the human A3AR, but 4a was found to be a competitive A3AR antagonist/A2AAR agonist in cyclic AMP assays. This study indicates that the truncated C2-substituted-4′-thioadenosine derivatives 4a and 4b can serve as a novel template for the development of new A2AAR ligands.
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