The Effects of Novel Triazolopyrimidine Derivatives on H2S Production in Lung and Vascular Tonus in Aorta

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dc.authoridistanbullu, huseyin/0000-0002-0102-4181
dc.authoridKızrak, Ümran/0000-0003-1202-9903
dc.authorscopusid58576169800
dc.authorscopusid55315482800
dc.authorscopusid58620227600
dc.authorscopusid58237862500
dc.authorscopusid8970943500
dc.authorscopusid14032536900
dc.authorwosidistanbullu, huseyin/W-2458-2017
dc.authorwosidKızrak, Ümran/AAA-1538-2021
dc.contributor.authorÖzbek, Emine Nur
dc.contributor.authorİstanbullu, Huseyin
dc.contributor.authorKızrak, Umran
dc.contributor.authorAlan Albayrak, Elif
dc.contributor.authorSevin, Gülnur
dc.contributor.authorYetik-Anacak, Günay
dc.date.accessioned2024-08-25T18:32:00Z
dc.date.available2024-08-25T18:32:00Z
dc.date.issued2023
dc.departmentEge Üniversitesien_US
dc.description.abstractIntroduction: Hydrogen sulfide (H2S), known as a third gasotransmitter, is a signaling molecule that plays a regulatory role in physiological and pathophysiological processes. Decreased H2S levels were reported in inflammatory respiratory diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. H2S donors or drugs that increase H2S have emerged as novel treatments for inflammatory respiratory diseases. We previously showed that resveratrol (RVT) causes vascular relaxation and antioxidant effects by inducing H2S production. In the current study, we synthesized a new molecule Cpd2, as an RVT analog. We examined the effect of Cpd2 and its precursor chalcone compound (Cpd1) on H2S formation under both healthy and oxidative stress conditions in the lung, as well as vascular relaxation in the aorta. Methods: Cpd2 synthesized from Cpd1 with microwaved in basic conditions. H2S formation was measured by H2S biosensor in the mice lungs under both healthy and pyrogallol-induced oxidative stress conditions in the presence/absence of H2S synthesis inhibitor aminooxyacetic acid (AOAA). The effect of compounds on vascular tonus is investigated in mice aorta by DMT myograph. Results: RVT and Cpd2 significantly increased l-cysteine (l-cys) induced-H2S formation in the lung homogenates of healthy mice, but Cpd1 did not. Superoxide anion generator pyrogallol caused a decrease in H2S levels in mice lungs and Cpd2 restored it. Inhibition of Cpd2-induced H2S formation by AOAA confirmed that Cpd2 increases endogenous H2S formation in both healthy and oxidative stress conditions. Furthermore, we found that both Cpd1 and Cpd2 (10(-8)-10(-4) M) caused vascular relaxation in mice aorta. Discussion and Conclusion: We found that Cpd2, a newly synthesized RVT analog, is an H2S-inducing molecule and vasorelaxant similar to RVT. Since H2S has antioxidant and anti-inflammatory effects, Cpd2 has a potential for the treatment of respiratory diseases where oxidative stress and decreased H2S levels are present.en_US
dc.description.sponsorshipEge University [BAP 21428]en_US
dc.description.sponsorshipThe authors would like to thank the financial support of the Ege University BAP 21428 project.en_US
dc.identifier.doi10.1159/000533419
dc.identifier.issn0031-7012
dc.identifier.issn1423-0313
dc.identifier.pmid37696255en_US
dc.identifier.scopus2-s2.0-85172357065en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1159/000533419
dc.identifier.urihttps://hdl.handle.net/11454/100096
dc.identifier.wosWOS:001067753800001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherKargeren_US
dc.relation.ispartofPharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240825_Gen_US
dc.subjectHydrogen sulfideen_US
dc.subjectOxidative stressen_US
dc.subjectRespiratory diseasesen_US
dc.subjectResveratrolen_US
dc.subjectVascular relaxationen_US
dc.subjectHydrogen-Sulfideen_US
dc.subjectResveratrol Analogsen_US
dc.subjectAntioxidanten_US
dc.subjectMechanismen_US
dc.subjectStressen_US
dc.titleThe Effects of Novel Triazolopyrimidine Derivatives on H2S Production in Lung and Vascular Tonus in Aortaen_US
dc.typeArticleen_US

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