1. The Effects of Novel Triazolopyrimidine Derivatives on H2S Production in Lung and Vascular Tonus in Aorta.
- Author
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Ozbek, Emine Nur, Istanbullu, Huseyin, Kızrak, Umran, Alan Albayrak, Elif, Sevin, Gülnur, and Yetik-Anacak, Gunay
- Subjects
RESVERATROL ,HYDROGEN sulfide ,AORTA ,CHRONIC obstructive pulmonary disease ,LUNGS ,OXIDATIVE stress ,PULMONARY hypertension - Abstract
Introduction: Hydrogen sulfide (H
2 S), known as a third gasotransmitter, is a signaling molecule that plays a regulatory role in physiological and pathophysiological processes. Decreased H2 S levels were reported in inflammatory respiratory diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. H2 S donors or drugs that increase H2 S have emerged as novel treatments for inflammatory respiratory diseases. We previously showed that resveratrol (RVT) causes vascular relaxation and antioxidant effects by inducing H2 S 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 H2 S 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. H2 S formation was measured by H2 S biosensor in the mice lungs under both healthy and pyrogallol-induced oxidative stress conditions in the presence/absence of H2 S 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-H2 S formation in the lung homogenates of healthy mice, but Cpd1 did not. Superoxide anion generator pyrogallol caused a decrease in H2 S levels in mice lungs and Cpd2 restored it. Inhibition of Cpd2-induced H2 S formation by AOAA confirmed that Cpd2 increases endogenous H2 S 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 H2 S-inducing molecule and vasorelaxant similar to RVT. Since H2 S has antioxidant and anti-inflammatory effects, Cpd2 has a potential for the treatment of respiratory diseases where oxidative stress and decreased H2 S levels are present. [ABSTRACT FROM AUTHOR]- Published
- 2023
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