Inhibition of P53/miR-34a improves diabetic endothelial dysfunction via activation of SIRT1 was written by Wu, Junduo;Liang, Wenzhao;Tian, Yueli;Ma, Fuzhe;Huang, Wenlin;Jia, Ye;Jiang, Ziping;Wu, Hao. And the article was included in Journal of Cellular and Molecular Medicine in 2019.Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide The following contents are mentioned in the article:
Endothelial dysfunction contributes to diabetic macrovascular complications, resulting in high mortality. Recent findings demonstrate a pathogenic role of P53 in endothelial dysfunction, encouraging the investigation of the effect of P53 inhibition on diabetic endothelial dysfunction. Thus, high glucose (HG)-treated endothelial cells (ECs) were subjected to pifithrin-α (PFT-α)-a specific inhibitor of P53, or P53-small interfering RNA (siRNA), both of which attenuated the HG-induced endothelial inflammation and oxidative stress. Moreover, inhibition of P53 by PFT-α or P53-siRNA prohibited P53 acetylation, decreased microRNA-34a (miR-34a) level, leading to a dramatic increase in sirtuin 1 (SIRT1) protein level. Interestingly, the miR-34a inhibitor (miR-34a-I) and PFT-α increased SIRT1 protein level and alleviated the HG-induced endothelial inflammation and oxidative stress to a similar extent; however, these effects of PFT-α were completely abrogated by the miR-34a mimic. In addition, SIRT1 inhibition by EX-527 or Sirt1-siRNA completely abolished miR-34a-I’s protection against HG-induced endothelial inflammation and oxidative stress. Furthermore, in the aortas of streptozotocin-induced diabetic mice, both PFT-α and miR-34a-I rescued the inflammation, oxidative stress and endothelial dysfunction caused by hyperglycemia. Hence, the present study has uncovered a P53/miR-34a/SIRT1 pathway that leads to endothelial dysfunction, suggesting that P53/miR-34a inhibition could be a viable strategy in the management of diabetic macrovascular diseases. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide).
2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at δ 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica