کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1392717 | 1501150 | 2013 | 11 صفحه PDF | دانلود رایگان |
• 1, 3, 4-thiadiazoles synthetized as conformationally restricted capsaicin analogues.
• The compounds were evaluated on rat and chicken TRPV1 receptor.
• 1, 3, 4-thiadiazoles showed to act as potent antagonist of TRPV1 receptor.
4-hydroxy-3-methoxybenzaldehyde was used as starting material to obtain a number of 1, 3, 4-thiadiazole alkylamide derivatives. The pharmacological properties of these conformationally restricted capsaicin analogues were evaluated on HEK-293T cells transiently expressing TRPV1 receptor. By means of a highthroughput calcium imaging assay we find that 1, 3, 4-thiadiazoles (compounds 8–15) act as potent antagonists of the capsaicin receptor, inhibiting both, the capsaicin- and temperature-dependent activation. Docking studies suggested a different binding orientation on the vanilloid binding site when compared with capsaicin analogues, such as 5-iodononivamide. Overall, our studies suggest that 1, 3, 4-thiadiazoles interact with capsaicin's binding region of the receptor, although using a different set of interactions within the vanilloid binding pocket.
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Journal: European Journal of Medicinal Chemistry - Volume 66, August 2013, Pages 193–203