| Synthesis and Molecular Modeling of New Indole-3-(CO)-benzothiazolamide Derivatives as Renin Inhibitors |
| کد مقاله : 1164-ICOC |
| نویسندگان |
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غلامعباس چهاردولی *1، محبوبه اسفندیاری2، احمد عبادی2، محمد رضا مهدیان2 1دانشگاه علوم پزشکی، دانشکده داروسازی 2دانشگاه علوم پزشکی همدان |
| چکیده مقاله |
| The renin-angiotensin system (RAS) is a key regulator of blood pressure. Inhibiting renin, the system's rate-limiting enzyme, represents a highly efficient therapeutic strategy for hypertension and organ protection [1,2]. In this study, we first synthesized 3-indoleglyoxylyl chloride (1) from the reaction of indole with oxalyl chloride. This intermediate was then used to synthesize a series of indole-3-(CO)-benzothiazolamides (2a-e) via its reaction with various 1-aminobenzothiazole derivatives (Scheme 1). Docking studies revealed that the indole-3-(CO)-benzothiazolamide derivatives form a key hydrogen bond with Asp32 and interact with Asp215 via van der Waals interactions in the active site of renin. Although the nitro-substituted derivative exhibited the most favorable (maximum negative) free energy of binding, the unsubstituted derivative was computationally predicted to be the most efficient inhibitor. |
| کلیدواژه ها |
| Indole-3-(CO)-benzothiazolamide, Indole-3-carboxamides, Renin inhibitors, blood pressure, Molecular docking |
| وضعیت: پذیرفته شده |