Microwave-assisted synthesis and myorelaxant activity of 9-indolyl-1,8-acridinedione derivatives

• Twelve novel 9-(substituted indolyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione derivatives have been synthesized.
• The structures of the compounds were confirmed by spectral methods including X-ray studies and elemental analysis.
• The efficacy of compound 9 was higher than pinacidil.
• The compounds bearing methyl substituents on the acridine backbone and bromine atom on the indole ring were more active.

In this study a microwave-assisted method was applied for the synthesis of novel 9-(substituted indolyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione derivatives. The structures of the compounds were confirmed by spectral methods including X-ray studies and elemental analysis.The Emax and pD2 values of the compounds and pinacidil were determined on noradrenaline precontracted tissues of isolated strips of rabbit gastric fundus smooth muscle. The obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on the strips. The efficacy of compound 9 was higher than pinacidil.Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. Methyl substituents on the acridine backbone and bromine atom on the indole ring led to more active compounds.

Compound 9 (3,3,6,6-Tetramethyl-9-(5-bromo-1H-indol-3-yl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione) was found to be the most active compound as a myorelaxant agent. Docking studies were carried out to find how this compound interacts with the active site of potassium channel. Figure optionsDownload as PowerPoint slide