Ex Vivo and In Vivo Study of Some Isoquinoline Precursors

Abstract

This article concerns the synthesis and biological activities of some N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides as isoquinoline precursors and compounds with smooth muscle (SM) relaxant activity. Aim: find the biological activity of N-(1-(3,4-dimethoxyphenyl)propan-2-yl) amides and compare it with papaverine, an isoquinoline alkaloid that has been known as a brain and coronary vasodilator and SM relaxant. Materials and methods: In silico simulation with the PASS online program predicts SM relaxant activity for the compounds. The amides were tested on the isolated gastric SM preparations (SMPs) from rats to determine their effects on spontaneous contractile activity (CA) compared with papaverine. The in vivo effect on the learning and memory processes of rats was also assessed. Results: the data from the isometric measurements showed that one of the compounds caused ex vivo relaxation in circular SM tissues isolated from the stomach (corpus) of male Wistar rats. Conclusion: We found that the compound’s SM relaxation uses the papaverine pathway. It also has an improving effect on the cognitive functions of learning and memory processes in rats.

Novel Anthranilic Acid Hybrids—An Alternative Weapon against Inflammatory Diseases

“…Reaction with acyl chlorides worked well and efficiently furnished the desired diamides 4a-e in 78-82% yield (Table 1). Functional groups, including phenyl and benzyl substituents, were well tolerated because of the previously found activity [33]. Reaction with acyl chlorides worked well and efficiently furnished the desired diamides 4a-e in 78-82% yield (Table 1).…”

“…Reaction with acyl chlorides worked well and efficiently furnished the desired diamides 4a-e in 78-82% yield (Table 1). Functional groups, including phenyl and benzyl substituents, were well tolerated because of the previously found activity [33]. The resultant compounds were characterized by their melting point, IR, 1 H, 13 C-NMR, and HRESIMS spectra.…”

Synthesis, Molecular Docking, and Biological Evaluation of Novel Anthranilic Acid Hybrid and Its Diamides as Antispasmodics

“…Ex vivo testing is frequently used to confirm the potential biological effect of newly synthesized experimental compounds and approved pharmaceuticals [ 19 ]. Because smooth muscle (SM) contraction can still create active tension when separated from the body, we were drawn to include them in the study design we chose [ 20 , 21 ] as a platform for ex vivo contractility evaluation. A number of internal organs’ primary structural components include SM tissue.…”

“…Given the interest in the field of drug discovery, examining the biological activity of recently synthesized compounds is an important scientific topic. Various substances, including 1,2,3,4-tetrahydroisoquinolines [ 26 ], isoquinoline precursors [ 20 ], and eucalyptol [ 27 ], among others, have been the subject of our prior publications on the synthesis and SM activity.…”

“…Finding new therapeutic strategies, manipulating established pharmacological targets, or validating novel agents with a different mechanism of action remain the top priority. Based on the pharmacological activities of anthranilic acid derivatives and phenylethylamines, as well as our previous experiments with 2-phenylethylamines [ 20 , 21 , 28 ], we considered the synthesis of a new hybrid molecule of anthranilic acid with 2-(3-chlorophenyl)ethylamine and its amides as antispasmodics. Density functional theory (DFT) calculation containing geometry optimization, molecular electrostatic potential (MEP) map, and highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy level, as well as a quantum chemical descriptor, were conducted to determine electronic behavior, reactive region, and stability and chemical reactivity of the compounds.…”