Therapeutic Potential of 1-(2-Chlorophenyl)-6,7-dimethoxy-3-methyl-3,4-dihydroisoquinoline.
Valeri SlavchevVera N GledachevaMina PenchevaMiglena MilushevaStoyanka NikolovaIliyana StefanovaPublished in: Molecules (Basel, Switzerland) (2024)
The synthesized compound 1-(2-chlorophenyl) 6-7-dimethoxy-3-methyl-3,4-dihydroisoquinoline (DIQ) was investigated as a biological agent. Its potential to affect muscle contractility was predicted through in silico PASS analysis. Based on the in silico analysis, its capabilities were experimentally investigated. The study aimed to investigate the effects of DIQ on the ex vivo spontaneous contractile activity (CA) of smooth muscle (SM) tissue. DIQ was observed to reduce the strength of Ca 2+ -dependent contractions in SM preparations (SMP), possibly by increasing cytosolic Ca 2+ levels through the activation of a voltage-gated L-type Ca 2+ channel. DIQ potently affected calcium currents by modulating the function of muscarinic acetylcholine receptors (mAChRs) and 5-hydroxytryptamine (5-HT) receptors at a concentration of 50 μM. Immunohistochemical tests showed a 47% reduction in 5-HT 2A and 5-HT 2B receptor activity in SM cells and neurons in the myenteric plexus (MP), further confirming the effects of DIQ. Furthermore, a significant inhibition of neuronal activity was observed when the compound was co-administered with 5-HT to SM tissues. The conducted experiments confirm the ability of the isoquinoline analog to act as a physiologically active molecule to control muscle contractility and related physiological processes.
Keyphrases
- smooth muscle
- skeletal muscle
- induced apoptosis
- protein kinase
- molecular docking
- gene expression
- signaling pathway
- spinal cord
- cell cycle arrest
- mass spectrometry
- cell proliferation
- brain injury
- spinal cord injury
- oxidative stress
- ultrasound guided
- molecular dynamics simulations
- single molecule
- subarachnoid hemorrhage
- blood brain barrier