Substituted phenothiazines: synthesis and in silico evaluation of D4 dopamine receptor inhibition

Abstract

In the present paper we describe synthesis and molecular docking simulation of substituted phenothiazines. Halonitrobenzenes on reaction with thiols give 2-amino-2′-nitrodiphenylsulphides which on formylation with 90% formic acid yield 2-formamido-2′-nitrodiphenyl sulfides. This compound undergoes Smiles rearrangement to provide phenothiazines. To evaluate the antipsychotic property of the synthesized phenothiazines derivatives (5a-d and 7), molecular docking simulation study were performed into the binding pocket of D4 dopamine receptor. These compounds have shown acceptable binding affinity with the binding pocket of the D4 dopamine receptor similar to known inhibitors. Whereas, compound 7 has displayed higher affinity for D4 dopamine receptor compared to D3 and D2 receptors. All compounds interacted with critical residues for the inhibition of D4 dopamine receptor and hence can be developed as potent antipsychotic drugs.

Design, synthesis and characterization of novel Ni(II) and Cu(II) complexes as antivirus drug candidates against SARS-CoV-2 and HIV virus

“…Molecular docking sheds light on designing drugs for the treatment of many diseases [66] . This technique allows us to study the binding of ligands to proteins having greater significance to screen virtual libraries of drug-like molecules [67] . For this consideration, we have purposefully docked all the synthesized compounds with the main protease (M Pro ) of protein (PDB ID: 7BZ5 ) of SARS-CoV-2 [44] .…”

Experimental and computational study of naphthalimide derivatives: Synthesis, optical, nonlinear optical and antiviral properties

“…Therefore, it is crucial to examine their antiviral activity against SARS-CoV-2, which is devastating communities globally. Recent docking studies have proven to be effective in discovering several therapeutic drug targets [18] . Therefore, docking studies for the synthesized naphthalimide derivatives were performed herein along these lines.…”

Synthesis and Structure of Novel Phenothiazine Derivatives, and Compound Prioritization via In Silico Target Search and Screening for Cytotoxic and Cholinesterase Modulatory Activities in Liver Cancer Cells and In Vivo in Zebrafish

“…Our in silico clustering of targets across phenothiazines suggests unique interactions of molecule 10 with dopamine receptor D2, D3, and D4, this also warrants further investigation. Although phenothiazines are well-known as dopamine receptor modulators, more studies are needed if they lead to enhanced associations between dopamine receptor and AChE activities. − …”

“…Although phenothiazines are well-known as dopamine receptor modulators, more studies are needed if they lead to enhanced associations between dopamine receptor and AChE activities. 75 − 77 …”