Insilico Design and Synthesis of Azaphenothiazine Analogues as Antidepressant

Abstract

The research study reports the effective synthesis of sixteen new compounds of 1-Azaphenothiazine analogues. By using insilico methods the biological, bioavailability and toxicity of forty compounds designed and determined. Docking work was performed with Auto dock vina using two enzymes Acetyl cholinesterase and Human Mono amine oxidase A. Bioavailability studies were predetermined with Swiss Absorption, Distribution, Metabolism and Excretion (ADME) and Toxicity studies by toxicity assessement. Biologically active compounds with good bioavailability and less toxicity were selected and synthesized. The starting material 2-Amino thiophenol reacts with 2, 3, 5-trichloro pyridine in alkali medium to formed 3-Choro 1-Azaphenothiazine. On further treatment with in the presence of base using ligand undergoes Buchwald Hartwig Cross Coupling method resulted in 3, 7 di substituted 1-Azaphenothiazine derivatives. The structures of the synthesized compounds were confirmed by IR, 1H NMR, 13H NMR and Mass spectral analysis. The synthesized azaphenothiazine derivatives were screened for Invitro antioxidant activity by DPPH method. The compounds N (4-chlorophenyl)-10H-pyrido [3, 2-b] [1, 4] benzothiazin-3-amine, N (4-methoxyphenyl)-10H-pyrido [3, 2-b] [1, 4] benzothiazin-3-amine, N (2-methoxyphenyl)-10H-pyrido[3, 2-b] [1, 4] benzothiazin-3-amine exhibited significant activity and comparing with the standard ascorbic acid. Further research can be carried out in this moiety to convert laboratory chemical to a drug to hospital site. The compound N-(2-methoxyphenyl)-10H-pyrido [3, 2-b] [1, 4] benzothiazine-3-amine showed potent antidepressant activity in all the methods. It is necessary to carry out further studies in order to clarify the antidepressant mechanism and establish that the bioactive molecules are in nano-form in order to improve the bioavailability and effectiveness of the drug. The overall, the research finding exposes that, most of the synthesized compounds were active towards all the screened activities. newline