SYNTHESIS AND EVALUATION OF N-AND S HETEROCYCLES AS ANTI-PARKINSON AGENTS

Abstract

The thesis entitled ‘Synthesis and Evaluation of N- and S-Heterocycles as Anti-Parkinson Agents’ has been carried out to design and synthesize the MAO-B inhibitors for Parkinson’s Disease (PD). The work has been divided into four chapters excluding reference section. Chapter 1 covers the description of PD and possible pathways for treatments. The literature given in this chapter covers the role of MAO-B inhibitors for the treatment of PD. Chapter 2 is the experimental section which explains the procedures for the synthesis of different N- and S-containing heterocyclic molecules. The methods for the synthesis of pyrazole derivatives, thiazole derivatives, 2-(4-nitrophenyl)-1H-benzimidazole, 2-(4- aminophenyl)-1H-benzimidazole, pyrazole-thiazole conjugates through amide bond and amine bond and benzimidazole-pyrazole/thiazole conjugates through amide bond and amine bond have been given in this chapter. Method for in-silico studies, in-vitro studies, and anti-oxidant studies have also been covered in this chapter. Chapter 3 is the results and discussion chapter which covers detailed explanation about the design of molecules through their in-silico studies. The in-silico studies have been carried out for individual compounds and their conjugates. A total of 309 compounds have been docked, which included pyrazole-thiazole derivatives (amide linkage), benzimidazole pyrazole/thiazole derivatives (amide linkage), pyrazole-thiazole derivatives (amine linkage), and benzimidazole-pyrazole/thiazole derivatives (amine linkage). A novel, facile, one-pot, multicomponent protocol for the synthesis of 5-amino-1H-pyrazole-4-carbonitrile derivatives (4) has been developed using alumina–silica supported MnO2 as recyclable catalyst in water and sodium dodecyl benzene sulphonate at room temperature. A sustainable, one-pot, multicomponent protocol for the synthesis of 4-phenylthiazole-2-amine derivatives catalyzed by MoS2 QDs in aqueous medium has been developed. The cyclo-condensation of phenacyl bromide and thiourea gave the thiazole derivatives in 89–96% yields. Apart from this, their amide and amine conjugates have also been synthesized. The synthesized derivatives were evaluated for MAO-B inhibition. The in-vitro study of fifteen compounds was done using Amplex™ Red Monoamine Oxidase Assay Kit. The two compounds P11 and P10 with IC50 values of 80.17 and 86.03 μM have been identified as potential molecules. The antioxidant evaluation of the compounds has also been done. The results showed 13 to 83 % antioxidant activities of the compounds. Interestingly, the compounds that shows better in-vitro results also showed good antioxidant activities.