Synthesis, Characterization and Pharmacological Evaluation of Some 1,2,4-Triazole, 1,3,4-Oxadiazole, Triazolothiadiazole and Indolinone Derivatives

Abstract

The work presented in the thesis consists of the synthesis, characterization and pharmacological evaluation of nitrogen-containing heterocyclic compounds. For convenience, the research work presented in this thesis has been divided into four chapters. The first chapter includes, the synthesis, characterization and pharmacological evaluation of 4,5- disubstituted-1,2,4-triazole-3-thiones and 4,5-disubstituted-1,2,4-triazole-3-ones. Both of these target compounds were synthesized by four-step syntheses involving a series of reactions, including esterification of substituted aromatic acids, hydrazide formation and their condensation with substituted isothiocyanates and substituted isocyanates resulting in the formation of thiosemicarbazides and semicarbazides. The former were obtained by refluxing thiosemicarbazides in sodium hydroxide solution (4N) and the latter were formed by refluxing semicarbazides in sodium hydroxide solution (2N). The final products were obtained by neutralizing the reaction mixtures with dilute hydrochloric acid solution. Later on, the synthesized compounds were screened for their antifungal, anti-inflammatory, acetylcholinesterase, alkaline phosphatase and -glucoronidase activities. The second chapter includes the synthesis, characterization and pharmacological evaluation of 1,3,4-oxadiazoles. These compounds were synthesized by refluxing aromatic acid hydrazides with carbon disulfide in ethanolic potassium hydroxide. All of these compounds were checked for their cytotoxic activities using three different cell lines. The third chapter includes the synthesis, characterization and pharmacological evaluation of triazolothiadiazoles-substituted bridged heterocycles. The synthesis involves the formation of 5- substituted-4-amino-1,2,4-triazole-3-thiones by stirring different aromatic hydrazides with carbon disulfide in methanolic potassium hydroxide and resulted in the formation of potassium dithiocarbazinate salts, which on refluxing with hydrazine hydrate, yielded 5-substituted-4- amino-1,2,4-triazoles-3-thiones. Triazolothiadiazoles were formed by refluxing different aromatic acids with 5-substituted-4-amino-1,2,4-triazoles-3-thiones in phosphoryl chloride. All the synthesized compounds were screened for antibacterial, acetylcholinesterase and alkaline phosphatase activities. The fourth chapter addresses the synthesis, characterization and pharmacological evaluation of Schiff bases of isatin, which are known as indolinone derivatives. These compounds were synthesized by the reaction of acid hydrazides with substituted isatins in ethanol. The synthesized compounds were screened for cytotoxic activity.