Synthesis of Quinoline, Idane-1,3-Dione, Urea and Thiourea Derivatives and their Bioactivities

Abstract

This research work consists of the synthesis of quinoline, indane 1,3 dione and urea and thiourea derivatives by adopting various synthetic chemical transformations and screening of their biological activities. All compounds were fully characterized by various spectroscopic techniques such as 1H-NMR, 13C-NMR, EI-MS/FAB-MS and HRMS. Melting points of all compounds were also recorded. This dissertation consists of three chapters based on the extensive literature and research findings regarding the five libraries of synthetic compounds. Each chapter has its own compounds numbering, tables, figures, schemes and references Chapter-1 composed of the broad literature survey regarding the general introduction of quinoline, its biological background and various synthetic protocols. This chapter is divided into three parts. Synthesis of Quinoline derivatives and their structure-activity relationship studies 30-52 (Part A), benzamide derivatives of quinoline 53-83(Part B), Sulfonamide and Sulfonyl ester deravatives of quinoline 84-133(Part C) and evaluation of their in vitro activities. Compounds 31, 32, 35, 42, 43 and 48 showed good to moderate antiglycation activity. Compound 34 showed moderate leishmanicidal activity. Compound 41 was found to be more potent than standard thiourea. All compounds are non toxic on rat fibroblast 3T3 cell lines. Compounds 30, 41, 42, and 47 were showed good antiinflammatory potential and found to be more potent than standard ibuprofen. Compounds 53-83 were found to be inactive against immunomodulatory, leshminasis, DPPH and dipeptidyl peptidase activity. Compound 84-133 were screened for βGlucuronidase activity. Out of which Compounds 85-91, 93, 95, 97, 98,101-105, 110, 112 and 115 were found to be more potent than standard D-Saccharic acid 1,4 lactone. Their random screening resulted in finding of some lead molecule for further studies. Chapter-2 demonstrated the Synthesis of urea and thiourea analogs and their biological studies 134-175. Compounds 140, 142, 143, 162, 163, 167 and 170 were more potent than standard thiourea.While compounds 141, 144, 145, 150, 164, 166, 172 and 173 were found to be moderate active in urease inhibitory activity. Chapter 3 Comprises the synthesis of Indane 1,3 dione derivatives and their structure activity relationship studies. Biological screening of all compounds showed that compounds 174, 182, 185, 188-191, 194-197 and 199 showed moderate to weakly leishmanicidal activity. Compound 201 was moderately active in antioxidant assay.