Design and Development of coumarin hybrids as non classical carbonic anhydrase inhibitors

Abstract

The work carried out in my research tenure has been compiled in the form of a thesis entitled newline Design and development of coumarin hybrids as non-classical carbonic anhydrase newlineinhibitors . The main aim of this work is to design, synthesize and carry out biological studies of coumarin hybrids as carbonic anhydrase inhibitors. newlineThis thesis work has been divided into four chapters. newlineChapter-I presents a general introduction about carbonic anhydrases followed by their newlineclassification and mechanisms of inhibition. This is followed by a brief introduction and newlinedescription about cancer, hypoxia and pH regulation. Thereafter, human carbonic anhydrases(hCAs) IX, XII and XIII are discussed in detail, along with their biological implications. Finally, the heterocyclic scaffolds synthesized for this thesis work have been discussed, along with newlineliterature review of their carbonic anhydrase inhibitory profiles. newlineChapter-II describes the design, synthesis and biological evaluation of coumarin-3-carboxamides and coumarin-pyrazole-4-thiazolidinone hybrids as selective and potent inhibitors of hCAs IX and XII. newlineThis chapter is divided into two sections: newlineSection-2.1 illustrates the design, synthesis and biological evaluation of coumarin-3-carboxamides as selective carbonic anhydrase IX and XII inhibitors. newlineSection-2.2 illustrates the synthesis and biological evaluation of some coumarin hybrids as selective carbonic anhydrase IX and XII inhibitors. newlineChapter-III describes the design, synthesis and biological evaluation of coumarin-linked 1,2,4-oxadiazoles as selective carbonic anhydrase IX and XII inhibitors. newlineChapter-IV describes the synthesis and biological evaluation of coumarin-linked 1,2,3 triazoles and coumarin-thiourea hybrids as potent inhibitors of hCAs IX and XIII. newlineSection-4.1 illustrates the synthesis and biological evaluation of coumarin-linked 1,2,3 triazoles as potent inhibitors of hCAs IX and XIII. newlineSection-4.2 illustrates the synthesis and biological evaluation of coumarin-thiourea hybrids as potent inhibitors of hCAs IX and XI