Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/122572
Title: DESIGN OF DUAL-TARGET INHIBITORS OF DIHYDROFOLATE REDUCTASE AND THIOREDOXIN REDUCTASE AS ANTICANCER AGENTS
Authors: NG HUI LI
Keywords: dihydrofolate reductase, thioredoxin reductase, designed multiple ligands, dual-target, cancer, drug discovery
Issue Date: 17-Aug-2015
Citation: NG HUI LI (2015-08-17). DESIGN OF DUAL-TARGET INHIBITORS OF DIHYDROFOLATE REDUCTASE AND THIOREDOXIN REDUCTASE AS ANTICANCER AGENTS. ScholarBank@NUS Repository.
Abstract: THE DIHYDROFOLATE REDUCTASE (DHFR) AND THIOREDOXIN REDUCTASE (TRXR) ENZYMES ARE INVOLVED IN THE PROCESS OF CANCER CELL GROWTH AND SURVIVAL. INHIBITION OF THESE ENZYMES CAN THEREFORE RESULT IN ANTIPROLIFERATIVE ACTIVITY ON CANCER CELLS. THE 4,6-DIAMINO-1,2-DIHYDRO-1,3,5-TRIAZINE SCAFFOLD IS WELL-ESTABLISHED AS A USEFUL SCAFFOLD FOR DHFR INHIBITION, WHILE CHALCONES HAVE BEEN REPORTED TO BE INHIBITORS OF TRXR. USING THE MTT ASSAY, WE FOUND THAT SOME COMBINATIONS OF 4,6-DIAMINO-1,2-DIHYDRO-1,3,5-TRIAZINES AND CHALCONES AT A 1:1 MOLAR RATIO DEMONSTRATED SYNERGISTIC ANTIPROLIFERATIVE ACTIVITIES ON THE HCT116 AND MCF-7 CANCER CELL LINES. BASED ON THIS RESULT, WE SYNTHESIZED TWENTY NOVEL COMPOUNDS CONTAINING BOTH THE 4,6-DIAMINO-1,2-DIHYDRO-1,3,5-TRIAZINE SCAFFOLD AND THE CHALCONE MOIETY. MANY OF THE COMPOUNDS DEMONSTRATED GOOD ANTIPROLIFERATIVE ACTIVITY AGAINST MCF-7 AND HCT116. IN VITRO ENZYME ASSAYS SHOWED THAT THE COMPOUNDS INHIBITED RECOMBINANT HUMAN DHFR AND RAT LIVER TRXR. CELL-BASE
URI: http://scholarbank.nus.edu.sg/handle/10635/122572
Appears in Collections:Ph.D Theses (Open)

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