Design Synthesis and Biological Evaluation of Acridone based Derivatives as Anti Cancer Agents

Abstract

At present chemotherapy is the best approach used for the treatment of cancer. However, the toxicity of available drugs and the development of resistance over existing drugs increases the need for the development of newer anti-cancer agents with low toxicity and high efficacy. Hence, many scientists are struggling to develop newer chemotherapeutic molecules. In this direction, the nitrogen-containing heterocycles have always shown promising anti-cancer activity and are in clinical use. Acridone is one of the interesting scaffolds, constituting a group of analogs with a wide range of biological activity with multiple mechanisms. The recent research on acridone has opened new directions for the design and development of AKT inhibitors as potent anti-cancer agents. Hence, targeting AKT provides an attractive approach for the development of promising molecules with good anti-cancer activity and low toxicity. In this research, a series of compounds bearing acridone-2-carbohydrazides, N-substituted acridone-2-carboxamide, and acridone-N-acetamide derivatives were designed based on the availability of earlier reported molecules. A total of 65 compounds were synthesized with efficient yields and characterized by analytical techniques (LCMS, IR, HPLC, and NMR). All the compounds were screened against various human cancer cell lines including A-549 (lung), A-431 (skin), MCF-7, and MDA-MB-231 (breast), etc. All these compounds were tested against normal mouse embryonic fibroblast (NIH/3T3) cells to determine their toxicity against normal cells. Then potential molecules were identified and used further to discover their underlying molecular mechanism. newlineIn vitro cytotoxicity evaluation revealed that most of the compounds showed significant cytotoxicity against all of them except A-431. The in vitro cytotoxicity assay identified 12 active compounds (A11, A20, A22, A31, AF-9, AN-8, AN-9, PA-4, PA-6, PB-4, PB-5, and PB-6) which displayed potent anti-proliferative activity, especially in MCF-7 cells. newline