Multicomponent reactions – the door to chemosensitizers

Solutions to urgent challenges, for instance in health or the environment, require intelligent and imaginative use of chemistry. The development of new drugs and materials is closely related to our ability to synthesize complex and functional molecules. In this context, organic synthesis plays a key role, with features such as versatility, sustainability, and atom-, step-, redox-, and time-economy determining the synthetic accessibility of a particular new compound. Multicomponent reactions (MCRs) are used in synthetic chemistry to produce a variety of new molecules and are defined by the simultaneous reaction of three or more starting materials in a reaction vessel to form a product. They are crucial in modern organic synthesis because of their high degree of reaction economy and efficiency in bond formation. Additionally, they can provide a wide range of connectivity patterns that cannot be prepared otherwise. However, the access to MCRs is much more limited compared to standard bimolecular transformations. Therefore, the discovery of new MCRs and their application in medicine is a fundamental area of research. The use of MCRs has already been successfully applied in the synthesis of drugs, such as in the production of anticancer agents. Although desired molecules with remarkable anticancer activity have been generated, many cancer types are highly adaptable and can evade conventional therapy by emergence of resistance. To address this development of resistance and to improve the response of patients to chemotherapy, it is essential to design new drugs that are effective against resistant cancer cells and counteract a possible treatment failure. MCRs are also very important in this respect, as a large number of molecules with novel structures can be generated quickly. Moreover, it is possible to incorporate special substructures that provide the drug with new properties such as fluorescence. This contributes, for example, to a better understanding of the uptake and metabolism of the compounds in the body. The aim of this project is to develop new MCR-processes and to apply MCRs for the synthesis of new potential drugs, which are capable of reversing resistance mechanisms to common chemotherapies. In order to evaluate their efficacy, the synthesized molecules will be tested on various resistant cancer cells in the course of the project. The discovery of active compounds could be of major significance in the treatment of malignancies, since they are designed specifically to prevent the mutation of cancer cells and re-sensitize resistant cells to chemotherapy. As cancer is one of the most common causes of death today and poses enormous challenges to health care systems worldwide, this project can be of high significance. The gained knowledge might be essential for progress in chemistry and medicine, especially in the development of effective chemosensitizers.

Solutions to urgent challenges, for instance in the health or environmental sectors, require intelligent and imaginative use of chemistry. The development of new drugs and materials is closely related to our ability to synthesize complex molecules. In this context, organic synthesis plays a key role, with features such as versatility, sustainability, and atom-, step , redox-, and time-economy determining the synthetic accessibility of a particular new compound. Multicomponent reactions (MCRs) are used in synthetic chemistry to produce a variety of new molecules and are defined by the simultaneous reaction of three or more starting materials in a reaction vessel to form a product. They are crucial in modern organic synthesis because of their high reaction economy and efficiency in bond formation. Additionally, they can provide a wide range of connectivity patterns that cannot be prepared otherwise. However, the access to MCRs is much more limited compared to standard bimolecular transformations. Therefore, the discovery of new MCRs and their application in medicine is a fundamental area of research. It needs to be stated that multistep synthesis is a bottleneck in drug discovery that requires tremendous efforts and resources, in addition to slowing down the entire process. Advantageously, the use of MCRs has already been successfully applied in the synthesis of drugs, e.g., in the production of anticancer agents. Although molecules with remarkable anticancer activity have been developed, many cancers are highly adaptable and can evade conventional therapy by acquiring resistance. To address this emergence of resistance and improve the response of patients to chemotherapy, it is essential to design new drugs that are effective against resistant cancer cells and counteract a possible treatment failure. MCRs are also very important in this respect, as numerous molecules with novel structures can be rapidly generated. Moreover, it is possible to incorporate special substructures that provide the drug with new properties such as fluorescence. This contributes, for example, to a better understanding of the uptake and metabolism of the compounds in the body. The aim of this project was to develop new MCR-processes and to apply MCRs for the synthesis of new potential drugs, which are capable of reversing resistance mechanisms to common chemotherapies. To evaluate their chemosensitizing efficacy, the synthesized molecules were tested on various resistant cancer cells in the course of the project. We discovered highly active compounds and assumed a novel mode of action that might be of major significance in the treatment of malignancies. As cancer is one of the most common causes of death today and poses enormous challenges to health care systems worldwide, this project can be of great importance. The knowledge gained might be essential for progress in chemistry and medicine, especially in the development of effective chemosensitizers.