(1) Background: This investigation aimed at developing a series of c-Met-targeting cabozantinib-based PROTACs. (2) Methods: Purification of intermediate and target compounds was performed using column chromatography, in vitro antiproliferation activity was measured using a standard MTT assay and a c-Met degradation assay was performed via the immunoblotting technique. (3) Results: Several compounds exhibited antiproliferative activity towards different cell lines of breast cancer (T47D, MDA-MB-231, SKBR3, HCC1954 and MCF7) at the same level as parent cabozantinib and 7-demethyl cabozantinib. Two target conjugates, bearing a VHL-ligand as an E3-ligase binding moiety and glycol-based linkers, exhibited the effective inhibition of c-Met phosphorylation and an ability to decrease the level of c-Met in HCC1954 cells at micromolar concentrations. (4) Conclusions: Two compounds exhibit c-Met inhibition activity in the nanomolar range and can be considered as PROTAC molecules due to their ability to decrease the total level of c-Met in HCC1954 cells. The structures of the offered compounds can be used as starting points for further evaluation of cabozantinib-based PROTACs.
A series of theoretical and experimental studies was carried out with the aim of a direct comparison of the thermal and microwave destruction of peat during pyrolysis. Different heating mechanisms in these processes were investigated in the framework of simulations conducted using a commercial 3D software package, CST Studio Suite, to define their specific features. Based on these simulations, identical reactors were constructed exploiting an electric element and a microwave complex as a heat source, and an experimental technique was developed that allows these processes to be correctly compared under similar conditions. Using these reactors based on different heat sources, comparative experiments on peat pyrolysis were performed, and the results of the theoretical analysis were confirmed. As a result, the advantages of microwave exposure were demonstrated to achieve a more uniform and deep fragmentation of peat, increase the reaction rate and reduce the processing time, with high energy efficiency accompanying this method. As part of the experiments, the yield of pyrolysis products was analyzed. During the microwave destruction of peat, a high gas output (up to 27%) was obtained, which allows for a further increase in the efficiency of this processing method when burning these gases. The conducted elemental analysis showed an increase in the percentage of carbon from about 50% to 78% after microwave processing, which can become a raw material for obtaining effective environmentally friendly sorbents. The prospects for creating industrial microwave complexes for processing organic materials are discussed.