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Efficient synthetic methods that avoid the extensive use of hazardous reagents and solvents, as well as harsh reaction conditions, have become paramount in the field of organic synthesis. Organocatalysis is notably one of the best tools in building chemical bonds between carbons and carbon-heteroatoms; however, most examples still employ toxic volatile organic solvents. Although a portfolio of greener solvents is now commercially available, only ethyl alcohol, ethyl acetate, 2-methyltetrahydrofuran, supercritical carbon dioxide, ethyl lactate, and diethyl carbonate have been explored with chiral organocatalysts. In this review, the application of these bio-based solvents in asymmetric organocatalytic methods reported in the last decade is discussed, highlighting the proposed mechanism pathway for the transformations.

Cancer resistance to chemotherapy and radiation therapies presents significant challenges, necessitating the exploration of alternative approaches. Targeting specific proteins at the molecular level, particularly their active sites, holds promise in addressing this issue. We investigated the potential of 4′-methoxy-2-nitrochalcone (MNC) as an MCL-1 inhibitor, examining its chemical and structural characteristics to elucidate its biological activity and guide the selection of potential candidates. We conducted a docking study, followed by synthesis, structural characterization, theoretical calculations, and in vitro experiments to comprehensively evaluate MNC. The docking results revealed MNC’s excellent binding within the active site of MCL-1. At 50 µM, MNC demonstrated 99% inhibition of HCT116 cell proliferation, with an IC50 value of 15.18 µM after 24 h. Treatment with MNC at 30.36 and 15.18 µM resulted in reduced cell density. Notably, MNC exhibited marked cytotoxicity at concentrations of 15.58 µM and 7.79 µM, inducing high frequencies of plasma membrane rupture and apoptosis, respectively. Our findings highlight the significant biological potential of MNC as an MCL-1 inhibitor. Furthermore, we propose exploring chalcones with hydrogen bond acceptor substituents as promising candidates for studying inhibitors targeting this protein. In conclusion, our study addresses the challenge of cancer resistance by investigating MNC as an MCL-1 inhibitor. Through detailed characterization and experimental validation, we establish the efficacof MNC in inhibiting cell proliferation and inducing cytotoxic effects. These results underscore the potential of MNC as a valuable therapeutic agent and suggest the use of chalcones with hydrogen bond acceptor substituents as a basis for developing novel MCL-1 inhibitors.

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