Photoredox-catalyzed reaction as a powerful tool for rapid natural product Gem -dimethylation modification: discovery of potent anti-cancer agents with improved druggability

Tylophorine has diverse biological activities; however, the stability, solubility, and central nervous system toxicity have severely limited use of tylophorine. The gem -dimethyl group is an organic chemistry functional group that consists of two methyl groups bonded to the same carbon atom. This feature has gained significant attention in medicinal chemistry due to its unique properties and potential applications in drug design. We applied a new photoredox methodology to tylophorine modification, resulting in a series of gem-dimethyl tylophorine analogues. Among the analogues, compound 4b demonstrated promising activity against a wide range of tumor cell lines and exhibited significantly improved drug-like properties, including enhanced solubility and stability. Compound 4b showed an exceptional inhibitory effect (7.8 nM) against a C481S mutation-induced ibrutinib-resistant non-Hodgkin’s lymphoma cell line, as well as primary tumor cell lines obtained from patients. Importantly, compound 4b exhibited significantly reduced anti-proliferative activity against the normal cell line tested, indicating the potential for an enhanced therapeutic window for compound 4b . Based on these early-stage data, we believe that our study provides a solid foundation for the development of new therapeutic agents for potential drug-resistant cancer treatment in the near future

Data - Driven Prediction of Corrosion Rate of 3C Steel in Marine Environment

For predicting the corrosion rate of 3C steel quickly and accurately,a support vector regression (RBF-SVR) model based on Gaussian kernel function and an ensemble model based on three models were developed using the data obtained from literatures.The RBF-SVR model was established after dimension reduction of the data set realized respectively through the SVR-based genetic algorithm,forward algorithm and backward algorithm,and after optimizing super-parameter using leave-one-out cross validation method and grid search.Finally,the obtained model and two other models from published literatures (GA-BPNN model and BPNN model with four layers) were integrated to form an ensemble model.The research results indicated that the ensemble model had higher prediction accuracy and generalization ability