Evodiamine (Evo) is a quinazolinocarboline alkaloid found in Evodia rutaecarpa and exhibits moderate antiproliferative activity. Herein, we report using a scaffold-hopping approach to identify a series of novel polycyclic heterocyclic derivatives based on Evo as the topoisomerase I (Top1) inhibitor for the treatment of triple-negative breast cancer (TNBC), which is an aggressive subtype of breast cancer with limited treatment options. The most potent compound 7f inhibited cell growth in a human breast carcinoma cell line (MDA-MB-231) with an IC50 value of 0.36 μM. Further studies revealed that Top1 was the target of 7f, which directly induced irreversible Top1–DNA covalent complex formation or induced an oxidative DNA lesion through an indirect mechanism mediated by reactive oxygen species. More importantly, in vivo studies showed that 7f exhibited potent antitumor activity in a TNBC-patient-derived tumor xenograft model. These results suggest that compound 7f deserves further investigation as a promising candidate for the treatment of TNBC.

Pharmacological targeting cancer stem cells are emerging as a novel therapeutic modality for cancer treatment and prevention. Human cytochrome P450 enzyme CYP4Z1 represents a promising target for its potential role in attenuating the stemness of breast cancer cells. In order to develop potent and selective CYP4Z1 inhibitors, a series of novel N-hydroxyphenylformamidines were rationally designed and synthesized from a pan-CYP inhibitor HET0016. CYP4Z1 inhibitory activities of the newly synthesized derivatives were evaluated, and the structure–activity relationships (SARs) were summarized. Among them, compound 7c exhibited the best inhibitory activity with an IC50 value of 41.8 nM. Furthermore, it was found that 7c decreased the expression of stemness markers, spheroid formation, and metastatic ability as well as tumor-initiation capability in a concentration-dependent manner in vitro and in vivo. Altogether, compound 7c might be a potential lead compound to develop CYP4Z1 inhibitor with more favorable druggability for clinical application to treat breast cancer.

With the improvement of informatization and the wide application of artificial intelligence technology, the rapid development of Internet Finance and the development of technology have promoted the improvement of security and management of commercial banks. Based on the basic concepts of dynamic face recognition technology and quantum computing, combined with the technological development process and the application status of security prevention and control scenario, business handling scenario and personalized service scenario in bank personal business, this paper explores the feasibility of integrating quantum computing into the innovative practice of dynamic face recognition in view of the problems of dynamic face recognition. The paper mainly summarize the effectiveness of pattern innovation design and the problems that should be paid attention to the process setting. In conclusion, integrating quantum computing into dynamic facial recognition more effectively will be the direction for banks to explore personal business in the future.

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