DerivativesAPN-A(Jinan University)

Apigeninidin (APN) is a flavonoid belonging to the 3-deoxyanthocyanidin family, exhibiting diverse biological activities and representing a potential natural antitumor compound. However, the poor lipophilicity and cell membrane permeability of APN limit its bioavailability and antitumor activity. To overcome these limitations, we designed a site-specific propynylation strategy and synthesized two derivatives, APN-A and APN-B, investigating how targeted modification alters APN's antitumor activity. Comparative analysis of the physicochemical properties and bioactivities of these compounds revealed that APN-A exhibited significantly enhanced cell membrane permeability and increased anticancer activity against cervical cancer cells compared to the parent compound APN. In vitro experiments further demonstrated that APN-A can dramatically reduce the viability of cervical cancer cells, inhibited cell proliferation and migration, and synergistically potentiate the antitumor efficacy of 5-fluorouracil (5-FU). In addition, chemical proteomics enrichment analyses indicated that APN-A shows its antitumor effects primarily by targeting and inhibiting processes such as DNA replication and protein transcription-translation in cancer cells via targeting proteins such as PARP-1, EIF3J, and TCEA1. These findings provide a methodological reference and mechanistic insight for the propynyl modification of APN, and highlight its potential applications in the food industry and drug development.