Strategies for the synthesis of indole diketopiperazine alkaloids (indole DKPs) have been described and involve three analogs of indole DKPs. The antimicrobial activity and structure-activity relationship (SAR) of 24 indole DKPs were explored. Compounds 3b and 3c were found to be the most active, with minimum inhibitory concentrations (MIC) values in the range of 0.94–3.87 μM (0.39–1.56 μg/mL) against the four tested bacteria (Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli). Furthermore, compounds 4a and 4b displayed broad-spectrum antimicrobial activity with MIC values of 1.10–36.9 μM (0.39–12.5 μg/mL) against all tested bacteria and plant pathogenic fungi (Colletotrichum gloeosporioides, Valsa mali, Alternaria alternata and Alternaria brassicae). According to the in silico study, compounds 3c showed significant binding affinity to the FabH protein from Escherichia coli, which has been identified as the key target enzyme of fatty acid synthesis (FAS) in bacteria. Therefore, these compounds are not only promising new antibacterial agents but also potential FabH inhibitors.

A D-π-A type quinoline derivative, 2-(((4-(1, 2, 2-triphenylvinyl)phenyl)imino)methyl)quinolin-8-ol (HL), was synthesized and structurally characterized. The five-membered ring formed by the O-H···N hydrogen bond in HL contributed to the excited-state intramolecular proton transfer (ESIPT) behavior of HL, which was further verified by theoretical computations. Upon coordination with Zn²⁺, the hydroxyl proton in HL was removed, resulting in the inhibition of ESIPT. In the meanwhile, the formed Zn ₂ L ₄ complex displayed aggregation-induced emission (AIE) character in THF/H₂O mixtures, which is conducive to the fluorescence enhancement in aqueous media. Structure analysis suggested that the origin of the AIE characteristic was attributed to restriction of intramolecular rotations along with the formation of J-aggregates. Based on ESIPT coupled with AIE, HL could recognize Zn(II) in aqueous media via an orange fluorescence turn-on mode. Benefitting from the AIE property, chemosensor HL was successfully applied to fabricate test strips for rapid sensing of Zn(II) ions.

Triple-negative breast cancer (TNBC) lacks major effective target molecules and chemotherapy remains the current main treatment. However, traditional chemotherapy drugs, such as doxorubicin (DOX), cause serious side effects and have a poor prognosis. Piperlongumine (PL), a natural alkaloid, has showed selective anticancer effects and is expected to become a new strategy against TNBC. In our research, cell viability, colony formation, flow cytometry, Western blot, and tumor xenograft model assays were established to evaluate the suppression effect of PL and DOX alone and in combination. Data showed that PL could effectively inhibit cell growth and induce apoptosis in two TNBC cell lines. We also demonstrated for the first time that the combination treatment of PL and DOX synergistically inhibited cell growth and induced apoptosis in TNBC cells. The suppression of STAT3 activation was indicated to be a mechanism of the anticancer effect. Moreover, the effectiveness of this combination was confirmed in a tumor xenograft model. These results revealed that inhibition of the JAK2-STAT3 pathway was a key anticancer mechanism when treated with PL alone or combined with DOX, suggesting that the combination of PL and chemotherapy drugs may be a potential strategy for the clinical treatment of TNBC.

A new isoquinolone alkaloid named 5-hydroxy-8-methoxy-4-phenylisoquinolin-1(2H)-one (3), together with two known quinolinone alkaloids 3-O-methylviridicatin (1) and viridicatol (2) were isolated from the fermentation of an endophytic fungus Penicillium sp. R22 in Nerium indicum. Their structures were elucidated by NMR, IR and MS data, and were also confirmed by comparing with the reported data in the literature. Meanwhile, the antibacterial and antifungal activities of all compounds were tested, and the results showed that three compounds had strong antifungal activity. Among them, compound 2 revealed potent antibacterial activity against Staphylococcus aureus with MIC value of 15.6 μg/mL.