ATP citrate lyase (ACLY) is an important metabolic enzyme involved in the synthesis of fatty acid and cholesterol. The inhibition of ACLY is considered as a promising therapeutic strategy for various metabolic diseases and numerous malignancies. In this study, a novel macrocyclic compound 2 has been identified as a potent ACLY inhibitor with the "ring closing" strategy for conformational restriction based on NDI-091143. It showed potent ACLY inhibitory activity and binding affinity comparable to the positive control. Furthermore, compared with the positive control (T 1/2 = 3.36 min), the metabolic stability of 2 in HLMs (T 1/2 = 531.22 min) was significantly improved. All of these results characterized 2 as a promising lead compound worthy of further study

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Photodynamic sterilization technology (PDT) is widely used in disease therapy, but its application in the food industry is still at the research stage because of the limitations of food-grade photosensitizers. Curcumin exhibits photosensitivity and is widely used as a food additive for its natural color. This study aimed to determine the effect of curcumin-mediated photodynamic technology (Cur-PDT) on Bacillus subtilis and to elucidate the anti-bacterial mechanism involved. First, the effects of curcumin concentration, duration of light irradiation, light intensity, and incubation time on the inactivation of B. subtilis were analyzed. It was found that Cur-PDT inactivated 100% planktonic cells with 50 μmol/L curcumin in 15 min (120 W). Then, the cell morphology, oxidation state and the expression of membrane structure- and DNA damage-related genes of B. subtilis vegetative cells were investigated under different treatment conditions. The membrane permeability of cells was enhanced and the cell membrane structure was damaged upon treatment with Cur-PDT, which were exacerbated with increases of treatment time and curcumin concentration. Meanwhile, the production of reactive oxygen species increased and the activities of the antioxidant enzymes SOD, GPX, and CAT decreased inside the cells. Furthermore, the Cur-PDT treatment significantly downregulated the mRNA of the membrane protein TasA and upregulated the DNA damage recognition protein UvrA and repair protein RecA of B. subtilis. These results suggested that curcumin-mediated PDT could effectively inactivate B. subtilis by inducing cell redox state imbalance, damaging DNA, and disrupting membrane structures.