Y18

A series of pyrimidine-2,4-diamine analogues were designed and synthesized. Their anticancer activity and the underlying mechanism against colorectal cancer (CRC) HCT116 cells and non-small cell lung cancer (NSCLC) A549 cells were investigated. The results demonstrated that the active compound Y18 significantly inhibited cancer cell proliferation by inducing robust cell cycle arrest and cell senescence through the persistence of DNA damage. Additionally, Y18 exhibited significant inhibitory effects on the adhesion, migration and invasion of cancer cells in vitro. Mechanistically, Y18 achieved these anticancer activities by suppressing GTSE1 transcription and expression. Y18 also effectively inhibited tumor growth in vivo with minimal side effects. Furthermore, Y18 exhibited a suitable half-life and oral bioavailability (16.27%), with limited inhibitory activity on CYP isoforms. Taken together, these results suggested that Y18 could be a potential chemotherapeutic drug for cancer treatment, particularly in cases of GTSE1 overexpressed cancers.

In order to discover novel compounds with excellent agricultural activities, novel flavonol derivatives containing 1,3,4-thiadiazole were synthesized and evaluated for their antifungal activities. The bioassay results showed that some of the target compounds had good antifungal activities against Botrytis cinerea, Phomopsis sp. and Sclerotinia sclerotiorum in vitro. It is worth noting that the half-effective concentration (EC₅₀) value of Y18 against B. cinerea was 2.4 μg/mL, which was obviously superior to that of azoxystrobin (21.7 μg/mL). The curative activity of Y18 at 200 μg/mL (79.9%) was better than that of azoxystrobin (59.1%), and its protective activity (90.9%) was better than that of azoxystrobin (83.9%). Morphological studies by using scanning electron microscopy and fluorescence microscopy revealed that Y18 could affect the normal growth of B. cinerea mycelium. In addition, the mechanism of action studies indicated that Y18 could affect the integrity of cell membranes by inducing the production of endogenous reactive oxygen species and the release of the malondialdehyde content, leading to membrane lipid peroxidation and the release of cell contents. The inhibitory activity of flavonol derivatives containing 1,3,4-thiadiazole on plant fungi is notable, offering significant potential for the development of new antifungal agents.