The crystal growth behavior of dendrite-like Cu₂O crystals during galvanostatic electrodeposition was investigated. The deposited Cu₂O particles are single-phase cuprites and their morphologies change from octahedral in a static electrolyte to dendrites in a stirred electrolyte. The morphology evolution is attributed to the enhancement of the transfer of Cu²⁺ and the break in the Cu²⁺ depletion zone around the nuclei, which promotes the deposition of Cu²⁺ ions along the directions to form a face-centered cubic (FCC) Cu lattice under a cathodic potential. Meanwhile, O atoms diffuse into the Cu lattice to form a cuprite Cu₂O lattice with a corresponding lattice expansion. Consequently, the morphology of the Cu₂O crystals develops into dendrites and the growth direction of the dendritic branches are all along the directions. Furthermore, the conduction type of Cu₂O was also changed from p-type to n-type when the morphology of the Cu₂O crystals varied from octahedral to dendrites. The mechanism of the morphology evolution in the present reaction system is helpful for controlling the morphology of the Cu₂O crystals.

Thieno[3,2-d]pyrimidine as an effective pharmacophore has been extensively studied. However, its 2,6-substituted derivatives are rarely reported. In the present study, eighteen 2,6-substituted thieno[3,2-d]pyrimidine derivatives containing electrophilic warheads were designed based on the first known Fibroblast growth factor receptor-4 (FGFR4) inhibitor Blu9931. Unexpectedly, all of the derivatives exhibited negligible activity against FGFR4. However, most of the target compounds exhibited antiproliferative activities against four human cancer cell lines, including A431, NCI-H1975, Ramos and SNU-16. Compound 12 showed the most potent antiproliferative activities on the above four cell lines with IC₅₀ values of 1.4 μM, 1.2 μM, 0.6 μM, and 2.6 μM, respectively. Additionally, the antiproliferative activity of 12 against MDA-MB-221 proved that 12 had the selectivity towards certain tumor cell lines. Furthermore, preliminary structure-activity relationship analysis was discussed based on the experimental data.

Nine new mycophenolic acid derivatives, penicacids O–W (1–9), two first-time reported natural products (10, 11), and five known compounds (12–16), were isolated from a marine-derived fungus Penicillium senticosum RCDB005 found in a South China Sea sediment sample. Their structures were determined using NMR, HRESIMS, and optical rotatory dispersion (ORD) spectra, electronic circular dichroism (ECD) calculations, X-ray crystallography, and modified Mosher’s methods. Eight of these compounds were evaluated for anti-proliferative effects against nine human cancer cell lines and the IC₅₀ values ranged from nM to μM levels. Compounds 5, 7–9 showed potent inhibition activity against MOLM-13 acute myeloid leukemia cells with IC₅₀ values between 0.13 and 1.13 μM.

Drawing inspiration from the structural resemblance between a natural product N-(3-carboxypropyl)-2-acetylpyrrole and phenylbutyric acid, a pioneer HDAC inhibitor evaluated in clinical trials, we embarked on the design and synthesis of a novel array of HDAC inhibitors containing an N-linked 2-acetylpyrrole cap by utilizing the pharmacophore fusion strategy. Among them, compound 20 exhibited potential inhibitory activity on HDAC1, and demonstrated notable potency against RPMI-8226 cells with an IC₅₀ value of 2.89 ± 0.43 μM, which was better than chidamide (IC₅₀ = 10.23 ± 1.02 μM). Western blot analysis and Annexin V-FTIC/propidium iodide (PI) staining showed that 20 could enhance the acetylation of histone H3, as well as remarkably induce apoptosis of RPMI-8226 cancer cells. The docking study highlighted the presence of a hydrogen bond between the carbonyl oxygen of the 2-acetylpyrrole cap group and Phe198 of the HDAC1 enzyme in 20, emphasizing the crucial role of introducing this natural product-inspired cap group. Molecular dynamics simulations showed that the docked complex had good conformational stability. The ADME parameters calculation showed that 20 possesses remarkable theoretical drug-likeness properties. Taken together, these results suggested that 20 is worthy of further exploration as a potential HDAC-targeted anticancer drug candidate.

Neuroendocrine prostate cancer (NEPC) is a highly aggressive cancer that is resistant to hormone therapy and characterized by poor prognosis, as well as limited therapeutic options. Since the natural product lycobetaine was reported to exhibit good antitumor activities against various types of cancers, we initially simplified the scaffold of lycobetaine to obtain the active compound 1, an isoquinoline derivative with an aryl moiety substitution at the 4-position, which showed apparent antiproliferative activities against NPEC cell line LASCPC-01 in vitro. Subsequently, we carried out structural optimization and systematic structure–activity relationship (SAR) studies on compound 1, leading to the discovery of compound 46, which demonstrated potent inhibitory activities against the LASCPC-01 cell line with an IC₅₀ value of 0.47 μM. Moreover, compound 46 displayed remarkable selectivity over prostate cancer cell line PC-3 with a selectivity index greater than 190-fold. Further cell-based mechanism studies revealed that compound 46 and lycobetaine can effectively induce G1 cell cycle arrest and apoptosis dose dependently. However, lycobetaine inhibited the expression of neuroendocrine markers, while compound 46 slightly upregulated these proteins. This suggested that compound 46 might exert its antitumor activities through a different mechanism than lycobetaine, warranting further study.