Two new meroterpenoids, aspergienynes O and P (1 and 2), one new natural compound, aspergienyne Q (3), and a new α-pyrone derivative named 3-(4-methoxy-2-oxo-2H-pyran-6-yl)butanoic acid (4) were isolated from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y85, along with five known compounds (5-9). The absolute configurations of those new isolates were confirmed through extensive analysis using spectroscopic data (HRESIMS, NMR, and ECD). The pharmacological study of the anti-proliferation activity indicated that isolates 5 and 9 displayed moderate inhibitory effects against HeLa and A549 cells, with the IC50 values ranging from 16.6 to 45.4 μM.

Quinoa, known as the \"golden grain\" for its high nutritional value, has polysaccharides as one of its sources of important nutrients. However, the biological functions of quinoa polysaccharides remain understudied. In this study, two crude polysaccharide extracts of quinoa (Q-40 and Q-60) were obtained through sequential precipitation with 40% and 60% ethanol, with purities of 58.29% (HPLC) and 62.15% (HPLC) and a protein content of 8.27% and 9.60%, respectively. Monosaccharide analysis revealed that Q-40 contained glucose (Glc), galacturonic acid (GalA), and arabinose (Ara) in a molar ratio of 0.967:0.027:0.006. Q-60 was composed of xylose (xyl), arabinose (Ara), galactose, and galacturonic acid (GalA) with a molar ratio of 0.889:0.036:0.034:0.020. The average molecular weight of Q-40 ranged from 47,484 to 626,488 Da, while Q-60 showed a range of 10,025 to 47,990 Da. Rheological experiments showed that Q-40 exhibited higher viscosity, while Q-60 demonstrated more elastic properties. Remarkably, Q-60 showed potent antioxidant abilities, with scavenging rates of 98.49% for DPPH and 57.5% for ABTS. Antibacterial experiments using the microdilution method revealed that Q-40 inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), while Q-60 specifically inhibited MRSA. At lower concentrations, both polysaccharides inhibited MDA (MD Anderson Cancer Center) cell proliferation, but at higher concentrations, they promoted proliferation. Similar proliferation-promoting effects were observed in HepG2 cells. The research provides important information in the application of quinoa in the food and functional food industries.

HSP90-CDC37 protein-protein interaction (PPI) works as a kinase specific-molecular chaperone system to regulate the maturation of kinases. Currently, selectively disrupting HSP90-CDC37 PPI, rather than the direct inhibition of the ATPase function of HSP90, is emerging as a promising strategy for cancer therapy by specifically blocking the maturation of kinases. However, due to the limited understanding of HSP90-CDC37 binding interface, design of small molecule inhibitors targeting HSP90-CDC37 PPI is challenging. In this work, based on the binding mode of compound 11 (previously reported by our group), we discovered a hydrophobic pocket centered on Phe213, which was previously unknown, contributing to the binding affinity of HSP90-CDC37 PPI inhibitors. A series of hydrophobic substituted inhibitors were utilized to confirm the importance of Phe213 hydrophobic core. Finally, we obtained an optimum compound DDO-5994 (exhibited an ideal binding pattern on hydrophobic core) with improved binding affinity (KD = 5.52 μM) and antiproliferative activity (IC50 = 6.34 μM). Both in vitro and in vivo assays confirmed DDO-5994 as a promising inhibitor to exhibit ideal antitumor efficacy through blocking HSP90-CDC37 PPI.

In order to improve the bioavailability of Oryza sativa L. anthocyanins, we fabricated Oryza sativa L. anthocyanins-Hohenbuehelia serotina polysaccharides (OSA-HSP) complex and investigated its anti-proliferation activities taking into account its changes along simulated gastrointestinal digestion in vitro. Results showed that OSA mainly composed by delphinidin, cyanidin, petunidin, malvidin and their derivatives was combined with HSP through electrostatic interaction. OSA-HSP complex belonged to non-crystalline substance, and had compact and laminar structural characteristics. Under simulated gastrointestinal digestion, OSA-HSP complex significantly prevented the degradation of anthocyanins, and presented sustain release effect. However, the anti-proliferation activities of OSA-HSP complex digested by different gastrointestinal process were remarkably changed, especially after small intestinal digestion. HeLa cells treated with OSA-HSP complex exhibited pro-apoptosis characteristics by triggering endogenous mitochondrial apoptosis pathway through activating the expressions of Bax, cytochrome c and Caspase-3 as well as inhibiting the expression of Bcl-2. These findings provided new insight to improve the bioavailability of anthocyanins in functional foods and tumor therapy.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase responsible for development of various tumor types. In this study, we synthesized a series of novel 2,4-diarylaminopyrimidine derivatives possessing a unique N-(3-pyridinylmethyl)urea moiety as ALK inhibitors. The most promising analog 5m bearing a 3-methoxy-4-morpholinophenyl substituent significantly inhibited proliferation of ALK positive H3122 and Karpas-299 cells with IC50 values about 10 nM, which were comparable with positive control LDK378. Compound 5m suppressed phosphorylation of ALK and its downstream proteins, and showed low cytotoxicity on normal human primary fibroblast cells (BJ cells). The binding mode of 5m was proposed by docking simulation, which explains the important role of N-(3-pyridinylmethyl)urea moiety. Furthermore, compound 5m exhibited favorable liver microsomal stability and significant efficacy in H3122 xenograft mice model. Interestingly, compound 5m also showed broader anti-proliferative activity on other human tumor cell lines, which was different from other ALK inhibitors.

Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC50 values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells.

Interferon (IFN)-λ, also known as IL-28A, IL-28B, or IL-29, is a new type III IFN, which shares many functional characteristics with type I IFN (α/β). Currently, IFN-α is used in the treatment of certain forms of cancer with severe adverse effects. Some researches had stated that IFN-λs induced a similar but restricted growth inhibition of tumor cells relative to IFN-α; moreover, mutations of IFN-λs could strongly impact its biological properties. In this study, three hIL-29 mutants (K33R, R35K, and K33R/R35K) were generated by site-directed mutagenesis and efficiently expressed in Pichia pastoris GS115, which have considerable abilities to inhibit the growth of BEL-7402, HCT-8, and SGC-7901 tumor cells in vitro. The results showed that these mutants (K33R, R35K, and K33R/R35K) exhibited a significantly enhanced anti-proliferation activity against these tumor cells, compared with native hIL-29 in vitro. Further assay in vitro indicated that superior to K33R and R35K, K33R/R35K had a significant increase in anti-tumor activity compared with IFN-α2b, which suggested that the K33R/R35K could make improvement for the effectiveness of native hIL-29 in clinic and could be used as a potentially powerful candidate for cancer immunotherapy.

Water-soluble polysaccharides (DCCP, DCPP) were extracted from the stems of Dendrobium chrysotoxum using boiling water and ultrasound. DCPP were successively purified by chromatography on DEAE-Cellulose-52 and Sephadex G-200 column, giving three major polysaccharide fractions termed DCPP-I, DCPP-I-a and DCPP-II. Among these fractions, DCPP-I-a exhibited the highest abundance (79.5%). The number-average molecular weight and weight-average molecular weight of DCPP-I-a were 67 kDa and 122 kDa, respectively. Monosaccharide components analysis indicated that DCPP-I-a were composed of xylose, glucose, galactose in a molar ratio of 1.44:6.93:12.79. Infrared spectra (IR) and (1)H NMR showed that DCPP-I-a was composed of a β-D pyran ring with a β-configuration. The evaluation of anti-proliferation activity suggested that DCPP-I-a and DCPP-II had a higher inhibitory effect on the SPC-A-1 cells than DCCP as determined with in vitro anti-proliferation test.