Natural products reverse cancer multidrug resistance.

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

Discovery of Novel Aminobutanoic Acid-Based ASCT2 Inhibitors for the Treatment of Non-Small-Cell Lung Cancer.

Alanine-serine-cysteine transporter 2 (ASCT2) is up-regulated in lung cancers, and inhibiting it could potentially lead to nutrient deprivation, making it a viable strategy for cancer treatment. In this study, we present a series of ASCT2 inhibitors based on aminobutanoic acids, which exhibit potent inhibitory activity. Two compounds, 20k and 25e, were identified as novel and potent ASCT2 inhibitors, with IC50 values at the micromolar level in both A549 and HEK293 cells, effectively blocking glutamine (Gln) uptake. Additionally, these compounds regulated amino acid metabolism, suppressed mTOR signaling, inhibited non-small-cell lung cancer (NSCLC) growth, and induced apoptosis. In vivo, experiments showed that 20k and 25e suppressed tumor growth in an A549 xenograft model, with tumor growth inhibition (TGI) values of 65 and 70% at 25 mg/kg, respectively, while V9302 only achieved a TGI value of 29%. Furthermore, both compounds demonstrated promising therapeutic potential in patient-derived organoids. Therefore, these ASCT2 inhibitors based on aminobutanoic acids are promising therapeutic agents for treating NSCLC by targeting cancer Gln metabolism.

Lophachinins A-E, abietane diterpenes from a Mongolian traditional herbal medicine Lophanthus chinensis.

Five new abietane diterpenes, lophachinins A-E (1-5), and eleven known related diterpenes were isolated from a Mongolian traditional herbal medicine, the aerial parts of Lophanthus chinensis (Lamiaceae). The structures of new diterpenes were assigned by spectroscopic analyses. Lophachinins A (1) and B (2) were abietane diterpene possessing an endoperoxy bridge at C-ring. In contrast, lophachinins C-E (3-5) had an abietane skeleton with an aromatized C-ring. The absolute configuration of 1 was elucidated by application of the modified Mosher's method, while those of 2, 3, and 5 were assigned by chemical conversions. The absolute configuration of lophachinin D (4) was deduced by ECD calculation. Anti-inflammatory activity of isolated diterpenes on microglial cells were evaluated.

A cross-sectional analysis of falsified, counterfeit and substandard medicines in a low-middle income country.

BACKGROUND: High prevalence of falsified, counterfeit and substandard medicines pose a threat to public health and treatment failure. This study aimed to investigate the quality of selected essential medicines available in Mongolia. METHODS: A cross-sectional study collected essential medicines from pharmacy outlets in Mongolia, during June and July, 2017. These products were then submitted for pharmacopoeial analysis and registration status. RESULTS: A total of 1770 samples from 118 pharmacy entities were purchased from wholesalers in urban and rural areas. Pharmacopoeial analysis found 179 (10.1%) samples or eleven product groups were unacceptable. The prevalence of substandard locally produced medicines (n = 105, 5.9%) was higher than imported equivalents [(n = 74, 4.17%, p = 0.0001)]. Approximately one-third of all unacceptable tests were related to assay (n = 73, 30.8%) and weight variation. Of 1770 samples, 76 (4.3%) were unregistered and the prevalence of unregistered samples was 3.8% in Ulaanbaatar city and 5.8% in rural areas, respectively. CONCLUSIONS: This study has indicated that falsified and substandard medicines are prevalent in Mongolia. Considerable effort is required by regulatory authorities, private manufacturers, as well as importers to increase the quality of essential medicines in Mongolia.

Linaburiosides A-D, acylated iridoid glucosides from Linaria buriatica.

Four previously undescribed acylated iridoid glucosides, linaburiosides A‒D, one undescribed iridoid, 7-deoxyiridolactonic acid, and one known acylated iridoid glucoside, iridolinarin C, were isolated from the aerial parts of a Mongolian traditional herbal medicine, Linaria buriatica. Linaburiosides A‒D had an acyl moiety corresponding to 7-deoxyiridolactonic acid. Detailed spectroscopic analyses of linaburiosides A‒D and 7-deoxyiridolactonic acid led to the assignment of their structures. The absolute configuration of 7-deoxyiridolactonic acid was elucidated by application of the PGME method; those of linaburiosides A‒D were assigned on the basis of chemical conversions, as well as application of the modified Mosher's method. The absolute configuration of iridolinarin C was also elucidated in this study. Anti-inflammatory and antiproliferative activities of isolated compounds and their derivatives were evaluated.

Tetrahydroxanthones from Mongolian medicinal plant Gentianella amarella ssp. acuta.

Two tetrahydroxanthones, 1,3,5S,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone (1) and 1,3,5R,8S-tetrahydroxy-5,6,7,8-tetrahydroxanthone (2), and six new tetrahydroxanthone glycosides, amarellins A-F (3-8), were isolated from the aerial parts of a Mongolian medicinal plant Gentianella amarella ssp. acuta (Gentianaceae). The structures of 1-8 were elucidated on the basis of spectroscopic analysis, chemical conversion, and ECD calculation. Amarellins A-C (3-5) were assigned as 8-O-ß-D-glucoside, 8-O-ß-D-xyloside, and 1-O-ß-D-glucoside of 1, respectively, while amarellins D-F (6-8) were elucidated to be 8-O-ß-D-xyloside, 1-O-ß-D-glucoside, and 3-O-ß-D-glucoside of 2, respectively.