Design, synthesis and anticancer activity of ß-carboline based pseudo-natural products by inhibiting AKT/mTOR signaling pathway.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains the leading cause of cancer deaths. Much progress has been made to treat NSCLC, however, only limited patients can benefit from current treatments. Thus, more efforts are needed to pursue novel molecular modalities for NSCLC treatment. It was demonstrated that pseudo-natural products (PNP) are a critical source for antitumor drug discovery. Herein, we describe a CH activation protocol for the expedient construction of a focused library utilizing the PNP rational design strategy. This protocol features a rhodium-catalyzed CH activation/ [4+2] annulation reaction between N-OAc-indole-2-carboxamide and alkynyl quinols, enabling facile access to diverse quinol substituted ß-carboline derivatives (31 examples). The anticancer activities were assessed in vitro against NSCLC cell line A549, yielding a potent antiproliferative ß-carboline derivative (8r) with an IC50 value of 0.8 ± 0.1 µM. Further investigation revealed that this compound could decrease the expression of Caspase 3, and increase the expression of autophagic protein Cyclin B1, thus markedly inducing autophagy and apoptosis. Mechanistic study suggested that 8r could be a potent anti-NSCLC agent through the AKT/mTOR signaling pathway in A549 cells. Moreover, the anticancer activities were also assessed against three other cancer cell lines, and 8r exhibits a broader inhibitory effect on cell proliferation in all cancer cell lines tested. These results indicated that carboline-based PNPs show great potential to induce cell autophagy and apoptosis, which serve as good leads for further drug discovery.

Symmetric cyanovinyl-pyridinium triphenylamine: a novel fluorescent switch-on probe for an antiparallel G-quadruplex.

In this study, we present a fluorescent switch-on probe based on a cyanovinyl-pyridinium triphenylamine (CPT) derivative that exhibited a 190-fold increase in fluorescence upon binding to G-quadruplex-forming oligonucleotide 22AG. This probe showed specificity and selectivity towards an antiparallel G-quadruplex, indicating its promising potential in G-quadruplex imaging.

[4 + 2] Cyclization or Lossen Rearrangement: Rhodium-Catalyzed Divergent Synthesis of Carboline Derivatives with Anticancer Activity.

An unusual rhodium-catalyzed C-H activation/Lossen rearrangement/oxa-Michael addition tandem cyclization has been achieved along with a tunable well-known C-H activation/[4 + 2] annulation, leading to regio-, chemo-, and diastereoselective access to diverse pentacyclic α-carbolines and ß-carboline-1-one derivatives in moderate to good yields with significant anticancer activity.

Development of a pH-activatable fluorescent probe and its application for visualizing cellular pH change.

Novel pH-activatable fluorescent probes with various pK(a) values have been developed utilizing 4-nitro-benzo[1,2,5]oxadiazole derivatives (NBD) as fluorophores and piperazine moieties as proton receptors. Under acidic conditions, probe FoPz displayed significant fluorescent enhancement of about 30 fold with a pK(a) value of 5.70 and it responds rapidly and sensitively to intracellular pH distributions and cellular pH fluctuations.

Sugarcane-Peanut Intercropping System Enhances Bacteria Abundance, Diversity, and Sugarcane Parameters in Rhizospheric and Bulk Soils.

Sugarcane-legume intercropping systems can effectively control pests and diseases as well as improve the fertility and health of farmland soil. However, little is known about the response of bacterial abundance, diversity, and community composition in the rhizosphere and non-rhizosphere soils under the sugarcane-peanut farming system. A field experiment was conducted with two treatments: sugarcane monoculture and sugarcane-peanut intercropping to examine the response of sugarcane parameters and edaphic factors. We also deciphered bacterial abundance, diversity, and community composition in the root endosphere, rhizosphere, and bulk soil by leveraging Illumina sequencing to conduct the molecular characterization of the 16S rRNA gene and nitrogenase (nifH) gene. We observed that sugarcane-peanut intercropping exhibited the advantages of tremendously increasing cane stalk height, stalk weight, and millable stalk number/20 m, and edaphic factors, namely, pH (1.13 and 1.93), and available phosphorus exhibited a fourfold and sixfold increase (4.66 and 6.56), particularly in the rhizosphere and bulk soils, respectively. Our result also showed that the sugarcane-peanut intercropping system significantly increased the bacterial richness of the 16S rRNA gene sequencing data by 13.80 and 9.28% in the bulk soil and rhizosphere soil relative to those in the monocropping sugarcane system, respectively. At the same time, sugarcane intercropping with peanuts significantly increased the Shannon diversity of nitrogen-fixing bacteria in the sugarcane rhizosphere soil. Moreover, most edaphic factors exhibited a positive regularity effect on bacterial community composition under the intercropping system. A linear discriminant analysis with effect size analysis of the 16S rRNA sequencing data revealed that bacteria in the root endosphere of the intercropped cane proliferated profoundly, primarily occupied by Devosia, Rhizobiales, Myxococcales, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Bradyrhizobium, and Sphingomonas. In conclusion, our findings demonstrated that sugarcane-peanut intercropping can enhance edaphic factors, sugarcane parameters, and bacterial abundance and diversity without causing adverse impacts on crop production and soil.