Antibacterial and Anticancer Activity, Acute Toxicity, and Solubility of Co-crystals of 5-Fluorouracil and Trimethoprim.

5-Fluorouracil is mainly used for the treatment of tumors and has relatively high toxicity. Trimethoprim is a common broad-spectrum antibiotic agent with extremely poor water solubility. We hoped to solve these problems by synthesizing co-crystals (compound 1) of 5-fluorouracil and trimethoprim. Solubility tests showed that the solubility of compound 1 was improved compared to that of trimethoprim. In vitro anticancer activity tests of compound 1 showed higher activity against human breast cancer cells than 5-fluorouracil. Acute toxicity showed that its toxicity was much lower than that of 5-fluorouracil. In the test of anti-Shigella dysenteriae activity, compound 1 showed much stronger antibacterial activity than trimethoprim.

The bioinformatics analysis of quercetin in octagonal lotus for the screening of breast cancer MYC, CXCL10, CXCL11, and E2F1.

BACKGROUND: Comprehensive bioinformatics analysis of the effective molecular screening of Podophyllum octagonal in breast cancer treatment by using network pharmacology. METHODS: We collected the active ingredients and target genes of Chinese medicine octagonal lotus through the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP); downloaded human protein annotation information on the protein database Uniport; and collected data from five databases: GeneCards, OMIM, PharmGkb, TDD, and DrugBank. Construct the practical ingredient-target gene data intersection to obtain the target gene-disease gene and draw the Venn diagram. We use Cytoscape 3.8.0 software to construct the effective component-target gene-disease gene network. The STRING database protein interaction (PPI) networks were erected, and we used Cytoscape 3.8.0 software to screen out its core sub-networks and hub gene networks. Through survival analysis, core genes and hub genes were screened to identify several key genes. We performed key target gene ontology (GO) analysis and gene interaction (KEGG) analysis, which were followed by molecular docking of the key active ingredients in the star anise corresponding to several key genes. RESULTS: 19 active ingredients, 444 drug targets, and 10,941 disease-related genes were obtained. The key active ingredient was quercetin. GO analysis revealed 2471 affected biological processes, and 167 pathways were obtained in KEGG enrichment analysis. CONCLUSION: This study initially screened the key active ingredients of star aniseed lotus and analyzed key genes and several essential pathways. Traditional Chinese medicine is expected to provide new evidence and research ideas to prevent and treat breast cancer.

Selective targeted delivery of doxorubicin via conjugating to anti-CD24 antibody results in enhanced antitumor potency for hepatocellular carcinoma both in vitro and in vivo.

PURPOSE: Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for clinical application. Cluster of differentiation 24 (CD24) is over-expressed in several human malignancies, especially in hepatocellular carcinoma (HCC). We aimed to develop a new class of CD24-targeted ADCs for HCC. METHODS: DOX was conjugated with G7mAb by a heterobifunctional cross-linker GMBS (N-[gamma-maleimido butyryloxy] succinimide ester) and further analyzed using HPLC. The targeting specificity and endocytosis of the newly generated ADC, G7mAb-DOX, were characterized using flow cytometry assay, near-infrared fluorescence imaging and laser scanning confocal microscope. The antitumor effects were evaluated in nude mice bearing HCC xenografts. RESULTS: G7mAb-DOX with average two drug molecules per antibody was selectively captured and endocytosed by CD24 (+) tumor cells in vitro. In vivo, the ADC was proved to target tumor tissues, suppress tumor growth and prolong the survival of HCC-bearing nude mice with improved efficacy and less systemic toxicity compared with either G7mAb or DOX single-agent treatment. CONCLUSION: These studies provide proof of concept for development of DOX-based ADCs which provide a novel approach for HCC-targeted immune therapy in clinical application.