Latest ArticlesThe metabolites produced by complex and diverse microorganisms are important resources for drug research and development. Using new targets to screen microbial metabolites, many anti-cancer drugs acting on different targets are discovered. Anti-tumor antibiotics acting on various targets and signaling pathways are important members in the study of specific targets for anti-tumor, and some anticancer antibiotics with potent antitumor activity are used as "warheads" of antibody-drug conjugates. Microbial-derived anti-tumor substances acting on different targets with high-efficiency "warheads" molecules are reviewed to provide a literature basis for research on the anti-cancer drugs for specific targets derived from microorganisms.
Due to the potent bactericidal activity and low incidence of drug resistance, the novel cyclic lipopeptide antibiotic - daptomycin has emerged as one of the first line antimicrobial agents in the treatment of serious infections caused by gram-positive resistant pathogens. This review summarizes the research advances of daptomycin in recent years, mainly including spectrum of antimicrobial activity, biosynthesis, mode of action, mechanism of drug resistance, structure-activity relationships, surotomycin and siderophore-daptomycin conjugate to kill multidrug resistant Acinetobacter baumannii. The findings summarized in this review highlight the directions of next-generation of daptomycin derivatives.
With the worldwide spread of multi-drug resistant (MDR) bacteria, bacterial resistance has become a major issue affecting human health. Although traditional methods for obtaining antibiotics by screening bacterial strains have found the most available antibiotics for us, this method has resulted in fewer and fewer antibiotics in the past few decades and is increasingly difficult to find the new structure of the compound entity. At present, there are few drugs that can fight super-resistant bacteria in the clinic or even research. therefore, the development and application of new technologies to address the issue of bacterial resistance is imminent. Since the first bacterial genome was sequenced more than 20 years ago, a large number of bacterial genomic sequence information can provide clues for the discovery of new antibiotics. In this review, we briefly outline the available data sources and highlight the use of genomic mining and metagenomics in discovery of new antibiotics.
Macrolide antibiotics have been widely utilized in the treatment of bacterial infections due to their strengths, low toxicity, and high efficacy. Because of the widespread application of macrolide drugs, the emergence of antibacterial resistance against antibiotics has become prominent. Ketolides, as the third generation macrolides, display improvement in activities against macrolide-resistant pathogens with broad antibacterial spectrum. Due to hepatotoxicity, the use of telithromycin has been limited. It is urgent to identify the novel sources of ketolides. So the structural modification of ketolides become the main research field of macrolide. This review introduces the recent progress in the structural modification of ketolide, with the purpose of providing support to development of new ketolide antibiotics.
Anti-tumor antibiotics exhibit great application potential in the anti-tumor therapy. Some drugs have become the first-line medication clinically. However, there are always various problems associated with anti-tumor antibiotics, such as poor solubility and instability as well as severe systemic side effects. It is important to choose suitable delivery carriers for a reasonable delivery system for a good targeting ability, enhanced anti-tumor efficacy and reduced adverse effects of the anti-tumor antibiotics, especially in the smart delivery systems. This review summarizes the carriers and the advances in the delivery systems of anti-tumor antibiotics, including anti-tumor antibiotic drugs currently on the market, in the clinical research stage and in the basic research stage.
Shikimate kinase is a key protein of the shikimic pathway, which is essential for the survival of Mycobacterium tuberculosis. In this study, a screening assay for Mycobacterium tuberculosis shikimate ki-nase (MtSK) inhibitor was developed. A 120 000-compound library was screened by the enzyme assay and the phenotype screening using Mycobacterium smegmatis. A hit compound named IMB-T5297[(E)-3-(3-(3-chloro-5-methoxy-4-(prop-2-yn-1-yloxy)phenyl)acryloyl)-6-methyl-2H-pyran-2, 4(3H)-dione] was identified to be a selective inhibitor of MtSK with a half maximal inhibitory concentration (IC50) value of 1.745 μg·mL-1, which also showed antibacterial activity. The interaction between compound and protein was analyzed by surface plasmon resonance (SPR) experiment, which showed the KD value was 2.151×10-5 mol·L-1. The binding model of MtSK and compound was simulated by the computer program. Five key amino acids in the binding pocket were indispensable site-directed mutated to verify the model. IMB-T5297 inhibited Mycobacterium tuberculosis H37Rv with a minimum inhibitory concentration (MIC) value of 49.723 μg·mL-1 and displayed low cytotoxicity to mammalian cells. In this study, IMB-T5297 was identified as a selective inhibitor of MtSK enzyme with anti-tuberculosis activity. With additional structural modification, the compound has a potential to become a novel anti-tuberculosis compound.
9-Acetoxycycloberberine (1) with a unique skeleton was first identified to display a potent antimicrobial profile against methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 1-16 μg·mL-1. Taking the compound as a lead, 14 target cycloberberine analogues with diverse structures, such as berberine and chelerythrine derivatives, were synthesized and evaluated for their anti-bacterial activities. Analysis of the structure-activity relationship revealed that:① ring E was essential for the activity; ② the removing of ring B decreased the activity against MRSA. However, the antimicrobial activity against vancomycin-resistant Enterococcus faecium (VRE) was improved; ③ the introduction of a suitable rigid substituent at the 9-position was beneficial for the activity. Among them, compound 9a showed the most potential activity against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA isolates with MIC values of 0.5-1 μg·mL-1, suggesting a different mechanism from clinical drugs. It displayed higher stability in blood. Therefore, we consider 9a worthy of further investigation. The results provide key scientific evidence for development of such compounds into a new type of anti-MRSA candidates.
Sansanmycins (SSs), produced by Streptomyces sp. SS, belong to uridyl peptide antibiotics which exhibit a good inhibitory effect on Mycobacterium tuberculosis and Pseudomonas aeruginosa. They share a unique chemical scaffold with a 4', 5'-enamide-3'-deoxyuridine attached to DABA (N-methyl-2, 3-diaminobutyryl) which was located in the peptide chain through peptide bond. In order to study the function of related genes and to employ synthetic biology to gain new SS derivatives, we obtained a complete SS biosynthetic gene cluster and heterologously expressed it in Streptomyces coelicolor M1146, M1152 and M1154. Fermentation broth of the recombinant strains were detected using HPLC and HPLC-MS/MS, and the result showed that SS-A was successfully produced in the three strains, and its production level in S. coelicolor M1154 was similar to the original wild type strain. In addition, a potential SS analogue named as SS-1154 was discovered from the fermentation broth of S. coelicolor M1154.
Circular RNA (circRNA) is a non-coding closed-loop single-stranded RNA molecule lacking the 5' end cap and the 3' poly (A) tail. Circular RNA is more abundant and stable than linear mRNA, and its expression is more conservative and specific. circRNA regulates cancer development through a variety of mechanisms, including miRNA sponges, regulating gene transcription, regulating RNA-binding proteins, and protein translation. This review summarizes the role of circRNA in cancer and helps to develop new clinical diagnostic techniques and treatments.
Aquaporin 1 (AQP1), the first water channel protein discovered among the aquaporin family, is a hydrophobic transmembrane protein involved in transcellular water movement. Recent evidence shows that AQP1 plays a role in tumor cell proliferation and migration, angiogenesis and tumor development and progression, representing a potential therapeutic target. In this review, we discuss the structures, functions and inhibitors of AQP1, as well as the involvement of AQP1 in tumor development and progression.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
