For over half a century, the carbazole skeleton has been the key structural motif of many biologically active compounds including natural and synthetic products. Carbazoles have taken an important part in all the existing anti-cancer drugs because of their discovery from a large variety of organisms, including bacteria, fungi, plants, and animals. In this article, we specifically explored the literature from 2012 to 2018 on the anti-tumour activities reported to carbazole derivatives and we have critically collected the most significant data. The most described carbazole anti-tumour agents were classified according to their structure, starting from the tricyclic–carbazole motif to fused tetra-, penta-, hexa- and heptacyclic carbazoles. To date, three derivatives are available on the market and approved in cancer therapy.

A new efficient total synthesis of the phenazine 5,10-dioxide natural products iodinin and myxin and new compounds derived from them was achieved in few steps, a key-step being 1,6-dihydroxyphenazine di-N-oxidation. Analogues prepared from iodinin, including myxin and 2-ethoxy-2-oxoethoxy derivatives, had fully retained cytotoxic effect against human cancer cells (MOLM-13 leukemia) at atmospheric and low oxygen level. Moreover, iodinin was for the first time shown to be hypoxia selective. The structure-activity relationship for leukemia cell death induction revealed that the level of N-oxide functionality was essential for cytotoxicity. It also revealed that only one of the two phenolic functions is required for activity, allowing the other one to be modified without loss of potency.

The rise of antimicrobial resistance (AMR) worldwide and the increasing spread of multi-drug-resistant organisms expressing metallo-β-lactamases (MBL) require the development of efficient and clinically available MBL inhibitors. At present, no such inhibitor is available, and research is urgently needed to advance this field. We report herein the development, synthesis, and biological evaluation of chemical compounds based on the selective zinc chelator tris-picolylamine (TPA) that can restore the bactericidal activity of Meropenem (MEM) against Pseudomonas aeruginosa and Klebsiella pneumoniae expressing carbapenemases Verona integron-encoded metallo-β-lactamase (VIM-2) and New Delhi metallo-β-lactamase 1 (NDM-1), respectively. These adjuvants were prepared via standard chemical methods and evaluated in biological assays for potentiation of MEM against bacteria and toxicity (IC) against HepG2 human liver carcinoma cells. One of the best compounds, 15, lowered the minimum inhibitory concentration (MIC) of MEM by a factor of 32-256 at 50 μM within all tested MBL-expressing clinical isolates and showed no activity toward serine carbapenemase expressing isolates. Biochemical assays with purified VIM-2 and NDM-1 and 15 resulted in inhibition kinetics with k/ K of 12.5 min mM and 0.500 min mM, respectively. The resistance frequency of 15 at 50 μM was in the range of 10 to 10. 15 showed good tolerance in HepG2 cells with an IC well above 100 μM, and an in vivo study in mice showed no acute toxic effects even at a dose of 128 mg/kg.

Antimicrobial resistance (AMR), and in particular antibacterial resistance, is an increasingly serious threat to global public health. AMR develops when a microorganism (bacteria, fungus, virus or parasites) no longer responds to a drug to which it was originally sensitive. [1][2] Antibiotics have an enormous impact on modern medicine. They are essential in the treatment of many human diseases such as urinary tract infections, wound infections, bloodstream infections, pneumonia, tuberculosis and they are a prerequisite for chemotherapy or surgery. Without harmonized and immediate worldwide action to develop agents countering highly resistant bacteria (e.g. Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus), the world is heading towards a post-antibiotic era in which common infections could once again become life threatening. [1][2] The increase in mortality with bloodstream infections caused by methicillin-resistant S. aureus (MRSA) and third-generation cephalosporin-resistant E. coli is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. [3][4] The introduction of more potent alternatives of existing antibiotics provides only temporary

New MBL inhibitor renders resistant Gram negative bacteria susceptible to carbapenems.

Phenazine is known to regroup planar nitrogen-containing heterocyclic compounds. It was used here to enhance the bioavailability of the biologically important compound iodinin, which is near insoluble in aqueous solutions. Its water solubility has led to the development of new formulations using diverse amphiphilic α-cyclodextrins (CDs). With the per-[6-desoxy-6-(3-perfluorohexylpropanethio)-2,3-di-O-methyl]-α-CD, we succeeded to get iodinin-loaded nanoformulations with good parameters such as a size of 97.9 nm, 62% encapsulation efficiency and efficient control release. The study presents an interesting alternative to optimizing the water solubility of iodinin by chemical modifications of iodinin.