Optimized arylomycins are a new class of Gram-negative antibiotics. Smith Peter A,Koehler Michael F T,Girgis Hany S,Yan Donghong,Chen Yongsheng,Chen Yuan,Crawford James J,Durk Matthew R,Higuchi Robert I,Kang Jing,Murray Jeremy,Paraselli Prasuna,Park Summer,Phung Wilson,Quinn John G,Roberts Tucker C,Rougé Lionel,Schwarz Jacob B,Skippington Elizabeth,Wai John,Xu Min,Yu Zhiyong,Zhang Hua,Tan Man-Wah,Heise Christopher E Nature Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts no new class of antibiotic with activity against Gram-negative bacteria has been approved in over fifty years. Natural products and their derivatives have a key role in combating Gram-negative pathogens. Here we report chemical optimization of the arylomycins-a class of natural products with weak activity and limited spectrum-to obtain G0775, a molecule with potent, broad-spectrum activity against Gram-negative bacteria. G0775 inhibits the essential bacterial type I signal peptidase, a new antibiotic target, through an unprecedented molecular mechanism. It circumvents existing antibiotic resistance mechanisms and retains activity against contemporary multidrug-resistant Gram-negative clinical isolates in vitro and in several in vivo infection models. These findings demonstrate that optimized arylomycin analogues such as G0775 could translate into new therapies to address the growing threat of multidrug-resistant Gram-negative infections. 10.1038/s41586-018-0483-6

Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents. Rodrigues Tiago,Sieglitz Florian,Bernardes Gonçalo J L Chemical Society reviews Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets. The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer. Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration. Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition. Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators. Importantly, the de-orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies. Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine. 10.1039/c5cs00916b

Fluorescent natural products as probes and tracers in biology. Duval Romain,Duplais Christophe Natural product reports Covering: 1985 up to the end of 2016Fluorescence is a remarkable property of many natural products in addition to their medicinal and biological values. Herein, we provide a review on these peculiar secondary metabolites to stimulate prospecting of them as original fluorescent tracers, endowed with unique photophysical properties and with applications in most fields of biology. The compounds are spectrally categorized (i.e. fluorescing from violet to the near infra-red) and further structurally classified within each category. Natural products selected for their high impact in modern fluorescence-based biological studies are highlighted throughout the article. Finally, we discuss aspects of chemical ecology where fluorescent natural products might have key evolutionary roles and thus open new research directions in the field. 10.1039/c6np00111d

Natural Products and Chemical Biology Tools: Alternatives to Target Epigenetic Mechanisms in Cancers. Lascano Santiago,Lopez Marie,Arimondo Paola B Chemical record (New York, N.Y.) DNA methylation and histone acetylation are widely studied epigenetic modifications. They are involved in numerous pathologies such as cancer, neurological disease, inflammation, obesity, etc. Since the discovery of the epigenome, numerous compounds have been developed to reverse DNA methylation and histone acetylation aberrant profile in diseases. Among them several were inspired by Nature and have a great interest as therapeutic molecules. In the quest of finding new ways to target epigenetic mechanisms, the use of chemical tools is a powerful strategy to better understand epigenetic mechanisms in biological systems. In this review we will present natural products reported as DNMT or HDAC inhibitors for anticancer treatments. We will then discuss the use of chemical tools that have been used in order to explore the epigenome. 10.1002/tcr.201800133