Cheminformatics-Guided Exploration of Synthetic Marine Natural Product-Inspired Brominated Indole-3-Glyoxylamides and Their Potentials for Drug Discovery.

Marine natural products (MNPs) continue to be tested primarily in cellular toxicity assays, both mammalian and microbial, despite most being inactive at concentrations relevant to drug discovery. These MNPs become missed opportunities and represent a wasteful use of precious bioresources. The use of cheminformatics aligned with published bioactivity data can provide insights to direct the choice of bioassays for the evaluation of new MNPs.

Synthesis and Cheminformatics-Directed Antibacterial Evaluation of Echinosulfonic Acid-Inspired Bis-Indole Alkaloids.

Synthetic efforts toward complex natural product (NP) scaffolds are useful ones, particularly those aimed at expanding their bioactive chemical space. Here, we utilised an orthogonal cheminformatics-based approach to predict the potential biological activities for a series of synthetic bis-indole alkaloids inspired by elusive sponge-derived NPs, echinosulfone A () and echinosulfonic acids A-D (-). Our work includes the first synthesis of desulfato-echinosulfonic acid C, an α-hydroxy bis(3'-indolyl) alkaloid (), and its full NMR characterisation.

Semisynthesis and Cytotoxic Evaluation of an Ether Analogue Library Based on a Polyhalogenated Diphenyl Ether Scaffold Isolated from a Sponge.

The known oxygenated polyhalogenated diphenyl ether, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol (), with previously reported activity in multiple cytotoxicity assays was isolated from the sponge sp. and proved to be an amenable scaffold for semisynthetic library generation. The phenol group of was targeted to generate 12 ether analogues in low-to-excellent yields, and the new library was fully characterized by NMR, UV, and MS analyses.

α-Synuclein Aggregation Inhibitory Procerolides and Diphenylalkanes from the Ascidian .

The aggregation of the neuronal protein α-synuclein (α-syn) is intrinsically linked to the development and progression of Parkinson's disease (PD). Recently we screened the MeOH extracts from 283 marine invertebrates for α-syn binding activity using an affinity mass spectrometry (MS) binding assay and found that the extract of the ascidian displayed activity. A subsequent bioassay-guided purification led to the isolation of one new α-syn aggregation inhibitory butenolide procerolide E () and one new α-syn aggregation inhibitory diphenylbutyrate methyl procerolate A ().

Facile dione protection to benzo[1,2-:6,5-']dithiophene-4,5-dione (BDTD) in triggering ultraviolet emission - A new member of the emissive 3,3'-bridged dithiophenes.

To date, 3,3'-bridged dithiophenes with bridges developed from the first period elements (either pristine or oxidised) are non emissive. Benzo[1,2-:6,5-']dithiophene-4,5-dione (BDTD) is a typical 3,3' fused-dithiophene with a dione bridge. It is a critical building block for semiconducting materials, and it is non emissive.