Mechanopharmacology: in vitro techniques to advance drug discovery.

Mechanopharmacology is an emerging interdisciplinary field that investigates drug action using biomechanically appropriate in vitro systems to the relevant (patho)physiology. This review outlines emerging technologies and techniques which aim to bridge the gap between mechanical cues influencing cellular biology and conventional pharmacology. We delve into the impact of mechanopharmacology on drug development in cancers and fibrotic diseases.

Dual-Purpose Aptamer-Based Sensors for Real-Time, Multiplexable Monitoring of Metabolites in Cell Culture Media.

The availability of high-frequency, real-time measurements of the concentrations of specific metabolites in cell culture systems will enable a deeper understanding of cellular metabolism and facilitate the application of good laboratory practice standards in cell culture protocols. However, currently available approaches to this end either are constrained to single-time-point and single-parameter measurements or are limited in the range of detectable analytes. Electrochemical aptamer-based (EAB) biosensors have demonstrated utility in real-time monitoring of analytes in blood and tissues.

A Homodimer of Withaferin A Formed by Base-Promoted Elimination of Acetic Acid from 27--Acetylwithaferin A Followed by a Diels-Alder Reaction.

Treatment of 27--acetylwithaferin A () with the non-nucleophilic base, 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), afforded 5β,6β-epoxy-4β-hydroxy-1-oxo-witha-2(3),23(24),25(27)-trienolide () and , a homodimer of withaferin A resulting from a Diels-Alder [4 + 2] type cycloaddition of the intermediate α,β-dimethylene-δ-lactone (). Structures of and were elucidated using HRMS and 1D and 2D NMR spectroscopic data. The structure of was also confirmed by single crystal X-ray crystallographic analysis of its -4---nitrobenzoate ().

Biosynthesis of Cytosporones in Leotiomycetous Filamentous Fungi.

Polyketides with the isochroman-3-one pharmacophore are rare among fungal natural products as their biosynthesis requires an unorthodox S-type aromatic ring cyclization. Genome mining uncovered a conserved gene cluster in select leotiomycetous fungi that encodes the biosynthesis of cytosporones, including isochroman-3-one congeners. Combinatorial biosynthesis in total biosynthetic and biocatalytic formats in and in vitro reconstitution of key reactions with purified enzymes revealed how cytosporone structural and bioactivity diversity is generated.