Real-Time Biological Annotation of Synthetic Compounds
نویسندگان
چکیده
Organic chemists are able to synthesize molecules in greater number and chemical complexity than ever before. Yet, a majority of these compounds go untested in biological systems, and those that do are often tested long after the chemist can incorporate the results into synthetic planning. We propose the use of high-dimensional "multiplex" assays, which are capable of measuring thousands of cellular features in one experiment, to annotate rapidly and inexpensively the biological activities of newly synthesized compounds. This readily accessible and inexpensive "real-time" profiling method can be used in a prospective manner to facilitate, for example, the efficient construction of performance-diverse small-molecule libraries that are enriched in bioactives. Here, we demonstrate this concept by synthesizing ten triads of constitutionally isomeric compounds via complexity-generating photochemical and thermal rearrangements and measuring compound-induced changes in cellular morphology via an imaging-based "cell painting" assay. Our results indicate that real-time biological annotation can inform optimization efforts and library syntheses by illuminating trends relating to biological activity that would be difficult to predict if only chemical structure were considered. We anticipate that probe and drug discovery will benefit from the use of optimization efforts and libraries that implement this approach.
منابع مشابه
Divergent Synthesis and Real-Time Biological Annotation of Optically Active Tetrahydrocyclopenta[c]pyranone Derivatives
Sp3-rich compounds are underrepresented in libraries for probe- and drug-discovery, despite their promise of extending the range of accessible molecular shapes beyond planar geometries. With this in mind, a collection of single-enantiomer bicyclic, fused cyclopentenones underpinned by a complexity-generating Pauson-Khand cyclization was synthesized. A fingerprint of biological actions of these ...
متن کاملThe Antiglycation Ability of Typical Medicinal Plants, Natural and Synthetic Compounds: A Review
Given the prevalence of diabetes and the increasing number of diabetics, it is essential to find medicines to decrease the chronic complications of diabetes. Several studies have demonstrated that chronic hyperglycemia and its complications are directly related to protein glycation. Thus, identifying natural inhibitors to stop glycation of proteins may play a crucial role in managing the chroni...
متن کاملAdaptive neuro-fuzzy inference system (ANFIS) applied for spectrophotometric determination of fluoxetine and sertraline in pharmaceutical formulations and biological fluid
The UV-spectrophotometric method of analysis was proposed for simultaneous determination of fluoxetine (FLX) and sertraline (SRT). Considering the strong spectral overlap between UV-Vis spectra of these compounds, a previous separation should be carried out in order to determine them by conventional spectrophotometric techniques. Here, full-spectrum multivariate calibrations adaptive neuro-fuzz...
متن کاملSynthesis and Biological Significance of Some 2-Azetidinone Derivatives
A new series of N-[2-(1H-1,2,3-benzotriazol-1-yl)ethyl]-4-(substitutedphenyl)-3-chloro-2-oxo-1-iminoazetidine, compounds 4(a-j) were synthesized. The structures of all the synthesized compounds were confirmed by chemical and spectral analyses such as IR, 1H NMR, 13C NMR and FAB-Mass. The compounds 4(a-j) were screened for their antibacterial, antifungal and antitubercular activities and gave ac...
متن کاملStudy on Trend of Biodegradability of Phenolic Compounds During Photo-Fenton Advanced Oxidation Process
Phenolic acids constitute a major group of pollutants which are recalcitrant to common biological treatment. In this study synthetic wastewater containing a mixture of p-coumaric and p-hydroxybenzoic acids was evaluated for photo-Fenton pretreatment. The changes in biodegradability (ratio of biochemical oxygen demand to total organic carbon (TOC)) and mineralization (TOC removal) were monitored...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 138 شماره
صفحات -
تاریخ انتشار 2016