Open Source Drug Discovery: Highly Potent Antimalarial Compounds Derived from the Tres Cantos Arylpyrroles
The development of new antimalarial compounds remains a pivotal part of the strategy for malaria elimination. Recent large-scale phenotypic screens have provided a wealth of potential starting points for hit-to-lead campaigns. One such public set is explored, employing an open source research mechanism in which all data and ideas were shared in real time, anyone was able to participate, and patents were not sought. One chemical subseries was found to exhibit oral activity but contained a labile ester that could not be replaced without loss of activity, and the original hit exhibited remarkable sensitivity to minor structural change. A second subseries displayed high potency, including activity within gametocyte and liver stage assays, but at the cost of low solubility. As an open source research project, unexplored avenues are clearly identified and may be explored further by the community; new findings may be cumulatively added to the present work.
SCINDR - The SCience INtroDuction Robot that will Connect Open Scientists
This project will develop a way to connect, in real time, globally disparate researchers who are doing similar science so that they can work better and faster towards the development of new medicines.
The scientific literature already fulfils the role of notifying researchers about work that has been done, and social media has recently evolved to alert researchers to what is being done. While these new communication technologies simplify the collaborative process between widely distributed researchers, there still exists a major gap in efficient real time alerting and updating. We aim to automate an alert process so that, as a researcher records what they are doing in a natural way, they are immediately alerted to others around the world in real time who are working on related science.
Our system is built on the conceptual model of the machine understanding of human-generated content, used by social media platforms to generate alerts to further relevant content. The system we propose to build will understand the molecular information being recorded in a scientist’s notebook. It will then search both its own records and others in the public domain in order to introduce scientists where there may be mutual advantage - when two laboratories are working on similar molecules, assays or approaches, for example. To achieve this, we will build on a recently developed open source electronic lab notebook (ELN)to create the required component - the automated alerting service we call the SCience INtroDuction Robot, or SCINDR.
Rapid Generation of Complex Molecular Architectures by a Catalytic Enantioselective Dearomatization Strategy
A catalytic enantioselective dearomatization strategy can be used to convert readily assembled phenols into complex polycyclic ar- chitectures. By combining oxidative dearomatization of phenols bear- ing a pendent nucleophile with enantioselective secondary amine catal- ysis, high enantiomeric excesses were obtained for the natural product- like products.
Experiences with a researcher-centric ELN
Electronic Laboratory Notebooks (ELNs) are progressively replacing traditional paper books in both commercial research establishments and academic institutions. University researchers require specific features from ELNs, given the need to promote cross-institutional collaborative working, to enable the sharing of procedures and results, and to facilitate publication. The LabTrove ELN, which we use as our exemplar, was designed to be researcher-centric (i.e., not only aimed at the individual researcher's basic needs rather than to a specific institutional or subject or disciplinary agenda, but also able to be tailored because it is open source). LabTrove is being used in a heterogeneous set of academic laboratories, for a range of purposes, including analytical chemistry, X-ray studies, drug discovery and a biomaterials project. Researchers use the ELN for recording experiments, preserving data collected, and for project coordination. This perspective article describes the experiences of those researchers from several viewpoints, demonstrating how a web-based open source electronic notebook can meet the diverse needs of academic researchers.
Open source drug discovery – A limited tutorial
Open science is a new concept for the practice of experimental laboratory-based research, such as drug discovery. The authors have recently gained experience in how to run such projects and here describe some straightforward steps others may wish to take towards more openness in their own research programmes. Existing and inexpensive online tools can solve many challenges, while some psychological barriers to the free sharing of all data and ideas are more substantial.
Enantioselective α-Arylation of N-Acyloxazolidinones with Copper(II)-bisoxazoline Catalysts and Diaryliodonium Salts
A new strategy for the catalytic enantioselective α-arylation of N-acyloxazolidinones with chiral copper(II)-bisoxazoline complexes and diaryliodonium salts is described. The mild catalytic conditions are operationally simple, produce valuable synthetic building blocks in excellent yields and enantioselectivities, and can be applied to the synthesis of important nonsteroidal anti-inflammatory agents and their analogues.