The Medicinal Chemistry in the Era of Machines and Automation: Recent Advances in Continuous Flow Technology

Abstract

Medicinal chemistry plays a fundamental and underlying role in chemical biology, pharmacology, and medicine to discover safe and efficacious drugs. Small molecule medicinal chemistry relies on iterative learning cycles composed of compound design, synthesis, testing, and data analysis to provide new chemical probes and lead compounds for novel and druggable targets. Using traditional approaches, the time from hypothesis to obtaining the results can be protracted, thus limiting the number of compounds that can be advanced into clinical studies. This challenge can be tackled with the recourse of enabling technologies that are showing great potential in improving the drug discovery process. In this Perspective, we highlight recent developments toward innovative medicinal chemistry strategies based on continuous flow systems coupled with automation and bioassays. After a discussion of the aims and concepts, we describe equipment and representative examples of automated flow systems and end-to-end prototypes realized to expedite medicinal chemistry discovery cycles.

The rise of continuous flow biocatalysis – fundamentals, very recent developments and future perspectives

“…Today, a variety of analytical techniques, tools and sensors for flow devices are available and applicable. 214 Among them, online high performance liquid chromatography (HPLC) is one of the most widely used analytical methods, which is easy to understand due to its high versatility and short implementation time. Other monitoring techniques being frequently used are real-time gas chromatography (GC) and mass spectroscopy (MS).…”

Harnessing artificial intelligence for the next generation of 3D printed medicines

“…Whereas ML does not require in-depth knowledge, provided a sufficient amount of data is available. Moreover, ML provides the opportunity for continuous processes, which has the potential to achieve intelligent 3DP automation [264,265]. Nevertheless, there is an opportunity for existing DoE, FEA and mechanistic modellers to exploit ML to further enrich their research.…”

Application of lung microphysiological systems to COVID-19 modeling and drug discovery: a review

“…This MPS device recreated an air–liquid interface, giving component cells a physiologically accurate microenvironment [ 115 ]. While pumpless and pump-driven microfluidics in MPS devices inherently simplify the bottleneck steps of liquid handling, integrating MPS with recent advances in automated liquid handling and continuous flow can further enhance throughput [ 166 – 168 ], as well as facilitate biocontainment for studying viral disease [ 138 ].…”