Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.

The trend toward designing large hydrophobic molecules for lead optimization is often associated with poor drug-likeness and high attrition rates in drug discovery and development. Structural simplification is a powerful strategy for improving the efficiency and success rate of drug design by avoiding \"molecular obesity\". The structural simplification of large or complex lead compounds by truncating unnecessary groups can not only improve their synthetic accessibility but also improve their pharmacokinetic profiles, reduce side effects and so on. This review will summarize the application of structural simplification in lead optimization. Numerous case studies, particularly those involving successful examples leading to marketed drugs or drug-like candidates, will be introduced and analyzed to illustrate the design strategies and guidelines for structural simplification.

The 2015 Nobel Prize in Physiology or Medicine has been awarded to avermectins and artemisinin, respectively. Avermectins produced by Streptomyces avermitilis are excellent anthelmintic and potential antibiotic agents. Because wild-type strains only produce low levels of avermectins, much research effort has focused on improvements in avermectin production to meet the ever increasing demand for such compounds. This review describes the strategies that have been widely employed and the future prospects of synthetic biology applications in avermectin yield improvement. With the help of genome sequencing of S. avermitilis and an understanding of the avermectin biosynthetic/regulatory pathways, synthetic and systems biotechnology approaches have been applied for precision engineering. We focus on the design and synthesis of biological chassis, parts, devices, and modules from diverse microbes to reconstruct and optimize their dynamic processes, as well as predict favorable effective overproduction of avermectins by a 4Ms strategy (Mine, Model, Manipulation, and Measurement).