Title:Recent Progress in Small Molecular Inhibitors of DNA Gyrase
Volume: 28
Issue: 28
关键词:
抗菌、DNA促旋酶、抑制活性、氟喹诺酮、环丙沙星、药效、细菌耐药性。
摘要:
Background: In the past few decades, with the abuse of antibiotics, bacterial
resistance has enhanced constantly. More and more super species of bacteria, which are
seriously threatening human health, have been discovered. Developing novel antibacterial
agents to overcome the drug-resistance is an urgent duty. We all know that blocking
the information-transfer of bacterial DNA and RNA is one of the effective ways to inhibit
bacterial growth. Therefore, as the indispensable enzyme for DNA replication and transcription,
DNA gyrase is one of the important targets for bacterial inhibitors. Accordingly,
many inhibitors of DNA gyrase have also been developed.
Methods: In this review, to highlight the recent progress in DNA gyrase inhibitors, the
study in this field over the past three years (2017-2019) was summarized and organized
based on their backbones or core moieties. Both of the subunits of DNA gyrase were taken
into consideration.
Results: These DNA gyrase inhibitors have been classified based on their backbones or
core moieties. After the comparison of the divided 14 categories, we could achieve some
clues for future modification. In particular, we found that benzodiazepines and naphthalene
heterocycles were the most common structures in the drug design. On the other
hand, isopropyl and cyclopropyl have also been used in drug design, which provides
more inspiration for the investigations. Except for GSK2140944, which has entered the
phase III clinical trial stage, other compounds here were not fully promulgated with their
optimal pharmacokinetic activity.
Conclusion: We briefly summed up the current situation and future challenges on this
topic. Through the discussion of the design strategies and drug effect, we hope that this
review can provide a focused direction for future researches.
