**5. Conclusions**

In this review, we introduced natural phenazines and synthetic phenazine derivatives, which were reported from 2012 to 2021. The biosynthetic pathways of natural phenazines, sources of microorganism and operon genes were illustrated in detail. Additionally, their pharmacological activities, mechanisms of action and structure–activity relationships were also summarized. In future studies, first of all, it is still necessary to find novel structures from natural sources for the screening of lead compounds. Secondly, it is very important to design and synthesize new compounds based on existing SAR through structural modification. The successfully applied drug clofazimine and XR11576, XR5944, NC-182 and NC-190 in clinical studies are good references. The structure modification at C-2, C-3, C-4 and N-6 sites and ring fused derivatives have a good prospect. In addition, target-based drug design can reduce the randomness. Finally, more extensive activity screening will enable more efficient use of compound resources.

**Author Contributions:** J.Y., investigation, visualization, writing—original draft, writing—review and editing; W.L., investigation, visualization, writing—review and editing; J.C., investigation, visualization, writing—original draft, writing—review and editing; Y.W., investigation, visualization, writing—original draft, writing—review and editing; D.L., funding acquisition, project administration, supervision, writing—original draft, writing—review and editing; H.H., project administration, supervision, writing—original draft, writing—review and editing; H.C., funding acquisition, project administration, supervision, writing—original draft, writing—review and editing. All authors have read and agreed to the published version of the manuscript.

**Funding:** This paper was financially supported by the Career Development Support Plan for Young and Middle-aged Teachers in Shenyang Pharmaceutical University.

**Conflicts of Interest:** The authors declare no conflict of interest.
