Targeting polyketide synthase 13 for the treatment of tuberculosis

Fei Xia; Haoling Zhang; Huanaoyu Yang; Mingming Zheng; Wenjian Min; Chengliang Sun; Kai Yuan; Peng Yang

doi:10.1016/j.ejmech.2023.115702

Targeting polyketide synthase 13 for the treatment of tuberculosis

Eur J Med Chem. 2023 Nov 5:259:115702. doi: 10.1016/j.ejmech.2023.115702. Epub 2023 Aug 1.

Authors

Fei Xia¹, Haoling Zhang¹, Huanaoyu Yang¹, Mingming Zheng¹, Wenjian Min¹, Chengliang Sun², Kai Yuan³, Peng Yang⁴

Affiliations

¹ State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
² State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. Electronic address: [email protected].
³ State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. Electronic address: [email protected].
⁴ State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China; Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing, 211198, China. Electronic address: [email protected].

PMID: 37544185
DOI: 10.1016/j.ejmech.2023.115702

Abstract

Tuberculosis (TB) is one of the most threatening diseases for humans, however, the drug treatment strategy for TB has been stagnant and inadequate, which could not meet current treatment needs. TB is caused by Mycobacterial tuberculosis, which has a unique cell wall that plays a crucial role in its growth, virulence, and drug resistance. Polyketide synthase 13 (Pks13) is an essential enzyme that catalyzes the biosynthesis of the cell wall and its critical role is only found in Mycobacteria. Therefore, Pks13 is a promising target for developing novel anti-TB drugs. In this review, we first introduced the mechanism of targeting Pks13 for TB treatment. Subsequently, we focused on summarizing the recent advance of Pks13 inhibitors, including the challenges encountered during their discovery and the rational design strategies employed to overcome these obstacles, which could be helpful for the development of novel Pks13 inhibitors in the future.

Keywords: Cell wall; Pks13 inhibitors; Structure-activity relationship; Tuberculosis.

Publication types

Review

MeSH terms

Antitubercular Agents / pharmacology
Antitubercular Agents / therapeutic use
Bacterial Proteins* / antagonists & inhibitors
Humans
Mycobacterium tuberculosis* / drug effects
Mycobacterium tuberculosis* / enzymology
Polyketide Synthases* / antagonists & inhibitors
Tuberculosis* / drug therapy
Tuberculosis* / microbiology

Substances

Antitubercular Agents
Polyketide Synthases
polyketide synthase Pks13, Mycobacterium tuberculosis
Bacterial Proteins