Identification of valepotriate as a novel antimycobacterial agent against drug-resistant Mycobacterium tuberculosis through screening of a natural terpenoid compound library.
- 1Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
Abstract
Background
The continued emergence of multidrug-resistant Mycobacterium tuberculosis (M. tb) has substantially limited treatment options and highlights the need for new antimycobacterial agents. Although terpenoids comprise one of the largest classes of natural products with diverse biological activities, their antimycobacterial potential has not been systematically investigated.Methods
A library comprising 354 natural terpenoid compounds were screened against M. tb. Lead compounds were subsequently characterized by determining minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), time-kill kinetics, activity against clinical drug-sensitive and drug-resistant isolates, cytotoxicity in THP-1-derived macrophages and intracellular antimycobacterial activity using colony-forming unit assays.Results
Primary screening identified 10 compounds with strong antimycobacterial activity, among which valepotriate showed as a novel antimycobacterial agent. Valepotriate inhibited extracellular M. tb growth with an MIC of 10 μM and an MBC of 20 μM. Time-kill assays demonstrated rapid concentration-dependent bactericidal activity, reducing bacterial counts by >2 log₁₀ cfu within 24 h at 4× MIC and completely eradicating viable bacteria within 24 h at 8× and 16× MIC. Valepotriate retained activity against 14 clinical drug-sensitive and drug-resistant isolates with MIC values ranging from 5 to 20 μM. Valepotriate significantly reduced the intracellular bacterial burden at bactericidal concentrations that were well tolerated by THP-1-derived macrophages.Conclusions
Systematic screening identified valepotriate as a rapidly bactericidal antimycobacterial lead compound with activity against both drug-susceptible and drug-resistant M. tb, highlighting its potential as a natural product-derived scaffold for developing new antimycobacterial agents and motivating further optimization of its antibacterial potency.
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BibTeX
@article{zhu2026identification,
title = {{Identification of valepotriate as a novel antimycobacterial agent against drug-resistant Mycobacterium tuberculosis through screening of a natural terpenoid compound library.}},
author = {Chuanzhi Zhu and Xinyu Wang and Xinyue Zhang and Hongyan Jia and Lanyue Zhang and Zongde Zhang and Liping Pan},
journal = {JAC-antimicrobial resistance},
year = {2026},
month = nov,
doi = {10.1093/jacamr/dlag250},
url = {https://europepmc.org/article/MED/43011209},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Identification of valepotriate as a novel antimycobacterial agent against drug-resistant Mycobacterium tuberculosis through screening of a natural terpenoid compound library.
AU - Chuanzhi Zhu
AU - Xinyu Wang
AU - Xinyue Zhang
AU - Hongyan Jia
AU - Lanyue Zhang
AU - Zongde Zhang
AU - Liping Pan
PY - 2026
DA - 2026/11/10
JO - JAC-antimicrobial resistance
DO - 10.1093/jacamr/dlag250
UR - https://europepmc.org/article/MED/43011209
AB - Background The continued emergence of multidrug-resistant Mycobacterium tuberculosis (M. tb) has substantially limited treatment options and highlights the need for new antimycobacterial agents. Although terpenoids comprise one of the largest classes of natural products with diverse biological activities, their antimycobacterial potential has not been systematically investigated.Methods A library comprising 354 natural terpenoid compounds were screened against M. tb. Lead compounds were subsequently characterized by determining minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), time-kill kinetics, activity against clinical drug-sensitive and drug-resistant isolates, cytotoxicity in THP-1-derived macrophages and intracellular antimycobacterial activity using colony-forming unit assays.Results Primary screening identified 10 compounds with strong antimycobacterial activity, among which valepotriate showed as a novel antimycobacterial agent. Valepotriate inhibited extracellular M. tb growth with an MIC of 10 μM and an MBC of 20 μM. Time-kill assays demonstrated rapid concentration-dependent bactericidal activity, reducing bacterial counts by >2 log₁₀ cfu within 24 h at 4× MIC and completely eradicating viable bacteria within 24 h at 8× and 16× MIC. Valepotriate retained activity against 14 clinical drug-sensitive and drug-resistant isolates with MIC values ranging from 5 to 20 μM. Valepotriate significantly reduced the intracellular bacterial burden at bactericidal concentrations that were well tolerated by THP-1-derived macrophages.Conclusions Systematic screening identified valepotriate as a rapidly bactericidal antimycobacterial lead compound with activity against both drug-susceptible and drug-resistant M. tb, highlighting its potential as a natural product-derived scaffold for developing new antimycobacterial agents and motivating further optimization of its antibacterial potency.
SN - 2632-1823
ER -