Background: The glyoxylate shunt of fatty acid metabolism is critical to the survival of
Mycobacterium tuberculosis (Mtb) during the dormant stage. The two enzymes of glyoxylate shunt
pathway, isocitrate lyase (ICL) and malate synthase (MS), have been identified to be involved in Mtb
persistence and become the attractive targets to intervene with the pathway.
Methods: In order to search novel MS inhibitors, molecular docking in autodock Vina was employed
for the first time to virtually screen Fragment-Like subset of ZINC database against MS crystal structure.
Results: Total 11 candidates were screened out based on binding score, binding conformation, and
Conclusion: The interaction mode analysis, binding affinity reassessment and ADME predictions of
these candidates indicate they all can be treated as potential MS inhibitors. Their skeletons can be
classified into four novel types, i.e., pyrrolo[3,4-d]pyrimidine, chromen-2-one, hetero biphenyl and
phenyl substituted chiral cyclic diketone, which will bring an encouraging enlightenment to enrich the
category of MS inhibitors and broaden their research scope.