In Silico Screening of Philippine Fabaceae-Derived Phenolic Acids as Potential NAGZ (Β-Hexosaminidase) Inhibitors of Neisseria Gonorrhoeae (PDB ID: 6JTJ)

Abstract

Neisseria gonorrhoeae remains a leading sexually transmitted pathogen worldwide and poses a public health challenge due to rising antimicrobial resistance. This crisis underscores the need for alternative treatment options. In this study, phenolic acids from Philippine Fabaceae plants were evaluated as potential inhibitors of the NagZ protein, an enzyme essential for bacterial cell wall recycling and survival. A total of 388 Fabaceae species obtained from Co’s Digital Flora of the Philippines were screened based on reported phenolic acid content from existing journals and literature. Among these, 92 species were identified to contain documented phenolic acids, yielding a total of 37 distinct phenolic acids. In silico analyses included molecular docking, drug-likeness, ADMET profiling, and molecular dynamics simulations. Among the candidates, ellagic acid, 3,4-Di-O-caffeoylquinic acid, and 4-caffeoylquinic acid showed the strongest binding and favorable pharmacokinetic properties. These top-performing ligands were derived from: 3,4-di-O-caffeoylquinic acid was identified from the leaf of Cassia fistula, while 4-caffeoylquinic acid was obtained from the leaves of Medicago polymorpha. Ellagic acid was remarkably prevalent, found in the flowers of Caesalpinia pulcherrima, the pods of Parkia speciosa, and more. These findings highlight their potential as lead compounds, supporting further in vitro and in vivo validation against resistant gonorrhea.