Antimycobacterial Activity, Phytochemical Profile, and Molecular Docking of Compounds of Albizia Zygia (Dc.) J.F. Macrb

Abstract

Background: Tuberculosis (TB) remains a significant global health burden, exacerbated by increasing multidrug resistance. Medicinal plants, such as Albizia zygia (DC.) J.F. Macbr, is being used in Kenya to manage TB symptoms; however, antimycobacterial potential remains scientifically underexplored.
Methods: The root bark of A. zygia was sequentially extracted using hexane, dichloromethane, ethyl acetate, methanol, and water. Antimycobacterial activity against Mycobacterium smegmatis was assessed using the Microplate Alamar Blue Assay (MABA). Cytotoxicity was evaluated via the MTT assay on Vero cells, and synergistic interactions with rifampicin (RIF) were determined using a checkerboard assay. GC-MS was employed for phytochemical profiling, followed by molecular docking against Mycobacterium tuberculosis targets (pks13 and EthR) using Schrödinger 2023. ADME/T properties were also predicted using in silico studies.
Results: Methanol and aqueous extracts showed antimycobacterial activity with MIC₉₉ values of 625 μg/mL and 2500 μg/mL, respectively, and were non-cytotoxic (CC₅₀ >1000 μg/mL), except for the moderately cytotoxic dichloromethane extract. Synergistic and additive interactions with RIF were observed with FICI of 0.5 and 0.63, respectively. GC-MS identified 42 compounds; among which 7-ethyl-quinoline, diphenyl sulfone, hexa-decanoic acid, and 2,4-di-tert-butylphenol have been reported to exhibit antimycobacterial activity, also showed strong binding affinities (d-score ≥ -7.0 kcal/mol) to the multidrug resistance TB protein targets, Pks13 and EthR, suggesting their potential contribution to the observed antimycobacterial effects. ADME/T predictions indicated good oral bioavailability but raised concerns about CYP interactions and short terminal half-lives.
Conclusion: A. zygia root bark contains bioactive phytochemicals with promising antimycobacterial activity and synergism with rifampicin. These findings validate the ethnomedicinal use of A. zygia in TB management in Kenya; therefore, further in vivo evaluation and pharmacokinetic optimization of lead compounds are needed.