New mercaptoacrylate derivatives and other constituents from the stem bark of Senegalia polyacantha: in vitro antioxidant and antiplasmodial activities with in silico target validation
摘要
Antimalarial resistance remains one of the main obstacles in the fight against malaria, which continues to be a leading cause of death in Africa. This study aimed to evaluate the antiplasmodial, cytotoxic, and antioxidant properties of the extracts and compounds from the stem bark of Senegalia polyacantha (Willd.) Seigler & Ebinger (syn. Acacia polyacantha Willd.). The DCM/MeOH crude extract (SPDM) of S. polyacantha was further extracted with EtOAc (SPEA) and chromatographed, leading twenty-four compounds (1–24) which were all characterized using NMR and MS data. The SPDM, SPEA, and compounds (1–24) were assessed for their in vitro/in silico (PDB Id: 7QC1) antiplasmodial activities against asexual-blood stages of chloroquine-sensitive (3D7) and multiresistant (Dd2) strains of Plasmodium falciparum, as well as for their cytotoxic activities on Vero and RAW 264.7 and antioxidant potential using DPPH, ABTS, and FRAP assays. Compounds 1 and 2 were identified as previously unreported E/Z isomeric mercaptoacrylate derivatives, while compounds 3–24 were known. The antiplasmodial activity ranged from IC50 2.03 to > 50 μg/mL. Compound 17 was the most potent (2.03 μg/mL, 11.3 μM against 3D7; 3.08 μg/mL, 17.1 μM against Dd2), followed by 24 (2.50 μg/mL, 5.38 μM against 3D7; 5.05 μg/mL, 10.9 μM against Dd2). Antioxidant assays showed that 16 and 20 were the most active DPPH scavengers (IC50 9.8 and 9.7 μg/mL, respectively), while 21 exhibited the strongest reducing power (5120 μmol FeSO4/g). Cytotoxicity was low (CC50 56 to > 300 μg/mL), with selectivity indices > 10 for active compounds. Molecular docking against P. falciparum prolyl‑tRNA synthetase (PfProRS) suggested that compounds 4, 5, and 24 may interact with 7QC1 target (− 10.73, − 10.55, and − 7.42 kcal/mol, respectively), while ADME profiling indicated favorable drug‑like properties for 1/2. The tested samples showed limited cytotoxicity against Vero and RAW 264.7 cells for active compounds, and displayed potent antioxidant activities. These preliminary in vitro findings suggest that S. polyacantha stem bark extracts and isolated compounds possess antiplasmodial and antioxidant properties with favorable cytotoxicity profiles, warranting further in vivo studies to evaluate safety and therapeutic potential.