Garland Kgosi More

The scaffold concept is central in medicinal chemistry and drug design to generate, analyze, and capture the core structural frameworks that define bioactive compounds. Natural products and their underlying molecular scaffolds have long provided many of the biologically active ingredients in modern medicines and continue to inspire new therapeutic agents. However, linking these core structural frameworks to observed biological activity remains a key challenge in natural-product research. Here, this study integrates a computational-experimental approach combining scaffold-based drug analysis, chemical profiling, and computational and biological validation to identify bioactive motifs in Ceratonia siliqua L pods. A total of 253 identified compounds from the gas chromatography-mass spectrometry (GC-MS) profiling were clustered and grouped into antioxidant, antimicrobial, and cytotoxic activity sets, after which their Bemis-Murcko scaffolds were extracted using RDKit. The most common scaffolds were ranked and visualized to give a clear picture of the prevalent structural patterns throughout the data sets. Experimental assays validated the computational dominant scaffold predictions, revealing that the antioxidant activity was associated with phenolic and terpenoid scaffolds, the antimicrobial response was aligned with monoterpenoid and cyclohexane/cyclohexene-based scaffolds, and the cytotoxic trends were consistent with small heterocycles and imide-containing scaffolds. To further bridge the gap between the identified scaffolds and their corresponding biological activity, molecular docking was performed against key biological targets, including KEAP1, Staphylococcus aureus DHFR, and EGFR. The docking results demonstrated favorable binding interactions and identified key ligand-protein interactions, supporting the potential contribution of the GC-MS-identified compounds to the observed biological activities of the plant extract. These scaffold-activity relationships demonstrate that recurring structural motifs are associated with the biological effects observed in C. siliqua L., highlighting the plant as a promising source of pharmacologically relevant scaffolds for drug discovery.

Bioactive compounds from medicinal plants can enhance the therapeutic potential of trace metal–oxide nanoparticles. This study contributed to identifying the main volatile compounds and synthesizing manganese dioxide nanoparticles (MnO ₂ NPs) using Moringa oleifera ( MO ) leaf extract and explored their biological applications. Gas chromatography–mass spectrometry (GC–MS) analysis identified 21 volatile compounds with known bioactivities from the leaves of MO . Transmission electron microscopy (TEM) and x‐ray diffraction analysis showed that MnO ₂ NPs were spherical and crystalline, averaging ∼8.3 nm in size. Antioxidant activity, assessed by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) assays, revealed high potency (IC ₅₀ = 9.08 ± 0.11 and 6.62 ± 0.12 µg/mL). Cell viability assays indicated relative non‐toxicity, with IC ₅₀ values greater than 20 µg/mL for human embryonic kidney (HEK 293) and liver (HEPG2) cells. The antidiabetic effects were evaluated against α‐amylase and α‐glucosidase enzymes, showing IC ₅₀ values of 36.58 ± 0.74 and 55.03 ± 1.68 µg/mL, respectively, compared to FDA‐approved acarbose. Docking studies yielded scores of −6.10 and −7.32 kcal/mol. Overall, these results highlight that the MO ‐synthesized MnO ₂ NPs can be explored as potential antioxidant, cytoprotective, and antidiabetic agents for therapeutic uses.

Bioactive compounds from medicinal plants can enhance the therapeutic potential of trace metal-oxide nanoparticles. This study contributed to identifying the main volatile compounds and synthesizing manganese dioxide nanoparticles (MnO₂ NPs) using Moringa oleifera (MO) leaf extract and explored their biological applications. Gas chromatography-mass spectrometry (GC-MS) analysis identified 21 volatile compounds with known bioactivities from the leaves of MO. Transmission electron microscopy (TEM) and x-ray diffraction analysis showed that MnO₂ NPs were spherical and crystalline, averaging ∼8.3 nm in size. Antioxidant activity, assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, revealed high potency (IC₅₀ = 9.08 ± 0.11 and 6.62 ± 0.12 µg/mL). Cell viability assays indicated relative non-toxicity, with IC₅₀ values greater than 20 µg/mL for human embryonic kidney (HEK 293) and liver (HEPG2) cells. The antidiabetic effects were evaluated against α-amylase and α-glucosidase enzymes, showing IC₅₀ values of 36.58 ± 0.74 and 55.03 ± 1.68 µg/mL, respectively, compared to FDA-approved acarbose. Docking studies yielded scores of -6.10 and -7.32 kcal/mol. Overall, these results highlight that the MO-synthesized MnO₂ NPs can be explored as potential antioxidant, cytoprotective, and antidiabetic agents for therapeutic uses.

The Rift Valley fever virus (RVFV) poses a significant health threat, particularly in tropical and subtropical regions. Its symptoms include hemorrhagic fever and miscarriages, with no approved therapies available. A promising approach for treatment involves targeting host proteins that facilitate viral entry. Six bioactive caffeoylquinic acids were analyzed through molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT) against the RVFV LRP1(CR17) protein. Compounds 6 and 2 showed strong inhibitory potential with docking scores of ‐8.117 and ‐7.969 kcal/mol, respectively. The MD simulations indicated minimal deviation for these compounds, while specific protein interactions were identified. Compound 3 exhibited greater stability and lower reactivity, followed by compounds in the order: 1 > 2 > 4 > 6 > 5. Furthermore, the global electrophilicity index indicated that compound 3 (ω = 3.853 eV) is less electrophilic when accepting an electron, followed by 1 (ω = 4.192 eV), 6 (ω = 4.207 eV), 4 (ω = 4.302 eV), 2 (ω = 4.410 eV), and 5 (ω = 4.597 eV). These six caffeoylquinic acids can serve as lead compounds for drug design targeting RVFV entry proteins. Further in vitro and in vivo studies are needed to develop entry inhibitors against RVFV.

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a–d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF₃ or -OCF₃) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness.