Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (βCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < −15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA–βCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9–2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0–100 ns). The conjugation with βCD improved the stability and decreased the mobility of all the residues (except residues 149–151) compared to FA–FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems.

Natural products remain a rich source of chemically diverse molecules with therapeutic potential, and Premna serratifolia represents one such promising botanical resource. This review provides a comprehensive overview of its bioactive constituents by integrating published evidence related to extraction variability, chemical profiling, physicochemical screening, and pharmacological activities. Available studies indicate that differences in extraction techniques influence the distribution of secondary metabolites, particularly phenolic and flavonoid compounds associated with biological activity. Previous phytochemical investigations have reported a structurally diverse set of compounds spanning multiple chemical classes. Evaluations based on drug-relevant parameters suggest that several constituents possess favorable structural and physicochemical characteristics. Published studies further suggest that selected compounds may interact with multiple protein targets involved in disease-related pathways. Computational evidence reported in the literature highlights potential molecular interactions and signaling networks associated with therapeutic activities. These pathways have been linked to biological processes such as cellular regulation, oxidative balance, and inflammatory responses. Available experimental evidence indicates that several compounds exhibit noteworthy bioactivities across different biological systems. Structural features, including functional group distribution and degree of substitution, have been reported to influence molecular interactions and pharmacokinetic properties. Simpler molecular frameworks often appear to show greater compatibility with drug-likeness criteria. The integration of phytochemical, pharmacological, and computational evidence provides a useful framework for compound prioritization and evaluation. Such an approach may facilitate the transition from phytochemical discovery toward pharmacological development. Further studies involving structural optimization, advanced computational modeling, and experimental validation are warranted to better characterize the therapeutic potential of these compounds. The available evidence suggests that Premna serratifolia is a valuable source of bioactive molecular scaffolds with considerable potential for future multitarget drug discovery and therapeutic development.

Pyrazoline benzenesulfonamide derivatives represent a distinctive class of heterocyclic compounds that synergistically combine the pharmacological versatility of the pyrazoline scaffold with the enzyme-inhibitory prowess of benzenesulfonamide moieties. These hybrids have emerged as promising candidates in anticancer drug discovery. This review systematically examines various synthetic strategies employed to prepare these derivatives, including classical Claisen–Schmidt condensation as well as modern ultrasound- and microwave-assisted protocols. These methods facilitate efficient structural diversification, incorporating a wide range of heterocyclic and aromatic substituents such as morpholine, pyrazole, benzodioxole, tetrazole, and ferrocene. Biological evaluations, integrating both in vitro cytotoxicity assays and in silico molecular docking studies, were analyzed to elucidate the anticancer potential and mechanistic insights of these compounds, particularly their selective inhibition of tumor-associated enzymes such as matrix metalloproteinases (MMP-2, MMP-9), carbonic anhydrase isoforms (hCA IX, hCA XII), and cyclooxygenase-2 (COX-2). The results reveal that several derivatives exhibit potent antiproliferative activity across multiple cancer cell lines, including lung (A549), breast (MCF-7), cervical (HeLa), colon (COLO 205), and oral squamous carcinoma, demonstrating significant tumor selectivity and low toxicity toward normal cells. Structure–activity relationship analyses further underscore the critical influence of electronic substituents and their positioning on aromatic rings in modulating both efficacy and selectivity. These findings highlight the therapeutic potential of pyrazoline benzenesulfonamide derivatives and support the continued optimization of synthetic strategies and mechanistic studies to facilitate their development as effective anticancer agents capable of overcoming clinical challenges such as drug resistance and adverse side effects.

Dengue virus infection is one of the health problems in tropical and subtropical countries. Although this disease is common, unfortunately, until now no licensed vaccine or relevant drugs available in the market. The first objective of this study is to design potent and selective peptidic inhibitors by studying the interactions between the designed peptides and the dengue NS2B/NS3 protease using computational docking technique and secondly to compare the quantitative and qualitative docking results using two independent docking programs (MOE and AutoDock 4.2). The proposed peptides were designed based on literature reviews and previous findings on the interaction between dengue NS2B/NS3 protease and reported peptides, thus, we designed ten cyclic tetrapeptides and twenty cyclic pentapeptides. The reported 3D structure of Wichapong and co-workers on the dengue NS2B/NS3 protease homology model was used in this study. The designed peptides were docked using MOE and AutoDock 4.2 softwares targeting dengue NS2B/NS3 protease. The results demonstrated that most of the proposed peptides were connected to the protease binding pocket and made interactions with the protease catalytic triad residues (His51, Asp75 and Ser135). Based on quantitative and qualitative docking results from the two docking programs, it showed that two cyclic tetrapeptides (1-C4 and 4-C4) and four cyclic pentapeptides (4-C5, 16-C5, 20-C5, and 6-C5) are the best potential inhibitors with the lowest free energy of binding and the high number of interactions with protease. In conclusion, the two independent docking programs could give almost the same results based on its quantitative and qualitative docking results. Thus, these potential peptides could serve as promising inhibitors for dengue virus. These findings will be further continued for the synthesis of these cyclic peptides and in vitro biological assays to confirm their activity.

Benzoylated α-mangostin derivatives demonstrated improved pharmacokinetic and toxicity profiles compared to the parent compound and doxorubicin. In silico screening identified AM-4-Nitrobenzoate, AM-3,5-Dinitrobenzoate, AM-4-Aminobenzoate, and AM-4-Trifluoromethylbenzoate as top candidates with lower binding energies and favorable interactions with key GSK3β residues. Molecular dynamics simulations confirmed stable complex formation, with RMSD values below 3.5 Å and reduced RMSF fluctuations at the catalytic pocket. MM-PBSA analysis highlighted AM-4-Nitrobenzoate as the most potent binder (ΔG_total −18.87 kcal/mol), followed by AM-4-Trifluoromethylbenzoate, AM-4-Aminobenzoate, and AM-3,5-Dinitrobenzoate, while α-mangostin and doxorubicin showed less favorable energies. Structural snapshots reinforced the persistence of ligand orientation and interactions, particularly for para-substituted derivatives. Overall, the integration of docking, MD simulation, and binding free energy analysis underscores para-substituted α-mangostin derivatives, especially AM-4-Nitrobenzoate, as promising scaffolds for GSK3β inhibition in the Wnt/β-catenin pathway relevant to triple-negative breast cancer.

Malaria is a life-threatening global disease, and despite artemisinin-based combination therapies (ACTs) as first-line treatment, emerging drug-resistant Plasmodium strains necessitate novel antimalarial agents. This study investigated the antiplasmodial potential of Eurycoma harmandiana Pierre (EH) root extract, a medicinal plant closely related to Eurycoma longifolia Jack (EL). The extract and its derived compounds were evaluated using in vitro antiplasmodial and cytotoxicity assays. The active compounds were further investigated by parasite morphological analysis, molecular docking against quadruple-mutant Plasmodium falciparum dihydrofolate reductase (qmPfDHFR), molecular dynamics (MD) simulations, and in silico prediction of drug-likeness, pharmacokinetic properties, and toxicity. The ethanolic extract exhibited potent antiplasmodial activity (IC₅₀ = 0.51 µg/mL) with low cytotoxicity (CC₅₀ = 31.68 µg/mL) and a high selectivity index (SI = 62.11). Quassinoids showed the strongest activity (IC₅₀ = 0.13–0.87 µM), whereas alkaloids displayed good to moderate activity. The extract and two promising bioactive quassinoids, eurycomanone (1) and glaucarubolone (5), disrupted intraerythrocytic parasite development. Molecular docking and MD simulations demonstrated that glaucarubolone (5) exhibited favorable predicted interactions with qmPfDHFR, along with favorable predicted drug-like properties, pharmacokinetic profiles, and low toxicity. This study provides the first report of the antiplasmodial activity of Eurycoma harmandiana, highlighting it as a promising alternative source of bioactive compounds against Plasmodium parasites. Glaucarubolone (5) may represent a promising scaffold for further investigation toward the development of novel antimalarial agents.