Scientia Pharmaceutica

29 pages, 3090 KB

Open AccessReview

From Antioxidants to Multi-Target Therapeutics: Preclinical and Emerging Evidence for Flavonoid Neuroprotection in Neurodegenerative Diseases

by Mohammad Khurshed Alam Khan, Pratikshya Paudel and Prabir Kumar Gharai

Sci. Pharm. 2026, 94(4), 89; https://doi.org/10.3390/scipharm94040089 - 1 Oct 2026

Abstract

Flavonoids are plant-derived polyphenols found in fruits, vegetables, tea and other dietary sources. Global dementia prevalence is projected to rise sharply, and current disease-modifying therapies remain limited in efficacy. This gap has contributed to growing interest in dietary flavonoids as multi-target neuroprotective agents. [...] Read more.

Flavonoids are plant-derived polyphenols found in fruits, vegetables, tea and other dietary sources. Global dementia prevalence is projected to rise sharply, and current disease-modifying therapies remain limited in efficacy. This gap has contributed to growing interest in dietary flavonoids as multi-target neuroprotective agents. This review draws together mechanistic, preclinical, and early clinical evidence for six flavonoid subclasses (flavanones, flavonols, flavones, flavanols, anthocyanins, isoflavones) across five neuroprotective mechanisms: antioxidant defense, suppression of neuroinflammation, inhibition of pathogenic protein aggregation, promotion of neurogenesis and synaptic density, and preservation of blood–brain barrier integrity. We also summarize proposed structure–activity relationships linking substitution patterns (catechol groups, hydroxylation, glycosylation) to these mechanisms. Most of this evidence comes from in vitro and rodent models. Longitudinal cohorts do link dietary intake to slower cognitive decline, but clinical trials remain few, early-phase, and inconsistent; some report negligible change on clinical metrics such as the UPDRS scale. Certain flavonoid metabolites are detected in rodent brain tissue after oral dosing, though whether humans achieve pharmacologically meaningful brain exposure at dietary or supplemental doses is still unresolved. Translation faces substantial barriers: limited oral bioavailability, extensive first-pass metabolism, inconsistent blood–brain barrier penetration, and wide inter-individual variability in metabolism, gut microbiome composition, and trial design. We close by outlining strategies, including nanoparticle delivery, prodrug design, and precision nutrition approaches, that could move flavonoids closer to clinical relevance. Full article

18 pages, 557 KB

Open AccessArticle

Lysosomal Exocytosis and Drug Resistance in K562 Cells

by Petr Mlejnek and Petr Dolezel

Sci. Pharm. 2026, 94(4), 88; https://doi.org/10.3390/scipharm94040088 - 29 Sep 2026

Abstract

Lysosomal exocytosis induced by the sequestration of hydrophobic weak-base drugs has been proposed as a mechanism of drug resistance (DR), although direct evidence for its quantitative relevance is lacking. Here, we compared the kinetics of lysosomal exocytosis with those of ABCB1-mediated active drug [...] Read more.

Lysosomal exocytosis induced by the sequestration of hydrophobic weak-base drugs has been proposed as a mechanism of drug resistance (DR), although direct evidence for its quantitative relevance is lacking. Here, we compared the kinetics of lysosomal exocytosis with those of ABCB1-mediated active drug efflux and passive drug efflux by diffusion in K562 cells. Drug panels were selected according to the process investigated, with passive efflux assessed using compounds representing both the lysosomal exocytosis and ABCB1 substrate groups. Lysosomal exocytosis was quantified using FITC-dextran-labelled lysosomes and flow cytometry. K562 cells with high or moderate ABCB1 expression were used to determine active efflux, whereas parental K562 cells lacking detectable ABCB1 expression were used to determine passive efflux. Drug-induced lysosomal exocytosis was slow, with the intracellular FITC-dextran content decreasing to approximately 50% of its initial value after 5–8 h at 30 μM and 8–12 h at 10 μM. In contrast, ABCB1-mediated and passive efflux exhibited half-times of approximately 12–20 and 23–36 min, respectively. Moreover, measurable lysosomal exocytosis occurred only at high micromolar drug concentrations associated with off-target cytotoxicity. Thus, lysosomal exocytosis is unlikely to represent a quantitatively relevant mechanism of drug resistance in K562 cells. Full article

12 pages, 2355 KB

Open AccessArticle

5-((5-Nitrofuran-2-yl)allylidene)-2-thioxo-4-thiazolidinones Target Microtubules in Breast Cancer Cells

by Magdalena Podolak, Rostyslav Dudchak, Agnieszka Gornowicz, Olga Klaudia Szewczyk-Roszczenko, Yegor Vassetzky, Małgorzata Borzym-Kluczyk, Krzysztof Bielawski, Roman Lesyk and Anna Bielawska

Sci. Pharm. 2026, 94(4), 87; https://doi.org/10.3390/scipharm94040087 - 29 Sep 2026

Abstract

4-Thiazolidinone derivatives, a group of compounds with a broad spectrum of activity and anticancer properties, are used in medicine as anti-inflammatory, antiviral, antibacterial, antidiabetic, and blood pressure-lowering drugs; some of them are now in phase II and III clinical trials as anticancer drugs. [...] Read more.

4-Thiazolidinone derivatives, a group of compounds with a broad spectrum of activity and anticancer properties, are used in medicine as anti-inflammatory, antiviral, antibacterial, antidiabetic, and blood pressure-lowering drugs; some of them are now in phase II and III clinical trials as anticancer drugs. Here, we evaluated the anticancer potential of 4-thiazolidinones (2b, 12b, 14b) targeting tubulin and metastasis-related pathways in breast cancer models. Molecular docking revealed that compound 14b exhibited the strongest binding affinity to the paclitaxel-binding site of β-tubulin, outperforming 2b and 12b, though slightly weaker than Taxol. Biological assays confirmed significant tubulin inhibition, with 14b reducing β-tubulin levels up to eight-fold in MCF-7 cells and two-fold in MDA-MB-231 cells. All compounds promoted tubulin polymerization, showing paclitaxel-like activity, with comparable the maximum velocity (V_max) values. Cell cycle analysis demonstrated G2/M arrest in MCF-7 cells and S-phase accumulation in MDA-MB-231 cells. Overall, compound 14b demonstrated the most promising multitarget anticancer activity in vitro. Full article

(This article belongs to the Special Issue Pharmaceutical Applications of Heterocyclic Compounds)

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21 pages, 1750 KB

Open AccessArticle

Design, Synthesis, and Cytotoxic Bioevaluations of Some Benzylidene Cinnamoylhydrazides

by Mohammad Hossain, Stephen M. Markley, Jaqueline Pena-Zacarias, Jacquelynn J. Wiles, Jolie N. Dionne, Renato J. Aguilera and Jonathan R. Dimmock

Sci. Pharm. 2026, 94(4), 86; https://doi.org/10.3390/scipharm94040086 - 28 Sep 2026

Abstract

Three series of benzylidene cinnamoylhydrazides (21 compounds) were synthesized and evaluated for cytotoxic activity against malignant and non-malignant cell lines. Among the compounds tested, 2d and 3c were the most active against Jurkat and CEM leukemia cells, with CC₅₀ values in the [...] Read more.

Three series of benzylidene cinnamoylhydrazides (21 compounds) were synthesized and evaluated for cytotoxic activity against malignant and non-malignant cell lines. Among the compounds tested, 2d and 3c were the most active against Jurkat and CEM leukemia cells, with CC₅₀ values in the low micromolar range. Both compounds were more potent against these leukemia cell lines than the reference compounds 5-fluorouracil, curcumin, and melphalan. However, 2d and 3c showed only modest selectivity over non-malignant Hs27 fibroblasts, with selectivity index values of 2.50 and 2.09, respectively, in CEM cells. Further studies in CEM cells showed that treatment with 2d and 3c was associated with apoptosis, caspase activation, increased ROS accumulation, mitochondrial membrane depolarization, and changes in cell-cycle distribution, with the most notable change being an increase in the sub-G0-G1 population. The compounds also showed growth-inhibitory and cytotoxic activity against several cell lines in the NCI-60 panel. Semi-empirical PM3 calculations suggested possible relationships between cytotoxic activity, electronic polarization of the α,β-unsaturated carbonyl system, and molecular dimensions. However, these relationships were not consistent across the series and should be considered preliminary. Overall, 2d and 3c represent useful hit structures for further investigation, although additional structural optimization and biological studies will be needed to improve their selectivity and better define their mechanisms of action. Full article

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21 pages, 2204 KB

Open AccessArticle

Discovery of First Quinoline–Acylguanidine Hybrids as Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Molecular Basis

by Mayara C. dos Santos, Átila M. Mofati, Nathalia F. Nadur, Larissa de A. P. Ferreira, Lucas Caruso, Gleyton L. S. Sousa, Renata B. Lacerda and Arthur E. Kümmerle

Sci. Pharm. 2026, 94(4), 85; https://doi.org/10.3390/scipharm94040085 - 24 Sep 2026

Abstract

Alzheimer’s disease (DA) remains a major therapeutic challenge, and selective butyrylcholinesterase (BChE) inhibition has emerged as a promising strategy for symptomatic treatment, particularly in advanced stages. Herein, a series of novel quinoline–acylguanidine hybrids was designed through a bioisosteric replacement of acridine–thiosemicarbazones and synthesized [...] Read more.

Alzheimer’s disease (DA) remains a major therapeutic challenge, and selective butyrylcholinesterase (BChE) inhibition has emerged as a promising strategy for symptomatic treatment, particularly in advanced stages. Herein, a series of novel quinoline–acylguanidine hybrids was designed through a bioisosteric replacement of acridine–thiosemicarbazones and synthesized via a convergent route combining the Pfitzinger reaction with acylguanidine formation. All derivatives were evaluated against BChE and AChE (acetylcholinesterase), and the 2-phenylquinoline derivative 2c (IC₅₀ = 7.14 µM) was identified as the most potent BChE inhibitor, comparable to donepezil (IC₅₀ = 2.39 µM), with selectivity over AChE. Structure–activity relationships revealed that the 2-phenyl substituent is essential for activity, whereas bulky groups (4-bromophenyl) or replacement with methyl abolished inhibition. Molecular docking showed that active compounds bind within the BChE catalytic anionic site with Trp110, Met465, and Trp458, while inactive analogs undergo a 180° flip of the quinoline scaffold, disrupting key interactions. In silico ADME evaluation indicated a favorable CNS drug-like profile (TPSA < 90 Å², LogBB > −1, no Lipinski violations, and no predicted P-glycoprotein substrate liability). These findings establish the quinoline–acylguanidine scaffold as a promising new chemotype for the development of selective BChE inhibitors with potential applications in Alzheimer’s disease. Full article

(This article belongs to the Special Issue Computer-Aided Drug Design and Molecular Synthesis)

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25 pages, 1052 KB

Open AccessReview

Approaches to the Development and Quality Control of Vaccine for Allergen-Specific Immunotherapy of Ragweed Pollen Allergy

by Taye Bello, Vladislav Turenko, Andrey Goryachev, Irina Remezova, Daniil Dolgov, George Pasikhov, Sergey Dementev, Vladimir Gegechkori, Yana Poskedova, Timofey Smirnov, Olga Petukhova, Musa Khaitov and Valery Smirnov

Sci. Pharm. 2026, 94(4), 84; https://doi.org/10.3390/scipharm94040084 - 24 Sep 2026

Abstract

Ragweed (Ambrosia artemisiifolia) pollen allergy is a major and growing public health problem worldwide, with clinical manifestations ranging from rhinitis and conjunctivitis to asthmatic episodes and anaphylaxis. The major ragweed allergen, Amb a 1, exhibits high IgE-binding potential and triggers type [...] Read more.

Ragweed (Ambrosia artemisiifolia) pollen allergy is a major and growing public health problem worldwide, with clinical manifestations ranging from rhinitis and conjunctivitis to asthmatic episodes and anaphylaxis. The major ragweed allergen, Amb a 1, exhibits high IgE-binding potential and triggers type 1 hypersensitivity reactions. Although allergen-specific immunotherapy (AIT) effectively induces long-term immune tolerance, conventional extract-based formulations face critical limitations including batch-to-batch variability, heterogeneous allergen composition, IgE-mediated adverse reactions, inconsistent immunogenicity, and poor patient compliance. This critical review synthesizes and evaluates published evidence on current synthetic vaccine strategies for ragweed AIT, with emphasis on their design, immunological performance, and quality control considerations. This review critically evaluates current approaches to synthetic vaccine development for ragweed AIT, with a particular focus on peptide-based constructs, recombinant proteins, DNA vaccines, and adjuvant-enhanced formulations, alongside corresponding quality control strategies. The available evidence indicates that synthetic vaccines provide a more rational, molecularly characterized trajectory for producing optimized AIT products with improved safety profiles, enhanced clinical efficacy, reduced injection frequency, and improved batch standardization relative to extract-based immunotherapy. These advances highlight the potential of synthetic vaccine platforms to support personalized immunotherapy and more effective disease-modifying treatment of allergic disorders. Full article

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24 pages, 10370 KB

Open AccessArticle

Antiplasmodial Potential of Compounds from the Bark of Mitragyna inermis (Rubiaceae): In Silico and In Vitro Studies Against LDH, PKG Enzymes and 3D7/Dd2 Strains

by Adelphe Dounia, Jean Noël Nyemb, Romeo Toko Feunaing, Cyrille Tchuente Djoko, Samiran Sadhukan, Sophie Laurent, Céline Henoumont and Emmanuel Talla

Sci. Pharm. 2026, 94(3), 83; https://doi.org/10.3390/scipharm94030083 - 20 Sep 2026

Abstract

Background: Plasmodium falciparum, the most virulent malaria parasite, continues to develop resistance to available drugs. Mitragyna inermis (Rubiaceae) is traditionally used in Africa for the treatment of malaria and has shown antiplasmodial activity against P. falciparum. Previous studies on this plant and [...] Read more.

Background: Plasmodium falciparum, the most virulent malaria parasite, continues to develop resistance to available drugs. Mitragyna inermis (Rubiaceae) is traditionally used in Africa for the treatment of malaria and has shown antiplasmodial activity against P. falciparum. Previous studies on this plant and related species (M. speciosa, M. ciliata) have focused on crude extracts and indole alkaloids, reporting moderate antiplasmodial activity, but the specific contribution of pure quinovic acid glycosides, the major triterpenes glycosides of M. inermis stem bark, to antiplasmodial activity and to inhibition of key parasite enzymes such as lactate dehydrogenase (PfLDH) and protein kinase G (PfPKG) has never been evaluated. Objective: The present study aimed to isolate and characterize compounds from the stem bark of M. inermis and to evaluate their antiplasmodial activity against Pf3D7 and PfDd2 strains and their binding potential to PfLDH and PfPKG through experimental and computational approaches. Methods: Phytochemical investigation was conducted using column chromatography, and structures were elucidated by ESI-MS and 1/2D NMR spectroscopy. Antiplasmodial activity was assessed against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfDd2) strains of P. falciparum. Molecular docking, ADMET prediction, and 100-ns molecular dynamics simulations targeting PfLDH and PfPKG were performed. Results: Five compounds were isolated and identified as quinovic acid 3-O-β-D-fucopyranoside (1), quinovic acid 3-O-β-D-glucopyranoside (2), quinovic acid 3β-O-β-D-fucopyranosyl-28-O-β-D-glucopyranosyl ester (3), olean-12-ene-3β,19β,24-triol (4), and lupeol-3-O-undecanoate (5). Compounds 4 and 5 are reported for the first time from the genus Mitragyna. Compound 3 exhibited the highest antiplasmodial activity against both PfDd2 (35.86 ± 0.83 μM) and Pf3D7 (29.89 ± 3.91 μM) strains, and showed the strongest binding affinity toward PfLDH (−8.2 kcal/mol). MD simulations confirmed the stability of the C3_PfLDH complex throughout the 100 ns simulation period. Conclusions: Compounds 1–4 displayed moderate in vitro antiplasmodial activity against Pf3D7 and PfDd2, with compound 3 being the most active among the isolated constituents. Docking and molecular-dynamics analyses suggested stable interactions of selected compounds with PfLDH and the PfPKG N-terminal cGMP-binding domain. However, these computational findings do not establish direct enzyme inhibition. The results support further investigation of M. inermis triterpenoids as phytochemical scaffolds, including cytotoxicity/selectivity testing, direct target-based assays and structural optimization. Full article

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22 pages, 8185 KB

Open AccessArticle

Development and Optimization of a Self-Nano-Emulsifying Drug-Delivery System (SNEDDS) of Ibuprofen by Implementing a Box–Behnken Experimental Design

by María José Jiménez, Keyner De La Cruz and Reinaldo G. Sotomayor

Sci. Pharm. 2026, 94(3), 82; https://doi.org/10.3390/scipharm94030082 - 20 Sep 2026

Abstract

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic, and anti-inflammatory activity; however, its low aqueous solubility limits its dissolution rate and, consequently, its oral bioavailability. This study aimed to develop and physicochemically characterize an ibuprofen-loaded self-nanoemulsifying drug delivery system [...] Read more.

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic, and anti-inflammatory activity; however, its low aqueous solubility limits its dissolution rate and, consequently, its oral bioavailability. This study aimed to develop and physicochemically characterize an ibuprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) using a Box–Behnken experimental design. Fifteen formulations were prepared and evaluated based on CQAs: cloud point, robustness to dilution, self-emulsification time, droplet size, zeta potential, and polydispersity index (PDI). The experimental responses were subjected to statistical analysis; robustness to dilution as the only response yielding a statistically valid and predictive model within the studied design space, which was used as the sole optimization criterion. The optimal formulation was evaluated and characterized according to previously established CQAs and subjected to thermodynamic stability testing and stress testing over one month. The optimized formulation exhibited rapid self-emulsification, with a self-emulsification time of 37.02 s, a cloud point of 64.87 °C, and high robustness to dilution across different pH conditions and dilution volumes. Moreover, it exhibited a mean droplet size below 157 nm, a zeta potential of −15.43 ± 0.58 mV, and a PDI of 0.251, suggesting adequate colloidal stability and uniformity of the dispersed system. These physicochemical attributes support the potential of the developed system as a platform for further biopharmaceutical evaluation of ibuprofen oral delivery. Full article

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17 pages, 1503 KB

Open AccessArticle

UHPLC-UV Method for Vancomycin Quantification in Human Plasma by Simple Protein Precipitation: Development and Validation for Therapeutic Drug Monitoring

by Joanne Palomino Saavedra, Yina Pájaro González, Donaldo de la Hoz Santander, Edwin Enrique Tenorio Jiménez, Orison Hernández Gámez and Gina Paola Domínguez Moré

Sci. Pharm. 2026, 94(3), 81; https://doi.org/10.3390/scipharm94030081 - 19 Sep 2026

Abstract

Vancomycin (VCN) is a glycopeptide antibiotic widely used to treat Gram-positive infections such as those caused by methicillin-resistant Staphylococcus aureus (MRSA). Its narrow therapeutic window, high interindividual pharmacokinetic variability, and dose-dependent nephrotoxicity support the need for therapeutic drug monitoring (TDM). In this study, [...] Read more.

Vancomycin (VCN) is a glycopeptide antibiotic widely used to treat Gram-positive infections such as those caused by methicillin-resistant Staphylococcus aureus (MRSA). Its narrow therapeutic window, high interindividual pharmacokinetic variability, and dose-dependent nephrotoxicity support the need for therapeutic drug monitoring (TDM). In this study, a UHPLC-UV method for VCN quantification in human plasma was developed and validated according to ICH M10 guidelines, using a one-step protein precipitation requiring only 100 µL of plasma. Clinical applicability was preliminarily explored in three hospitalized patients, where the area under the concentration-time curve over 24 h to minimum inhibitory concentration ratio (AUC₂₄/MIC) was estimated using PrecisePK, NextDose, and TDMx Bayesian software platforms before and after dose adjustment. The method showed linearity from 0.5 to 100 µg/mL (r² > 0.99), with accuracy within ±7% and precision below 11%. Acceptance criteria for selectivity and matrix effect were met, and stability was confirmed under multiple conditions, including clinically relevant storage and transport. Pre-adjustment AUC₂₄/MIC values were outside the target window of 400–600 in all patients, confirming the pertinence of implementing model-informed precision dosing as a routine TDM practice in Colombian health institutions. Full article

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28 pages, 3271 KB

Open AccessArticle

1,12-Bis-Triphenyl Phosphonium Dodecane Bromide Nanovesicles as Potential Inhibitors of MDR Staphylococcal Biofilms

by Silvana Alfei, Maria Luisa Cristina, Marina Sartini, Gianluca Ottria, Guendalina Zuccari, Caterina Reggio and Anna Maria Schito

Sci. Pharm. 2026, 94(3), 80; https://doi.org/10.3390/scipharm94030080 - 19 Sep 2026

Abstract

Multidrug resistance (MDR) has become a major global health threat, leading to the emergence of difficult-to-treat bacterial “superbugs” among both Gram-positive and Gram-negative species. In hospital settings, biofilm (BF)-producing staphylococci further aggravate this problem by markedly increasing tolerance to conventional antibiotics, thereby promoting [...] Read more.

Multidrug resistance (MDR) has become a major global health threat, leading to the emergence of difficult-to-treat bacterial “superbugs” among both Gram-positive and Gram-negative species. In hospital settings, biofilm (BF)-producing staphylococci further aggravate this problem by markedly increasing tolerance to conventional antibiotics, thereby promoting chronic and potentially life-threatening infections. In the present study, previously synthesized and characterized 1,12-bis-triphenyl phosphonium dodecane bromide nanovesicles (BPPB, 45 nm, water) were assayed by DLS in a medium (TSB), which was used for microbiologic tests, to assess the actual particle size (≈65 nm) existing in this biological setting, with PDI (0.37) and zeta potential (+6.1 mV). Although never investigated for its effects on the formation of staphylococcal BF, BPPB was, for the first time, evaluated as a potential novel agent to combat its development. A total of 12 highly BF-producing isolates from our collection, comprising six Staphylococcus aureus and six S. epidermidis strains, were selected because they are strong BF producers. Their full antibiogram was determined, and they were tested against BPPB to determine minimum inhibitory concentrations (MICs). Subsequently, BF inhibition activity was evaluated at ½ MIC, MIC, and 2× MIC concentrations. Vancomycin (V), used as a reference antibiotic, was tested under the same experimental conditions. BPPB exhibited MIC values ranging from 0.125 to 0.250 µg/mL, which were 1–8-fold lower than those of V. V did not inhibit BF formation by S. epidermidis at all and inhibited BF formation by Bam and Aam S. aureus isolates (96–97% inhibition) only at max concentrations (2 × MIC). Conversely, BPPB demonstrated potent and consistent inhibition activity against all strains, irrespective of species or resistance profile, as determined by VITEK. BF inhibition values of 83–99%, 95–>99%, and 98–>99% were observed at ½ MIC, MIC, and 2 × MIC, respectively. To confirm that BF inhibition did not arise from killing bacteria, determinations of bacterial colony count after BPPB treatment at 4 × MIC for 24 h were performed, establishing full vitality and a regrowth of 45% with respect to the inoculum. Once reseeded as in the control, treated bacteria grew exactly as the control. Overall, the findings confirmed the nanosized dimension of BPPB particles, which remained <100 nm, including in the complex biological medium; this highlighted the strong BF-forming capability and MDR phenotype of the selected staphylococcal isolates, as well as the remarkable antibacterial and BF inhibition efficacy of BPPB nanovesicles, significantly outperforming vancomycin. Importantly, the low cytotoxicity previously observed against eukaryotic Cos-7 and HepG2 cells, resulting in high selectivity index (SI) values (23.0–90.5), supports BPPB as a promising candidate for the development of new NM-based therapeutic strategies against MDR staphylococcal BF-associated infections. Full article

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17 pages, 1111 KB

Open AccessArticle

Structural Characterization and Cytotoxic Effects of Bioactive Compounds Isolated from Caulerpa sertularioides Against Human Cancer Cell Lines

by Edgar Sandoval-Petris, Rosalio Ramos-Payan, Hisila del Carmen Santacruz-Ortega, Maribel Plascencia-Jatomea, María Guadalupe Burboa-Zazueta, Idalia Osuna-Ruíz, Elsa Maribel Aguilar-Medina and Carmen María López-Saiz

Sci. Pharm. 2026, 94(3), 79; https://doi.org/10.3390/scipharm94030079 - 9 Sep 2026

Abstract

Compounds isolated from the macroalga Caulerpa sertularioides have been reported to exhibit cytotoxic activity. The objective of this study was to assess the antioxidant effects of compounds isolated from C. sertularioides as well as their antiproliferative effect against cancerous cell lines and to [...] Read more.

Compounds isolated from the macroalga Caulerpa sertularioides have been reported to exhibit cytotoxic activity. The objective of this study was to assess the antioxidant effects of compounds isolated from C. sertularioides as well as their antiproliferative effect against cancerous cell lines and to elucidate their chemical structure. The antiproliferative activity of C. sertularioides extracts was evaluated using the MTT standard assay in cancerous and non-cancerous cell lines. Morphological changes were observed via fluorescence microscopy, and the chemical structure of bioactive compounds was determined by nuclear magnetic resonance. Antioxidant activity was assessed using ABTS and DPPH methods. Among all extracts, the acetone extract exhibited the highest antioxidant activity (IC₅₀ of 27.3 ± 6.1 μg/mL) in the ABTS assay, which classifies it as a very potent antioxidant. Among the tested extracts, the hexane extract showed the strongest antiproliferative activity in breast (MDA-MB-231) and cervical cancer (HeLa) cell lines. The most active fraction (F15), obtained by open-column chromatography of hexane extract, exhibited the highest bioactivity against the MDA-MB-231 cell line (IC₅₀ of 55 ± 3.1 µg/mL); these cells exhibited morphological changes consistent with apoptosis. NMR analysis revealed signals tentatively assigned to 1-monolinolein, glycerol, bis(2-ethylhexyl) phthalate and bis(2-ethylhexyl) terephthalate. These findings support the potential of C. sertularioides as a source of bioactive compounds with antioxidant and antiproliferative properties. Full article

(This article belongs to the Special Issue Anticancer Potential of Natural Products)

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26 pages, 1173 KB

Open AccessReview

Monoclonal Antibody Therapies in Chronic Inflammatory Diseases: Periodontal Outcomes, Oral Safety, and Clinical Implications—A Scoping Review

by Adrian Stan, Sorina Nicoleta Munteanu, Alina Plesea-Condratovici, Liliana Mititelu-Tartau, Beatrice Rozalina Buca, Aurelia Romila, Liliana Lacramioara Pavel and Mihaela Moisei

Sci. Pharm. 2026, 94(3), 78; https://doi.org/10.3390/scipharm94030078 - 8 Sep 2026

Abstract

Monoclonal antibody-based therapies are widely used in chronic immune-mediated diseases, but their periodontal effects, dentoalveolar safety signals, and exposure characteristics remain incompletely characterized. This scoping review mapped periodontal clinical outcomes, biomarkers, microbiological and imaging findings, dentoalveolar safety, administration, treatment exposure, and pharmaceutical-context reporting. [...] Read more.

Monoclonal antibody-based therapies are widely used in chronic immune-mediated diseases, but their periodontal effects, dentoalveolar safety signals, and exposure characteristics remain incompletely characterized. This scoping review mapped periodontal clinical outcomes, biomarkers, microbiological and imaging findings, dentoalveolar safety, administration, treatment exposure, and pharmaceutical-context reporting. PubMed, Scopus, and Web of Science were searched in July 2026 without publication-year or language restrictions. Twenty-one reports representing 20 studies or cohort families were included. Evidence mainly concerned rheumatoid arthritis and therapies targeting tumor necrosis factor, interleukin-6 receptor, and cluster of differentiation 20. Evidence for interleukin-17A inhibition was insufficient and derived from one confounded five-patient case series. Tocilizumab showed the most consistent reductions in gingival inflammation and bleeding on probing, while structural changes were smaller and inconsistent. Tumor necrosis factor-directed findings were heterogeneous. Small rituximab studies showed favorable clinical or biomarker signals, whereas pharmacovigilance identified infectious and destructive dentoalveolar signals. Exposure reporting was incomplete, and no included periodontal study evaluated formulation stability, storage, cold-chain integrity, or handling deviations. This review integrates treatment-effect evidence, safety signals, and exposure variables across antibody targets and identifies a pharmaceutical–periodontal reporting gap requiring prospective investigation. Full article

(This article belongs to the Special Issue Monoclonal Antibodies in the Treatment of Diseases: Focus on Stability, Storage, and Administration)

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24 pages, 144769 KB

Open AccessReview

The Role of Phenolic Compounds in NF-κB, Nrf2, and STAT3 Transcription Factors Regulation: Therapeutic Potential and Limitations in Cancer Treatment

by Eirini Roungeri, Evangelia K. Konstantinou, Kallirroi Dimiza, Maria Dimitriou, Anastasios Darras and Athanasios A. Panagiotopoulos

Sci. Pharm. 2026, 94(3), 77; https://doi.org/10.3390/scipharm94030077 - 4 Sep 2026

Abstract

Cancer is still one of the major causes of death globally. While there are many cancer therapies, they often come with significant adverse effects and limitations. A lot of studies have shown that using natural products can improve the efficacy of conventional therapies [...] Read more.

Cancer is still one of the major causes of death globally. While there are many cancer therapies, they often come with significant adverse effects and limitations. A lot of studies have shown that using natural products can improve the efficacy of conventional therapies and decrease their toxicity. Natural products and their derivatives encompassing unmodified molecules, semi-synthetic analogs, and synthetic structures featuring natural pharmacophores, represent a major foundation for approved anticancer agents. Phenolic compounds are a large family of naturally occurring compounds found in plants and have attracted a lot of attention for their potential anticancer properties. Preclinical studies have shown that phenolic compounds have anticancer activity through different mechanisms, mainly by modulating inflammation, which plays a critical role in cancer development. Inflammatory processes in cancer involve complex molecular mechanisms regulated by both oncogenic and tumor-suppressing transcription factors. This review focuses on how phenolic compounds regulate transcription factors, such as nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and signal transducer and activator of transcription 3 (STAT3), which are critical in cancer-related gene expression, ultimately leading to the inhibition of cancer cell proliferation, invasion, and metastasis. Furthermore, phenolic compounds have been shown to synergize with conventional anticancer drugs, enhancing their efficacy and reducing side effects. This review investigates the role of phenolic compounds in regulating transcription factors in cancer animal models, highlighting both the therapeutic potential and limitations of these compounds in cancer prevention and treatment. Full article

(This article belongs to the Special Issue Anticancer Potential of Natural Products)

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14 pages, 23498 KB

Open AccessArticle

Translating the Properties of Physicochemical Dressings into Clinical Decision-Making for Heavily Exuding Wounds

by Paulina Sánchez-Toledo, Rosa M. Salgado, Silvestre Ortega-Peña and Edgar Krötzsch

Sci. Pharm. 2026, 94(3), 76; https://doi.org/10.3390/scipharm94030076 - 4 Sep 2026

Abstract

Introduction: Heavily exuding wounds can macerate perilesional skin and favour infection. Information on the properties and use time of dressings should be clear and available to healthcare providers. Methods: Our aim was to evaluate the updated series of the AQUACEL^® dressing family, [...] Read more.

Introduction: Heavily exuding wounds can macerate perilesional skin and favour infection. Information on the properties and use time of dressings should be clear and available to healthcare providers. Methods: Our aim was to evaluate the updated series of the AQUACEL^® dressing family, because their evolution from a single layer of carboxymethylcellulose (NaCMC) to a multicomponent antiseptic or its combination with polyurethane covered with a silicon layer has developed the technology beyond simple exudate absorption. Using gravimetric analysis, we evaluated the porosity, water uptake, and water vapour transmission rate (WVTR) of AQUACEL^® Ag+Extra, AQUACEL^® Foam, and Foam Pro. By modifying the method of measuring WVTR, we assessed this outcome during the progressive saturation of the dressings. We also performed a disc diffusion assay on agar to determine the antimicrobial effects of the dressings. Results: Independently of porosity, a second layer of cellulose in AQUACEL^® Ag+Extra doubles water uptake and quadruples WVTR compared to foam forms. When the different dressings were evaluated for WVTR under progressive saturation, we did not observe any statistically significant changes, indicating that retained liquids do not alter dressing properties, which is a more biologically suitable approach. Despite the acidic character of the cellulose hydrofibre contained in the three dressings, the lack of any antiseptics in the foam forms makes them unsuitable for use in colonised or infected wounds, although they can act as a physical barrier for microorganisms and mechanical damage. The opposite results were observed for the AQUACEL^® Ag+Extra dressing, which contains silver, EDTA, and benzethonium chloride. Discussion: Data on the physicochemical composition of dressings can enable healthcare providers to choose the appropriate dressing series to use during wound bed preparation and beyond. Full article

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17 pages, 29225 KB

Open AccessArticle

Integrated Pharmacognostic, LC-MS Metabolomic Profiling and Biological Evaluation of Elymus repens (L.) Gould

by Nyshanbay Konash, Jennyfer A. Aldana-Mejía, Sebastian John Adams, Kumar Katragunta, Kiran Kumar Tatapudi, Bharathi Avula, Ji-Yeong Bae, Ikhlas A. Khan, Galiya Sayakova, Kairat Zhakipbekov, Serzhan Mombekov and Samir A. Ross

Sci. Pharm. 2026, 94(3), 75; https://doi.org/10.3390/scipharm94030075 - 2 Sep 2026

Abstract

Elymus repens (L.) Gould has a long history of use in traditional medicine across the British Isles, particularly among Gaelic and Anglo-Saxon communities, where it has been employed as a diuretic and anti-inflammatory agent. Despite its ethnopharmacological significance, comprehensive insights into its phytochemical [...] Read more.

Elymus repens (L.) Gould has a long history of use in traditional medicine across the British Isles, particularly among Gaelic and Anglo-Saxon communities, where it has been employed as a diuretic and anti-inflammatory agent. Despite its ethnopharmacological significance, comprehensive insights into its phytochemical composition and biological activities remain limited. The present study aimed to provide an integrated characterization of E. repens through macro- and microscopic analyses, advanced phytochemical profiling, and evaluation of the biological activities of the rhizome part. Microscopic examination revealed distinct anatomical features differentiating rhizome and stem, leaf tissues, supporting accurate identification and pharmacognostic standardization. Chemical profiling using Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS) enabled the tentative identification of 93 metabolites, including amino acids, in aerial and rhizome extracts. These compounds were primarily classified into polyamines (e.g., feruloylputrescine, hydroxycoumaroylagmatine), phenolic acids (gallic, vanillic, and ferulic acids), flavonoids (apigenin, tricin, saponarin analogues), amino acids (arginine, tyrosine, tryptophan), organic acids (malic, succinic acids), nucleosides (adenosine, thymidine), and phospholipids. Biological evaluation demonstrated that the hydroethanolic rhizome extract exhibited notable antifungal activity against Aspergillus fumigatus (IC₅₀ = 34.9 µg/mL). Additionally, hydroethanolic extracts of both the aerial and rhizome parts showed no cytotoxicity in the Artemia salina lethality assay at concentrations up to 10 mg/mL, indicating a favorable preliminary safety profile. Of particular interest is tricin, which possesses anti-inflammatory, antioxidant, antimicrobial, and potential nephroprotective therapeutic effects; its mechanism of action is associated with the suppression of oxidative stress, the inhibition of pro-inflammatory mediators, and the disruption of metabolic processes in microbial cells. Overall, this study provides a comprehensive phytochemical and pharmacognostic characterization of E. repens, highlighting its potential as a source of bioactive compounds. The metabolite profile obtained directly from the biologically active extract, combined with its proven antifungal activity, serves as direct confirmation of the antimicrobial aspect of this plant’s traditional use, while its broader applications in ethnomedicine require targeted pharmacological testing. These findings contribute valuable data for chemotaxonomic classification and future pharmacological investigations. Full article

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18 pages, 26758 KB

Open AccessArticle

Potential Ligands to 3-Dehydroquinate Dehydratase (SaDHQD) of Staphylococcus aureus, Evaluated by Molecular Docking and In Vitro Assays to Develop an Antibiotic Drug

by Julio Cesar Armenta-Gorosave, Gerson Ney Hernández-Acevedo, Brenda Chimal-Vega, Donato A. Rechy Iruretagoyena, Ricardo Delgadillo-Valles and José Luis Vique-Sánchez

Sci. Pharm. 2026, 94(3), 74; https://doi.org/10.3390/scipharm94030074 - 31 Aug 2026

Abstract

The World Health Organization (WHO) estimates that by 2050, bacterial resistance will cause 10 million deaths, of which approximately one million are associated with multidrug-resistant (MDR) microorganisms. Staphylococcus aureus is one of the bacteria with high resistance to the most widely used antibiotics [...] Read more.

The World Health Organization (WHO) estimates that by 2050, bacterial resistance will cause 10 million deaths, of which approximately one million are associated with multidrug-resistant (MDR) microorganisms. Staphylococcus aureus is one of the bacteria with high resistance to the most widely used antibiotics that cause infections worldwide. Reports show that approximately 80% of S. aureus strains are resistant to penicillin (methicillin resistance), and that this resistance has been developing since the 1960s (WHO). On the other hand, there are new potential targets to develop new antibiotic drugs; notably, the 3-dehydroquinate dehydratase of S. aureus (SaDHQD) is relevant for this, due to the SaDHQD involved in the metabolism of the S. aureus, which is necessary in the shikimate pathway. This study proposes two compounds against SaDHQD to develop a new antibiotic drug. We performed in silico and in vitro assays for it, and in this way, this study proposes compounds that could be selected against SaDHQD, for the development of a new antibiotic drug. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

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18 pages, 1973 KB

Open AccessArticle

Native Tapioca Starch Agglomerated Using Its Gelatinized Dispersion for Tablet Production by Direct Compression

by Rapee Jarungsirawat, Chaipat Siriwachirachai and Thaned Pongjanyakul

Sci. Pharm. 2026, 94(3), 73; https://doi.org/10.3390/scipharm94030073 - 31 Aug 2026

Abstract

This study aimed to investigate the physical properties of native tapioca starch (TS) ag-glomerated using its gelatinized dispersion as an agglomerating agent and to evaluate the performance of the resulting agglomerate tablets. The results demonstrate that TS agglomerated with gelatinized tapioca starch (GTS) [...] Read more.

This study aimed to investigate the physical properties of native tapioca starch (TS) ag-glomerated using its gelatinized dispersion as an agglomerating agent and to evaluate the performance of the resulting agglomerate tablets. The results demonstrate that TS agglomerated with gelatinized tapioca starch (GTS) exhibited increased particle strength as GTS content increased. Moreover, particle flowability was enhanced compared with that of native TS. The compressibility of TS agglomerates increased with higher GTS content, thereby reducing resistance to volume reduction and enhancing the plasticity of particle deformation under pressure, resulting in the greater tensile strength of the tablets. GTS showed superior performance to polyvinylpyrrolidone and sodium alginate at the concentration of 2% w/w in terms of Carr’s index and tablet hardness. Propranolol HCl (PNL) tablets prepared from agglomerates with GTS exhibited higher hardness than those without GTS, with tablet hardness increasing proportionally to GTS content. Additionally, GTS facilitated faster tablet disintegration, thereby accelerating PNL dissolution. In drug-loading tests, agglomerate tablets containing 3% GTS maintained acceptable physical properties when the PNL content did not exceed 20% w/w. Higher PNL loading may be achievable by increasing compression pressure. These findings indicate that native TS agglomerated with GTS is a promising tablet diluent for direct compression. Full article

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27 pages, 2576 KB

Open AccessArticle

Development and Microstructural Analysis of Rapid-Release Acanthus montanus Effervescent Mouthwash Tablets for Oral Care

by Piyanut Thongphasuk, Nuntachai Hanpramukkun, Arthimond Vutthiphong, Ratana Charoenwattanasatien, Phakkhananan Pakawanit and Sucharat Limsitthichaikoon

Sci. Pharm. 2026, 94(3), 72; https://doi.org/10.3390/scipharm94030072 - 29 Aug 2026

Abstract

The translation of underutilized botanical resources into advanced therapeutic dosage forms represents a critical frontier in pharmaceutical sciences. This study systematically characterizes the phytochemical and biological profiles of three Acanthus species (Acanthus ebracteatus, Acanthus ilicifolius, and Acanthus montanus) to [...] Read more.

The translation of underutilized botanical resources into advanced therapeutic dosage forms represents a critical frontier in pharmaceutical sciences. This study systematically characterizes the phytochemical and biological profiles of three Acanthus species (Acanthus ebracteatus, Acanthus ilicifolius, and Acanthus montanus) to develop a functional, rapid-release effervescent mouthwash tablet for oral mucosal repair. Phytochemical screening demonstrated that ethanolic extraction selectively concentrated bioactive phenolics and saponins compared to conventional aqueous methods. The ethanolic A. montanus extract emerged as the premier candidate, exhibiting the highest total phenolic content, excellent biocompatibility with human gingival fibroblasts, and significant promotion of in vitro cellular migration. Furthermore, it demonstrated robust, broad-spectrum antimicrobial efficacy against key cariogenic (Streptococcus mutans) and opportunistic (Candida albicans) oral pathogens. To transition this botanical discovery into a viable delivery system, the optimized extract was integrated into an effervescent base via wet granulation utilizing absolute ethanol, followed by blending with extragranular excipients and single-stroke compression. The resulting optimized matrix, incorporating 10% sodium starch glycolate, achieved an ideal mechanical-kinetic balance, yielding exceptional structural toughness (0.23% friability) and rapid disintegration (2.02 min). Advanced 3D synchrotron X-ray tomographic microscopy revealed that this specific super-disintegrant ratio generates a highly interconnected, porous internal architecture driving accelerated capillary-mediated breakdown. Ultimately, this study successfully translates a botanical extract into a mechanistically optimized, functionally validated dosage form for targeted oral therapies. Full article

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33 pages, 7725 KB

Open AccessArticle

Phytochemical Study and Cytotoxic Properties of Hydroalcoholic Extracts of Epilobium parviflorum Schreb.: In Silico and In Vitro Insights

by Christian Goldiș, Roxana Racoviceanu, Mihaela Jorgovan, Roxana Negrea-Ghiulai, Codruța Șoica, Alexandra Prodea, Oana Bătrîna, Gabriela Antal and Alexandra Mioc

Sci. Pharm. 2026, 94(3), 71; https://doi.org/10.3390/scipharm94030071 - 23 Aug 2026

Abstract

Epilobium parviflorum Schreb. is a medicinal plant used traditionally against inflammatory disorders whose cytotoxic potential is still incompletely revealed. The current study investigates the phytochemical composition and in vitro cytotoxic activity of four hydroalcoholic extracts prepared from the aerial parts of E. parviflorum [...] Read more.

Epilobium parviflorum Schreb. is a medicinal plant used traditionally against inflammatory disorders whose cytotoxic potential is still incompletely revealed. The current study investigates the phytochemical composition and in vitro cytotoxic activity of four hydroalcoholic extracts prepared from the aerial parts of E. parviflorum by using maceration and Soxhlet extraction. The extracts were characterized in terms of total phenolic, flavonoid and tannins composition and LC-MS was used to identify its individual polyphenols. Their biological effects were assessed against four cancer cell lines (A375 melanoma, HT-29 colorectal adenocarcinoma, PANC-1 pancreatic carcinoma and SK-OV-3 ovarian adenocarcinoma cells), while using HaCaT keratinocytes as healthy cells in order to assess selectivity. Cell viability, cytoskeletal and nuclear morphology, mitochondrial respiration and network pharmacology were further investigated. A complex phenolic profile was revealed, with hyperoside being identified as the main component in all extracts while the extraction parameters strongly influenced the recovery of various phenolic compounds. All extracts reduced cancer cell viability in a dose-dependent manner after 24 h exposure, with the most pronounced effects observed at 720 and 1000 μg/mL, while HaCaT cells were left relatively unaffected. The morphological assessment indicated nuclear condensation, fragmentation and cytoskeletal disruption following the application of extracts. Moreover, high-resolution respirometry showed reduced oxidative phosphorylation and electron transfer system capacity thus indicating that early mitochondrial dysfunction may contribute to the cytotoxic effects. Network pharmacology revealed that ERBB2, CTNNB1, HSP90AA1 and HDAC6 might act as molecular targets in melanoma. Thus, these findings support the hypothesis that E. parviflorum hydroalcoholic extracts, particularly the 40% ethanol Soxhlet extract, may serve as important sources of bioactive phytocompounds with antiproliferative and apoptotic properties. Full article

(This article belongs to the Special Issue Anticancer Potential of Natural Products)

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