Scientia Pharmaceutica

43 pages, 15500 KB

Open AccessReview

Natural Products in Modern Drug Discovery: Advances, Challenges and Emerging Technologies

by Sousana K. Papadopoulou, Efthymios Poulios, Fotis Tsopelas, Anna Tsantili-Kakoulidou and Constantinos Giaginis

Sci. Pharm. 2026, 94(3), 61; https://doi.org/10.3390/scipharm94030061 - 16 Jul 2026

Abstract

Drug discovery is a complex and resource-intensive process, with lead identification representing a major bottleneck due to high attrition rates. Natural products have long served as a valuable source of structurally diverse and biologically active compounds, offering advantages such as evolutionary optimization, target [...] Read more.

Drug discovery is a complex and resource-intensive process, with lead identification representing a major bottleneck due to high attrition rates. Natural products have long served as a valuable source of structurally diverse and biologically active compounds, offering advantages such as evolutionary optimization, target specificity, and unique chemical diversity. This review provides a comprehensive and mechanistic overview of natural products as lead compounds, emphasizing their chemical characteristics, biological relevance, sources, mechanisms of action, and integration into modern drug discovery pipelines. A narrative review was conducted using major scientific databases (PubMed, Scopus, Web of Science, and Google Scholar), covering literature from 2000 to 2026. Relevant studies were selected based on scientific rigor and contribution to key themes, including natural product diversity, discovery strategies, and technological advancements. Natural products exhibit superior structural complexity and occupy unique chemical space compared to synthetic compounds, enabling effective interaction with diverse biological targets and supporting polypharmacological activity. Key sources include plants, microorganisms, and marine organisms, which have yielded numerous clinically important drugs. Advances in analytical techniques, genome mining, metabolomics, synthetic biology, and artificial intelligence have significantly improved discovery and optimization processes. Despite challenges related to complexity and scalability, natural products remain indispensable in drug discovery, with emerging technologies enhancing their potential for addressing unmet medical needs. Full article

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23 pages, 2858 KB

Open AccessArticle

Assessment of Anti-Influenza Activity of Pyrimidin-4(3H)-one Derivatives Using Prediction Models

by Yakov V. Gorokhov, Alexey D. Egorov, Nadezhda M. Andriyashina, Alexander N. Lobov, Irina S. Balashova, Aleksandrina S. Volobueva, Stanislav A. Grabovsky and Sophia S. Borisevich

Sci. Pharm. 2026, 94(3), 60; https://doi.org/10.3390/scipharm94030060 - 14 Jul 2026

Abstract

In this study, we used our own prediction models to assess the antiviral potential of pyrimidin-4(3H)-one derivatives against the A/H1N1 influenza virus strain. This assessment allows us to identify promising structures. The models are based on machine learning algorithms and molecular [...] Read more.

In this study, we used our own prediction models to assess the antiviral potential of pyrimidin-4(3H)-one derivatives against the A/H1N1 influenza virus strain. This assessment allows us to identify promising structures. The models are based on machine learning algorithms and molecular modeling results. In general, the prediction results are consistent with experimental data. The most promising compound, namely 12 (6-amino-2-(dimethylamino)pyrimidin-4(3H)-one), inhibits the reproduction of the A/Puerto Rico/8/34 (H1N1) influenza virus strain in vitro, likely by affecting the function of the endonuclease domain of the viral polymerase complex. Compound 12 can be used to create new PAN inhibitors by modifying its structure. Full article

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

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27 pages, 987 KB

Open AccessReview

Analytical Strategies for the Determination of Dapagliflozin in Pharmaceutical and Biological Matrices: A Comprehensive Review

by Ecaterina Gliga, Denisa Gabriela Stroia, Gabriel Hancu and Eleonora Mircia

Sci. Pharm. 2026, 94(3), 59; https://doi.org/10.3390/scipharm94030059 - 14 Jul 2026

Abstract

Dapagliflozin (DAPA), a selective sodium–glucose cotransporter 2 inhibitor, is widely used in the management of type 2 diabetes mellitus, with additional indications in heart failure and chronic kidney disease. The growing analytical demand for DAPA determination in pharmaceutical formulations, fixed-dose combinations, and biological [...] Read more.

Dapagliflozin (DAPA), a selective sodium–glucose cotransporter 2 inhibitor, is widely used in the management of type 2 diabetes mellitus, with additional indications in heart failure and chronic kidney disease. The growing analytical demand for DAPA determination in pharmaceutical formulations, fixed-dose combinations, and biological matrices has stimulated the development of diverse analytical methods. This review provides a comprehensive evaluation of reported techniques for DAPA quantification in different matrices. Approaches discussed include chromatographic methods (TLC, RP-HPLC, UHPLC, LC-MS/MS), electromigration techniques (CE), and spectroscopic methods (UV–Vis, spectrofluorimetry). Emphasis is placed on key performance characteristics such as selectivity, sensitivity, linearity, robustness, and applicability to stability studies and bioanalysis. Recent trends, including the application of Quality by Design, green analytical chemistry principles, and advanced hyphenated techniques, are also addressed. While RP-HPLC remains widely used for routine quality control due to its robustness and accessibility, LC-MS/MS is generally regarded as the method of choice for trace-level bioanalysis owing to its superior sensitivity and selectivity. CE and spectroscopic techniques offer cost-effective and environmentally friendly alternatives, though with certain limitations. This review highlights current methodological gaps and outlines future directions for developing more sensitive and sustainable analytical strategies. Full article

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37 pages, 5844 KB

Open AccessReview

A Brief Review of Synthetic Strategies of α-Pyrone-Based Phloroglucinol Derivatives from Helichrysum spp. and Structure–Activity Insights

by Yulian Voynikov, Konstantin Konstantinov, Iliyan Ivanov and Stanimir Manolov

Sci. Pharm. 2026, 94(3), 58; https://doi.org/10.3390/scipharm94030058 - 13 Jul 2026

Abstract

This review summarizes the synthesis and structural modification of α-pyrone-containing phloroglucinol derivatives from Helichrysum species. Synthetic routes to both natural products and synthetic analogues are covered, highlighting strategies ranging from β-keto ester cyclodehydration to multicomponent condensations. Key methods include aldehyde-mediated dimerization, [...] Read more.

This review summarizes the synthesis and structural modification of α-pyrone-containing phloroglucinol derivatives from Helichrysum species. Synthetic routes to both natural products and synthetic analogues are covered, highlighting strategies ranging from β-keto ester cyclodehydration to multicomponent condensations. Key methods include aldehyde-mediated dimerization, fluoride-catalyzed heterodimerization, and acid-catalyzed cyclization to benzopyran frameworks. The reported approaches enabled access to diverse monopyrone, dipyrone, arzanol-type, and cyclized analogues. Additionally, retrosynthetic analyses toward phloroglucinol–pyrone heterodimers are discussed, highlighting convergent synthetic strategies for future access to benzofurane-, chromene-, and chromane-based analogues. This review integrates published experimental data with newly generated in silico predictions. Full article

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28 pages, 3870 KB

Open AccessArticle

Targeting PD-1/PD-L1-MAPK1 Signaling by a Novel Synergistic Combination of Rivastigmine and Epigallocatechin in Alzheimer’s Disease: An Integrated In Silico Approach

by Bhaswati Das and Marakanam Srinivasan Umashankar

Sci. Pharm. 2026, 94(3), 57; https://doi.org/10.3390/scipharm94030057 - 10 Jul 2026

Abstract

This study investigates the synergistic therapeutic potential of Rivastigmine (RVG) and Epigallocatechin (EGC) in Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder characterized by neuroinflammation, oxidative stress, and dysregulated signaling pathways. Conventional therapies primarily provide symptomatic relief and target limited pathways, highlighting the need [...] Read more.

This study investigates the synergistic therapeutic potential of Rivastigmine (RVG) and Epigallocatechin (EGC) in Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder characterized by neuroinflammation, oxidative stress, and dysregulated signaling pathways. Conventional therapies primarily provide symptomatic relief and target limited pathways, highlighting the need for multi-target strategies with improved efficacy and safety. An integrated in silico approach combining pharmacokinetic evaluation, network pharmacology, molecular docking, and molecular dynamics simulations is used to determine the synergistic potential of RVG and EGC. Pharmacokinetic analysis indicates favorable drug-likeness and acceptable ADME/Tox profiles for both compounds. Network pharmacology identified 146 overlapping targets associated with AD, highlighting key hub genes including NFKB1, MAPK1, STAT1, PRKACA, GRB2, LYN, and PTPN11, which are involved in neuroinflammation, synaptic signaling, and neuronal survival. Functional enrichment analysis indicated significant involvement of MAPK/ERK signaling and immune-regulatory pathways. Importantly, the PD-1/PD-L1 signaling pathway is identified as a novel mechanism connecting neuroimmune modulation with intracellular kinase-driven neurodegeneration. Molecular docking studies showed strong binding affinities of RVG and EGC toward key AD-related targets, particularly MAPK1, supported by stable hydrogen bonding and interaction profiles. Molecular dynamics simulations confirmed stable protein-ligand interactions, with EGC contributing structural stability and RVG exhibiting adaptive flexibility within the binding pocket. These results suggest that the RVG-EGC combination exhibits synergistic potential by simultaneously modulating neuroinflammatory, oxidative stress, and kinase-mediated signaling pathways. The integration of PD-1/PD-L1 and MAPK/ERK signaling provides a novel mechanistic pathway for multi-target therapeutic intervention in AD. Full article

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

18 pages, 2013 KB

Open AccessArticle

Pharmaceutical Development and Characteristics of Orally Disintegrating Tablets with Dihydroquercetin Formulation Modifications

by Roman P. Terekhov, Maria D. Korochkina, Elizaveta V. Krivozubova, Grigory Yu. Evzikov, Artem A. Svotin, Maria N. Anurova and Irina A. Selivanova

Sci. Pharm. 2026, 94(3), 56; https://doi.org/10.3390/scipharm94030056 - 9 Jul 2026

Abstract

Oral diseases cause a wide range of difficulties for patients. The natural bioactive compound dihydroquercetin (DHQ), which demonstrates regenerative, anti-inflammatory, antioxidative, and antibacterial effects, is of interest for their treatment. The combination of DHQ and l-lysine DHQ is “very easily soluble”. The [...] Read more.

Oral diseases cause a wide range of difficulties for patients. The natural bioactive compound dihydroquercetin (DHQ), which demonstrates regenerative, anti-inflammatory, antioxidative, and antibacterial effects, is of interest for their treatment. The combination of DHQ and l-lysine DHQ is “very easily soluble”. The aim of this study is to compare orally disintegrating tablets based on raw DHQ and on the DHQ-l-lysine composition. Following the guidelines outlined in the ICH Q8 (R2) standard, a fundamental quality target product profile and critical quality attributes were established. The Sediment Delivery Model (SeDeM) method was used to evaluate the substance suitability for direct compression. Quantitative analysis of the DHQ release was carried out by high-performance liquid chromatography, and infrared (IR) spectroscopy was performed using the attenuated total reflection technique without any prior sample preparation. The DHQ-l-lysine composition shows improved dimensions (4.12) and flowability (4.96). The release rate constants (K_release) were 8.14 and 3.61%/min, while the half-release periods (t_50%) were 6.14 and 13.85 min for tablets with DHQ (TF1) and DHQ-l-lysine compositions (TF2), respectively. The difference factor (f₁) and similarity factor (f₂) were 23.43% and 43.37%, respectively. The tablet manufacture had a critical impact on the characteristics of the IR spectra (the r values −0.8785 and 0.5474 for TF1 and TF2). The conducted study demonstrates the promise of using DHQ-l-lysine composition for developing effective dosage forms with improved technological characteristics and controlled release of the active substance. Full article

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30 pages, 11501 KB

Open AccessReview

Current Challenges and Approaches to the Development of Novel Drug Products for Otic Administration: A Narrative Review

by Elena O. Bakhrushina, Natalia N. Mikhailova, Anastasia N. Golub, Ksenia V. Eremeeva, Anna-Daniela Koynova, Anna A. Popova, Andrey B. Goryachev, Olga I. Stepanova, Ivan I. Krasnyuk, Jr. and Ivan I. Krasnyuk

Sci. Pharm. 2026, 94(3), 55; https://doi.org/10.3390/scipharm94030055 - 5 Jul 2026

Abstract

Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported [...] Read more.

Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported annually worldwide, 51% of which occur in children. However, currently available topical otic formulations are limited by their inability to achieve predictable therapeutic concentrations at the site of inflammation, resulting in reduced efficacy. In addition, the selection of appropriate active pharmaceutical ingredients (APIs) for drug products remains challenging; as a result, existing therapies do not comprehensively address all stages of pathogenesis. This study aimed to analyze existing locally acting formulations for middle ear drug delivery, evaluate their advantages and limitations, and assess modern approaches to the development of novel drug delivery systems and API combinations. A critical review of 69 publications (2010–2026) was conducted, supplemented by a strengths and limitations analysis of dosage forms and an evaluation of APIs based on clinical data. The findings highlight a lack of targeted drug delivery systems, limited efficacy of existing API combinations against bacterial biofilms, and their risk of ototoxicity. Emerging innovative drug delivery approaches, including microemulsions, vesicular systems, stimuli-responsive systems, and hydrogels, have demonstrated promising results in preclinical studies; however, their efficacy and safety remain to be confirmed in clinical settings before their full therapeutic potential in otitis media treatment can be realized. Full article

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25 pages, 3191 KB

Open AccessArticle

Antinociceptive Activity of Petiveria alliacea L. Extract via GABAergic and Serotonergic Pathways in Diabetic Neuropathy Model

by Kelly del C. Cruz-Salomón, Alfredo Briones-Aranda, Abumalé Cruz-Salomón, Nancy Ruiz-Lau, Mariano Martínez-Vázquez, Joaquín A. Montes-Molina, Gerardo Leyva-Padrón, Josue V. Espinosa-Juárez and Rosa I. Cruz-Rodríguez

Sci. Pharm. 2026, 94(3), 54; https://doi.org/10.3390/scipharm94030054 - 2 Jul 2026

Abstract

Petiveria alliacea L. (commonly known as “anamu,” “guiné,” “hierba de zorro,” and “tipi”) has been widely used in Mesoamerican traditional medicine to treat pain and inflammation. However, scientific evidence supporting its efficacy in diabetic neuropathy remains limited. This study evaluated the antinociceptive potential [...] Read more.

Petiveria alliacea L. (commonly known as “anamu,” “guiné,” “hierba de zorro,” and “tipi”) has been widely used in Mesoamerican traditional medicine to treat pain and inflammation. However, scientific evidence supporting its efficacy in diabetic neuropathy remains limited. This study evaluated the antinociceptive potential of a methanolic leaf extract of P. alliacea in a murine model of alloxan-induced diabetic neuropathy and investigated its possible mechanisms of action. Diabetic CD-1 mice were evaluated for mechanical allodynia and hyperalgesia using the Von Frey test and for tonic pain using the formalin test. Pharmacological antagonists were administered to assess the involvement of opioid, nitric oxide, serotonergic, and GABAergic pathways. Phytochemical profiling was performed by LC-ESI-MS/MS, and potential pharmacological and pharmacokinetic properties of the identified metabolites were predicted using in silico tools (PASS online, SwissTargetPrediction, SwissADME, and pkCSM). The methanolic extract significantly reduced mechanical allodynia and hyperalgesia in diabetic mice and attenuated nociceptive responses in both phases of the formalin test, showing an effect comparable to gabapentin. Antinociceptive activity was not altered by naloxone or L-NAME but was significantly attenuated by methiothepin and bicuculline, suggesting that serotonergic and GABAergic pathways contribute, at least in part, to the observed antinociceptive effects. LC-ESI-MS/MS analysis identified 38 metabolites, including flavonoids, alkaloids, and terpenes, with in silico predictions supporting their potential analgesic and anti-inflammatory activities. The methanolic leaf extract of P. alliacea exhibits significant antinociceptive activity in diabetic neuropathy, partially likely to involve serotonergic and GABAergic mechanisms, supporting its ethnomedicinal use and its potential as a source of novel analgesic agents. Full article

(This article belongs to the Topic Natural Products and Drug Discovery—2nd Edition)

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23 pages, 6079 KB

Open AccessArticle

Development of a Rationally Designed siRNA-Based Therapeutic Targeting PD-L1 in Triple-Negative Breast Cancer

by Vivany Maydel Sierra-Sánchez, Sergio Adrian Ocampo-Ortega, Santiago Villafaña-Hernandez, Elvia Mera Jiménez, Rolando Alberto Rodríguez Fonseca, Asdrubal Aguilera-Méndez, Rodrigo Romero-Nava, Enrique Hong, Martha Edith Macías-Pérez and Santiago Villafaña

Sci. Pharm. 2026, 94(3), 53; https://doi.org/10.3390/scipharm94030053 - 30 Jun 2026

Abstract

In triple-negative breast cancer (TNBC), immune checkpoint pathways play a central role in tumor immune evasion. Programmed death protein 1 (PD-1) is an inhibitory receptor expressed on T cells, while its ligand, programmed death-ligand 1 (PD-L1), is commonly expressed on tumor cells and [...] Read more.

In triple-negative breast cancer (TNBC), immune checkpoint pathways play a central role in tumor immune evasion. Programmed death protein 1 (PD-1) is an inhibitory receptor expressed on T cells, while its ligand, programmed death-ligand 1 (PD-L1), is commonly expressed on tumor cells and cells within the tumor microenvironment. Their interaction suppresses T-cell activation and promotes immune escape. In this study, we evaluated the potential of small interfering RNA (siRNA) to silence PD-L1 expression in TNBC. Transcriptomic analysis of GEO datasets revealed consistent upregulation of CD274 (PD-L1) in TNBC samples. Three siRNA candidates were designed and evaluated in MDA-MB-231 cells. All siRNAs significantly reduced CD274 expression (>70%), as determined by RT-qPCR. Immunofluorescence analysis confirmed a reduction in PD-L1 protein levels (54.3 vs. 98.7 a.u.), while MTT assays demonstrated preserved cell viability at the working concentration (100 pM), supporting a non-cytotoxic and specific gene-silencing effect. These findings highlight PD-L1 as a viable molecular target and support siRNA-mediated silencing as a promising therapeutic strategy in TNBC. Full article

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23 pages, 1817 KB

Open AccessArticle

Formulation Optimization of Felodipine Push–Pull Osmotic Pump Capsules Using Quality by Design Approach

by Chaowalit Monton and Poj Kulvanich

Sci. Pharm. 2026, 94(3), 52; https://doi.org/10.3390/scipharm94030052 - 25 Jun 2026

Abstract

Recently, the Quality by Design (QbD) principle has been implemented in the pharmaceutical industry to enhance product and process understanding through a science- and risk-based approach. This study aimed to apply QbD principles to the formulation development of felodipine push–pull osmotic pump (PPOP) [...] Read more.

Recently, the Quality by Design (QbD) principle has been implemented in the pharmaceutical industry to enhance product and process understanding through a science- and risk-based approach. This study aimed to apply QbD principles to the formulation development of felodipine push–pull osmotic pump (PPOP) capsules. The quality target product profile (QTPP) and critical quality attributes (CQAs) were established. A Box–Behnken experimental design was employed to optimize the formulation variables, including the amounts of Polyox WSR N80, Polyox WSR Coagulant, and sodium chloride, selected based on the initial risk assessment. Four responses were monitored: lag time, release rate and R² based on zero-order release kinetics, and drug release at 24 h. Results indicated that the optimal formulation consisted of 125 mg Polyox WSR N80, 26 mg Polyox WSR Coagulant, and 30 mg sodium chloride. This formulation met the predefined criteria for lag time (≤6 h) and release kinetics (R² ≥ 0.95), while drug release at 24 h remained below the target value (≥80%). Because most fitted response surface models were not statistically significant, the generated regression equations and response surfaces were interpreted qualitatively to identify formulation trends rather than as predictive models. Experimental verification showed reasonable consistency in overall response trends, although substantial deviations between predicted and observed values were observed for some responses, particularly drug release at 24 h. Therefore, the present work should be considered a formulation-development and QbD feasibility study rather than a definitive optimization study. These findings demonstrate that the QbD-based approach enabled systematic, multivariate optimization and design space establishment, providing a more structured framework for formulation refinement compared with prior exploratory development and supporting controlled drug release characteristics of felodipine PPOP capsules. Full article

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20 pages, 1716 KB

Open AccessReview

Flavonoids in Cancer Therapy: Nanocarrier Strategies to Overcome Bioavailability Limitations

by Maykon Jhuly Martins de Paiva, Walmirton Bezerra D’Alessandro, Iangla Araújo de Melo Damasceno, Juliane Farinelli Panontin, Taides Tavares dos Santos, Sávia Denise Silva Carlotto Herrera, Mateus Silva Santos and Márcio Trevisan

Sci. Pharm. 2026, 94(2), 51; https://doi.org/10.3390/scipharm94020051 - 19 Jun 2026

Abstract

Flavonoids are a structurally diverse class of plant-derived polyphenolic compounds widely recognized for their pleiotropic biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In oncology, these compounds have demonstrated the ability to modulate key signaling pathways involved in cell proliferation, apoptosis, angiogenesis, and [...] Read more.

Flavonoids are a structurally diverse class of plant-derived polyphenolic compounds widely recognized for their pleiotropic biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In oncology, these compounds have demonstrated the ability to modulate key signaling pathways involved in cell proliferation, apoptosis, angiogenesis, and metastasis, highlighting their potential as multitarget therapeutic agents. However, their clinical translation remains significantly limited by unfavorable pharmacokinetic properties, such as poor aqueous solubility, extensive first-pass metabolism, rapid systemic clearance, and consequently low oral bioavailability. In this context, nanotechnology has emerged as a promising strategy to overcome these limitations. This review provides a comprehensive and critical analysis of current nanocarrier-based delivery systems for flavonoids, including polymeric nanoparticles, lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanoemulsions), micelles, and cyclodextrin complexes, emphasizing their role in improving drug stability, enhancing cellular uptake, and enabling targeted delivery to tumor tissues through both passive mechanisms, such as the enhanced permeability and retention effect, and active targeting approaches. In addition, recent in vitro and in vivo studies demonstrating the superior antitumor efficacy of nanoencapsulated flavonoids compared to free compounds are discussed. Finally, the major translational challenges, safety considerations, and future perspectives for the clinical application of flavonoid-based nanomedicines in cancer therapy are highlighted. Full article

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

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19 pages, 2203 KB

Open AccessArticle

Absolute Bioavailability and PK/PD of Quercetin in Normoglycemic and Alloxan-Induced Diabetic Rats

by Avel González-Sánchez, Jesús Alfredo Araujo-León, Rolffy Ortiz-Andrade, Tania Isolina Coral-Martínez and Zhelmy Martín-Quintal

Sci. Pharm. 2026, 94(2), 50; https://doi.org/10.3390/scipharm94020050 - 15 Jun 2026

Abstract

This study aimed to determine the absolute bioavailability of quercetin and quantitatively evaluate its pharmacokinetic–pharmacodynamic (PK-PD) relationship regarding acute glucose-lowering effects in normoglycemic and alloxan-induced diabetic rats, addressing whether its in vivo efficacy is driven by the free aglycone or its biotransformed intermediates. [...] Read more.

This study aimed to determine the absolute bioavailability of quercetin and quantitatively evaluate its pharmacokinetic–pharmacodynamic (PK-PD) relationship regarding acute glucose-lowering effects in normoglycemic and alloxan-induced diabetic rats, addressing whether its in vivo efficacy is driven by the free aglycone or its biotransformed intermediates. Healthy and diabetic rats received single doses of quercetin either orally (75 mg/kg) or intravenously (38 mg/kg). Plasma concentrations of free quercetin were quantified using a validated HPLC-DAD method, and temporal PK-PD relationships between systemic exposure and the percentage variation of glycemia were mathematically evaluated employing Pearson correlation analysis. The absolute bioavailability of free quercetin was significantly impaired by the pathophysiological state, dropping from 59.7% in healthy rats to 40.9% in diabetic subjects. Despite this diminished systemic exposure, oral administration elicited significant hypoglycemic responses. Crucially, the Pearson correlation analysis revealed a pronounced temporal dissociation: the onset of glycemic reduction occurred independently of the maximal circulating concentration of free quercetin. Furthermore, intravenous delivery bypassed first-pass barriers and induced a markedly faster and deeper hypoglycemic effect (up to −47% in diabetic rats). Finally, the diminished bioavailability under diabetic conditions and the stark PK-PD temporal dissociation strongly suggest that quercetin’s acute antihyperglycemic effect is driven by rapid hepatic Phase II biotransformation, implicating conjugated metabolites (rather than the free aglycone) as the principal pharmacological effectors. Full article

(This article belongs to the Topic Natural Products and Drug Discovery—2nd Edition)

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16 pages, 3738 KB

Open AccessArticle

Microwave-Assisted Synthesis and Characterization of Flavone–Thiazole–Aryl Hybrids with Potential Anticancer and Antiparasitic Activity

by Stepan Sysak, Wojciech Szczolko, Marziyeh Raeispour, Malgorzata Kucinska, Pawel Bakun, Roman Lesyk, Philippe Grellier, Marek Murias and Tomasz Goslinski

Sci. Pharm. 2026, 94(2), 49; https://doi.org/10.3390/scipharm94020049 - 10 Jun 2026

Abstract

Flavone–thiazole–aryl hybrid molecules based on 6-aminoflavone and 5-arylidene-4-aminothiazol-2(5H)-ones were synthesized and subjected to physicochemical and biological studies. Microwave-assisted synthesis was performed in two steps. First, an aminolysis reaction of isorhodanine with 6-aminoflavone was carried out to achieve the corresponding hybrid flavone-thiazole [...] Read more.

Flavone–thiazole–aryl hybrid molecules based on 6-aminoflavone and 5-arylidene-4-aminothiazol-2(5H)-ones were synthesized and subjected to physicochemical and biological studies. Microwave-assisted synthesis was performed in two steps. First, an aminolysis reaction of isorhodanine with 6-aminoflavone was carried out to achieve the corresponding hybrid flavone-thiazole 3, which was later subjected to a Knoevenagel condensation with selected aromatic aldehydes, yielding 5-arylidene derivatives 5a–5i. The resulting hybrids were purified and characterized by UV–Vis, NMR, and HR-MS (ESI). In the UV–Vis spectra of all compounds, two characteristic bands were noted. The UV–Vis spectra in DMF of the studied flavone–thiazole–aryl hybrids consist of two major bands with maxima appearing at 280–288 nm, corresponding to band II and 383–399 nm, corresponding to band I, which clearly distinguish them from the large group of modified flavonoids. Among the compounds tested on human bladder cancer 5637 cells, (5Z)-5-[(4-hydroxyphenyl)methylene]-4-[(4-oxo-2-phenyl-chromen-6-yl)amino]thiazol-2-one (5b) exhibited interesting micromolar activity (IC₅₀ 2.37 µM). In addition, four of the tested compounds (3, 5f, 5d, and 5b) presented noteworthy antiplasmodial activity against P. falciparum in the low micromolar range (IC₅₀ 1.90–4.90 µM). The obtained group of flavone–thiazole–aryl hybrid molecules constitutes valuable starting points for further structural optimisation, which could usher in future novel active pharmaceutical ingredients and pave the way for novel therapeutic strategies. Full article

(This article belongs to the Special Issue Heterocyclic Chemistry in Drug Design 3.0)

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29 pages, 768 KB

Open AccessArticle

2,4-Bis{4-[(dialkylaminoalkyl)aminomethyl]phenyl}-7-substituted-7H-pyrrolo[2,3-d]pyrimidine Derivatives: Synthesis and Biological Evaluation as Novel Antiprotozoal Agents by Potentially Targeting G-Quadruplex

by Jean Guillon, Solène Savrimoutou, Patrice Agnamey, Vittoria Milano, Céline Damiani, Luisa Ronga, Marie Hanot, Sandra Albenque, Tshering Zangmo, Sarah Monic, Noël Pinaud, Lindita Lari, Mathieu Marchivie, Stéphane Moreau, Jean-Louis Mergny, Serge Moukha, Pascale Dozolme, Clotilde Boudot, Bertrand Courtioux, Anita Cohen and Pascal Sonnet Show full author list Hide full author list

Sci. Pharm. 2026, 94(2), 48; https://doi.org/10.3390/scipharm94020048 - 9 Jun 2026

Abstract

A series of substituted pyrrolo[2,3-d]pyrimidines was designed, synthesized, and evaluated in vitro against two protozoan parasites: Plasmodium falciparum and Trypanosoma brucei brucei. Pharmacological studies revealed antiprotozoal activity with IC₅₀ values in the submicromolar to micromolar range. Additionally, the in [...] Read more.

A series of substituted pyrrolo[2,3-d]pyrimidines was designed, synthesized, and evaluated in vitro against two protozoan parasites: Plasmodium falciparum and Trypanosoma brucei brucei. Pharmacological studies revealed antiprotozoal activity with IC₅₀ values in the submicromolar to micromolar range. Additionally, the in vitro cytotoxicity of these new compounds was assessed using human HepG2 cells. Among them, the pyrrolopyrimidine derivative 1d emerged as the most potent antimalarial compound, exhibiting a selectivity index (SI) of 600.81 against the P. falciparum chloroquine-resistant W2 strain. For the chloroquine-sensitive 3D7 strain, the most notable selectivity index (SI) was observed for pyrrolo[2,3-d]pyrimidine 1c, with a value of approximately 123. Furthermore, compound 1b demonstrated the most interesting activity against Trypanosoma brucei brucei, with an SI of 39.52, marking it as a promising trypanocidal agent. FRET melting assays confirmed that these nitrogen-containing heterocyclic compounds bind to telomeric G-quadruplexes in P. falciparum and Trypanosoma. However, no clear correlation was found between G-quadruplex binding and antiparasitic activity or selectivity, suggesting that G-quadruplex targeting is unlikely to be the main mechanism underlying cytotoxicity. Full article

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

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14 pages, 4629 KB

Open AccessArticle

Evaluation of Plantago lanceolata (Ribwort Plantain) and StrepCough Plantain-Dry Cough Syrup in In Vitro Models of Pharyngitis and Cough

by Olumayokun A. Olajide, Uzeme P. Aluta, Emmanuel Mfotie Njoya, Hope A. Ogiogio and Thomas Hallett

Sci. Pharm. 2026, 94(2), 47; https://doi.org/10.3390/scipharm94020047 - 9 Jun 2026

Abstract

Symptoms of respiratory tract infections (RTI) caused by viral or bacterial triggers include sore throat and cough. Plantago lanceolata (ribwort plantain) is used in herbal medicine to treat symptoms of RTI. This study evaluated the pharmacological actions of P. lanceolata extract (PL) and [...] Read more.

Symptoms of respiratory tract infections (RTI) caused by viral or bacterial triggers include sore throat and cough. Plantago lanceolata (ribwort plantain) is used in herbal medicine to treat symptoms of RTI. This study evaluated the pharmacological actions of P. lanceolata extract (PL) and StrepCough Plantain-Dry cough syrup (PLS) in in vitro models of sore throat and cough. Human tonsil epithelial cells (HTEpiC) cells were stimulated with a combination of lipoteichoic acid and peptidoglycan in the presence or absence of PL or PLS. Levels of TNF-α, IL-6, PGE₂, and COX-2 were measured using ELISA, while phospho-p65 protein levels were measured using Lumit^® immunoassay. The effects of PL and PLS on bradykinin-induced inflammation and increased intracellular Ca²⁺ were investigated in bronchial epithelial cells (BEAS-2B), cells over-expressing TRPV1. Results showed that the pre-treatment of HTEpiC cells with PL and PLS resulted in a significant (p < 0.05) reduction in the LTA + PGN-induced increased production of TNFα, IL-6, PGE₂, as well as COX-2 and phospho-p65 protein levels. Bradykinin-induced increased levels of TNFα, IL-6, and PGE₂ in BEAS-2B cells over-expressing TRPV1 were also reduced by PL and PLS, while reducing levels of intracellular Ca²⁺. This study has demonstrated that extract of P. lanceolata and StrepCough Plantain-Dry cough syrup reduce inflammation in human tonsil epithelial cells. The extract and syrup also reduced TRPV1-mediated inflammation and increased intracellular Ca²⁺ in BEAS-2B bronchial epithelial cells. This study has provided pharmacological evidence for the use of P. lanceolata in healthcare interventions to treat symptoms of respiratory tract infection. Full article

(This article belongs to the Topic Natural Products and Drug Discovery—2nd Edition)

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19 pages, 21308 KB

Open AccessArticle

Ocular Irritation Potential and Cytotoxicity of Selected Surfactants and Cosurfactants: Identifying Suitable Concentrations for Topical Ophthalmic Formulations

by Zinah K. Al-Qaysi, Ali A. Al-Kinani and Raid G. Alany

Sci. Pharm. 2026, 94(2), 46; https://doi.org/10.3390/scipharm94020046 - 5 Jun 2026

Abstract

The cornea and conjunctiva are particularly susceptible to injury and adverse effects, either induced by topically applied drugs or excipients used in ophthalmic formulations. Surfactants and cosurfactants are important for producing topical eye formulations of poorly water-soluble drugs, yet they have not been [...] Read more.

The cornea and conjunctiva are particularly susceptible to injury and adverse effects, either induced by topically applied drugs or excipients used in ophthalmic formulations. Surfactants and cosurfactants are important for producing topical eye formulations of poorly water-soluble drugs, yet they have not been always used in concentrations that are nontoxic and non-irritating to the ocular surface. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. The ocular irritation of Tween 80, Cremophor EL, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) was examined using the HET-CAM (conjunctival) and BCOP (corneal) eye assays. The toxic effect of the four excipients after 24 h on HLE-B3 cell growth was investigated and found to be dose-dependent. The highest tolerable concentrations of Tween 80 and Cremophor EL were 0.25% (w/w), whereas PEG 400 and PG were non-toxic at 5% (w/w). Tween 80 and Cremophor EL at 0.25% (w/w) and PEG 400 and PG at 5% (w/w) were all devoid of conjunctival and corneal irritation. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. Interestingly, there is strong agreement between the results obtained using the HET-CAM and BCOP assays, where both have been successfully used to evaluate the potential for ocular irritation caused by the aforementioned excipients. Full article

(This article belongs to the Special Issue Innovative Perspectives in Ocular Drug Research)

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16 pages, 6578 KB

Open AccessArticle

Preparation, Kinetic Stability, and Dissolution Study of Amorphous Norfloxacin

by Alexander Gerasimov, Dar’ya Khabibulina, Liana Zubaidullina, Elina Mirgazieva, Nikolay Lyadov, Ruslan Nagrimanov and Semen Lapuk

Sci. Pharm. 2026, 94(2), 45; https://doi.org/10.3390/scipharm94020045 - 2 Jun 2026

Abstract

Obtaining amorphous forms of drugs is one of the ways to increase bioavailability. This is especially important for active pharmaceutical ingredients belonging to class II and IV according to the biopharmaceutical classification. These compounds include the currently widely used fluoroquinolone antibiotics. They have [...] Read more.

Obtaining amorphous forms of drugs is one of the ways to increase bioavailability. This is especially important for active pharmaceutical ingredients belonging to class II and IV according to the biopharmaceutical classification. These compounds include the currently widely used fluoroquinolone antibiotics. They have low solubility in water and are therefore typically used as hydrochlorides. The presence of a strong acid and a charged active pharmaceutical ingredient in the drug increases solubility, but can also lead to additional side effects and decreased permeability. One way to improve the properties of active pharmaceutical ingredients is to convert them to amorphous form. In this study, an amorphous form of the fluoroquinolone antibiotic norfloxacin was obtained, its stability was determined, and its solubility was studied. It was shown that the resulting amorphous form has good temporal stability. The optimal models describing the cold crystallization process are the Nakamura and Sbirrazzuoli models. Despite the slower dissolution kinetics compared to the crystalline sample, the amorphous form shows higher equilibrium solubility values. These results can be used in pharmaceutical engineering to produce amorphous forms of active pharmaceutical ingredients and determine their stability. Full article

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20 pages, 3907 KB

Open AccessArticle

Green-Synthesized Silver Nanoparticles Derived from Calotropis procera as a Multifunctional Nanotherapeutic Platform Targeting Helicobacter pylori, Oxidative Stress, Inflammation, and Gastric Cancer

by Mounishwaran Kamalesan, Mohanraj Raja, Rameshkumar Neelamegam, Muthukalingan Krishnan, Kayalvizhi Nagarajan and Douglas J. H. Shyu

Sci. Pharm. 2026, 94(2), 44; https://doi.org/10.3390/scipharm94020044 - 29 May 2026

Abstract

Green synthesis of silver nanoparticles (CP-AgNPs) using Calotropis procera (CP) offers a sustainable approach to producing multifunctional therapeutic nanomaterials. This study aimed to synthesize CP-AgNPs and evaluate their antimicrobial, antioxidant, anti-inflammatory, and anticancer potential, with a focus on Helicobacter pylori and gastric cancer [...] Read more.

Green synthesis of silver nanoparticles (CP-AgNPs) using Calotropis procera (CP) offers a sustainable approach to producing multifunctional therapeutic nanomaterials. This study aimed to synthesize CP-AgNPs and evaluate their antimicrobial, antioxidant, anti-inflammatory, and anticancer potential, with a focus on Helicobacter pylori and gastric cancer cells. CP-AgNPs were prepared by phytochemical reduction using CP leaf extract and characterized by UV–Vis, XRD, FTIR, SEM, EDX, TEM, and Zeta. Antibacterial activity against H. pylori, time-kill kinetics, and SEM imaging of membrane damage were performed. Antioxidant (DPPH, ABTS) and anti-inflammatory assays, together with cytotoxicity studies in AGS cells (DAPI, AO/EtBr, and SEM), were also conducted. CP-AgNPs exhibited an SPR peak at 432 nm, face-centered cubic crystallinity, and spherical morphology (8–32 nm). They showed strong, dose-dependent antibacterial activity against H. pylori, surpassing metronidazole at higher doses. Time-kill assays and SEM confirmed membrane disruption. Antioxidant activity was notable (IC₅₀: 40 µg/mL for DPPH; 60 µg/mL for ABTS). CP-AgNPs demonstrated significant anti-inflammatory effects and dose-dependent cytotoxicity in AGS cells, inducing apoptosis and morphological alterations. The broad biological activity of CP-AgNPs likely arises from the synergy between silver ions and CP phytochemicals. Their superior antibacterial effects, combined with antioxidant and anti-inflammatory properties, indicate strong therapeutic potential for gastric diseases. Anticancer activity in AGS cells suggests additional biomedical relevance, which may involve ROS-associated and apoptosis-related pathways, as suggested by previous studies. CP-AgNPs represent a promising natural nanoplatform for managing H. pylori infection, oxidative stress, inflammation, and gastric cancer, warranting further mechanistic and in vivo studies. Full article

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29 pages, 8385 KB

Open AccessArticle

Discovery of Potential Antihypertensive Agents from the Marine Microalga Phaeodactylum tricornutum Through Metabolite Profiling and In Silico Analysis

by Miguel Ernesto Guzmán-Rodríguez, Marco Antonio Valdez-Flores, Cinthia Ayón-Fernandez, José Juan Ordaz-Ortiz, Alma Marlene Guadrón-Llanos, Javier Magaña-Gómez, Alberto Kousuke de la Herrán-Arita, Josué Camberos-Barraza, Verónica Judith Picos-Cárdenas, Juan Fidel Osuna-Ramos, Claudia Desireé Norzagaray-Valenzuela and Loranda Calderón-Zamora

Sci. Pharm. 2026, 94(2), 43; https://doi.org/10.3390/scipharm94020043 - 21 May 2026

Abstract

Hypertension remains a leading cause of global morbidity and mortality, and angiotensin-converting enzyme (ACE) represents a central therapeutic target within the renin–angiotensin–aldosterone system. Marine microalgae, particularly Phaeodactylum tricornutum, provide an underexplored reservoir of structurally diverse metabolites with potential cardiovascular relevance. In this [...] Read more.

Hypertension remains a leading cause of global morbidity and mortality, and angiotensin-converting enzyme (ACE) represents a central therapeutic target within the renin–angiotensin–aldosterone system. Marine microalgae, particularly Phaeodactylum tricornutum, provide an underexplored reservoir of structurally diverse metabolites with potential cardiovascular relevance. In this in silico study, we characterized metabolites putatively annotated by UPLC-ESI-HRMS and evaluated their predicted ACE inhibitory potential. We performed molecular docking with AutoDock 4 and assessed pharmacokinetic and toxicological properties using the SwissADME, PASS, and ProTox platforms. Several metabolites showed favorable binding orientations within the ACE catalytic pocket, including interactions with key residues and proximity to the zinc-binding motif. Lehualide G, Val–Asn–Pro, tanariflavanone B, hydroxyterbinafine, and anhydro-vitamin A exhibited the most favorable docking profiles. PASS predictions indicated vascular-related bioactivity signals for selected compounds, whereas ADMET modeling revealed heterogeneous but classifiable pharmacokinetic and safety characteristics. The convergence of predicted binding compatibility, bioactivity signals, and stratified safety margins supports P. tricornutum as a promising source of candidate molecules for further experimental validation in antihypertensive research. Full article

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