Journal of Pharmaceutical Research International

Computer-Aided Design of Imidazo [4.5-c] Pyridin-4-one Derivatives as Antagonists of the Angiotensin II Type 1 (AT1) Receptor

Abel Landry Tebily — 2026-05-04

Over the past decade, drug resistance has emerged as a major challenge in the treatment of high blood pressure. This report evaluates new imidazo[4.5-c]pyridin-4-one compounds designed to inhibit the AT1 enzyme, and highlights their therapeutic potential, supported by favourable pharmacological properties. Three-dimensional (3D) models of AT1-IPx complexes were constructed via in situ modifications of the crystal structure of AT1-IP1 (PDB entry code: 4HEE), which acted as the reference compound for a training set of 15 and a validation set of 4 VIPs with established experimental inhibitory potencies IC₅₀^exp. To ascertain the active conformation of IP1-15, we devised a gas-phase quantitative structure-activity relationship (QSAR) model that established a linear correlation between the computed free energies (ΔΔG_com) of AT1-IP complex formation and the experimentally derived pIC₅₀^exp values, where pIC₅₀^exp= − logIC₅₀^exp. Subsequently, we evaluated the Virtual Compound Library (VCL) utilizing Lipinski's Rule of Five and the PH4 model, followed by an assessment of the potency of the novel IP analogues employing the maintained QSAR model. The pharmacokinetic characteristics of the resultant analogues have been assessed. The linear correlation equation obtained for the QSAR model is: pIC₅₀^exp= − 0.0687×ΔΔG_com + 8.035 (R² = 0.94). This relationship shows a strong correlation between the calculated free energies (ΔΔGcom) and the experimental values of pIC₅₀. Additionally, the linear correlation between experimental and predicted values for the pharmacophoric model (PH4) is expressed as follows: pIC₅₀^exp= 0.9316 × pIC₅₀^pre+ 0.497 (R² = 0.93). This correlation validates the good predictive power of the developed pharmacophoric model. Lastly, the virtual screening of the IP analogue library found 43 compounds that might work well when taken by oral or through intravenous applications. The best candidate among them had a good pharmacokinetic profile and a preliminary inhibitory power (IC₅₀^pre) of 29.18 pm which was linked to a positive pharmacokinetic profile. This makes it a promising candidate for future experimental studies. The combination of molecular modelling and pharmacophore-based screening of the virtual library has led to the identification of new antihypertensive agents with favourable pharmacokinetic profiles.

Unveiling the Therapeutic Potential: Cylicodiscus gabunensis (FABACEAE) Aqueous Stem Bark Extract Derived Silver Nanoparticles for Enhanced Anti-inflammation in Wistar Rats

Francois Eya’ane Meva — 2026-05-13

Background: Medicinal plants and green-synthesized silver nanoparticles have gained increasing attention as potential alternatives to conventional anti-inflammatory therapies due to their bioactivity, biocompatibility, and reduced toxicity.

Aims: The present study investigates the anti-inflammatory activity of silver nanoparticles (AgNPs) biosynthesized using the aqueous stem bark extract of Cylicodiscus gabunensis. The aqueous extract was prepared by infusion and reacted with silver nitrate to generate AgNPs.

Study Design: Experimental.

Place and Duration of Study: Department pharmaceutical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Cameroon, between November 2021 and June 2022.

Methodology: Comprehensive physicochemical characterization was carried out using UV-Vis spectrophotometry to confirm nanoparticle formation, Fourier-transform infrared spectroscopy (FTIR) to identify functional groups at the metal-biomolecule interface, powder X-ray diffraction (XRD) to assess crystallinity and purity, scanning electron microscopy (SEM) to examine morphology, and energy-dispersive X-ray spectroscopy (EDX) to determine elemental composition.Acute toxicity was evaluated in accordance with OECD Guideline 425, while anti-inflammatory activity was assessed in vitro using the bovine serum albumin (BSA) denaturation assay and in vivo using the carrageenan-induced rat paw edema model.

Results: The synthesized AgNPs were stable, crystalline, composed of elemental silver, and no signs of acute toxicity were observed. Notably, the AgNPs exhibited pronounced anti-inflammatory activity, achieving 95% inhibition of BSA denaturation at 200 µg/mL in vitro and 91% inhibition of paw edema at 400 µg/kg in vivo.

Conclusion: Overall, silver nanoparticles biosynthesized from Cylicodiscus gabunensis stem bark demonstrated potent anti-inflammatory effects coupled with low toxicity, highlighting their promise as a plant-derived, biocompatible alternative for the management of inflammatory disorders.

Evaluation of the Nootropic Activity of the Ethanolic Leaf Extract of Couroupita guianensis in Scopolamine Induced Amnesia Models

Srinivasu Matta — 2026-05-18

Background: Alzheimer’s disease and related cognitive disorders are characterized by progressive impairment of learning and memory, often associated with cholinergic dysfunction. Natural plant-derived compounds are being explored as potential nootropic agents with neuroprotective properties. Therefore, this study was undertaken to evaluate the nootropic potential of the ethanolic leaf extract of Couroupita guianensis (ELECG) in mice.

Methods: The nootropic activity of ELECG was assessed at selected dose levels using established behavioral models of learning and memory. Donepezil was used as the standard reference drug, while Scopolamine (1 mg/kg, i.p.) was administered to induce experimental amnesia. Cognitive performance was evaluated using the Elevated Plus Maze, Radial Arm Maze, and Y-maze paradigms in scopolamine-induced amnesic mice. Brain acetylcholinesterase (AChE) activity was estimated in whole-brain homogenates to assess cholinergic function.

Results: Treatment with ELECG significantly improved behavioral performance and increased spontaneous alternation behavior in the Y-maze test from 20.83 ± 3.81% in the disease control group to 71.14 ± 14.49% (p < 0.01) and 77.38 ± 11.42% (*p < 0.001) at 400 mg/kg, indicating enhancement of spatial working memory. In the Elevated Plus Maze model, ELECG significantly reduced transfer latency and memory errors in scopolamine-treated mice, with working memory errors decreasing from 4.9 ± 0.52 in the disease control group to 1.6 ± 0.24 (p < 0.01) at 400 mg/kg, suggesting improved learning and memory retention. The extract also enhanced locomotor activity and markedly reduced brain AChE activity from 3.03 ± 0.11 in the disease control group to 2.20 ± 0.12 (p < 0.01) at 400 mg/kg, comparable to donepezil treatment (1.95 ± 0.08; p < 0.01), indicating restoration of cholinergic neurotransmission disrupted by scopolamine.

Conclusion: These findings demonstrate that ELECG enhances learning and memory across multiple experimental paradigms. The reduction in brain AChE activity further supports its neuroprotective and cognition-enhancing effects. Therefore, the leaf extract of Couroupita guianensis may represent a promising therapeutic candidate for the management of Alzheimer’s disease and related cognitive disorders.

Postbiotic and Phytochemical Modulation of Multispecies Periodontal Biofilms: Comparative Effects on Biofilm Viability and Porphyromonas Gingivalis Virulence

Mehmet Murat TASKAN — 2026-05-21

Background: Periodontal diseases are associated with complex multispecies biofilms in which Porphyromonas gingivalis acts as a key virulence-associated pathogen contributing to inflammation and tissue destruction. Owing to the limitations of conventional antimicrobials, postbiotics and phytochemicals are emerging as promising alternative strategies for reducing biofilm viability and attenuating bacterial virulence.

Purpose: To compare the antibiofilm and antivirulence effects of 0.12% chlorhexidine, Lactobacillus reuteri cell-free supernatant, green tea extract, and their combination against a multispecies periodontal biofilm model.

Materials and Methods: Artificial saliva-conditioned hydroxyapatite discs were used to establish a sequential multispecies biofilm containing Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis. Biofilms were allocated to five groups: untreated control, 0.12% chlorhexidine, L. reuteri cell-free supernatant, green tea extract, and combined L. reuteri cell-free supernatant plus green tea extract. Metabolic activity, total biomass, viable bacterial proportion, relative P. gingivalis load, and gingipain activity were quantified after standardized exposure. Data from three independent biological experiments with three technical replicates per condition were analyzed using one-way ANOVA and Tukey post hoc tests.

Results: All active treatments significantly reduced biofilm-related outcomes compared with the untreated control group (P<0.001). Chlorhexidine showed the strongest bactericidal profile, reducing metabolic activity to 24.60 +/- 4.90% and viable bacterial proportion to 28.50 +/- 5.20%. The combined postbiotic-phytochemical treatment showed broad inhibition, reducing total biomass to 42.50 +/- 6.90%, relative P. gingivalis load to 33.10 +/- 6.30%, and gingipain activity to 28.40 +/- 5.50%. Green tea extract showed a marked antivirulence-dominant effect on gingipain activity.

Conclusion: Chlorhexidine provided superior short-term bactericidal activity, whereas the combined postbiotic-phytochemical approach showed relevant multi-endpoint antibiofilm and antivirulence effects in this in vitro model. These findings support further mechanistic and translational evaluation of postbiotic-phytochemical adjuncts for periodontal biofilm modulation.

Exploring the Antifungal Effects of Lactiplantibacillus plantarum on Candida albicans: A review

Juel Mariam Mathew — 2026-05-21

Candida albicans is one of the major pathogens of concern as an opportunistic fungal organism that is a normal component of the human microbiota. Vulvo vaginal candidiasis is commonly seen in women and can impact up to 75% of women at least once during their lifetime. People with AIDS are prone to oral and esophageal candidiasis, and these infections frequently lead to oral cancers, denture use, and these patients do not have the ability to produce saliva. Individuals with burns and newborns especially premature babies are also vulnerable to C. albicans skin infections. In patients belonging to vulnerable groups and weak individuals in intensive care units, it may enter the bloodstream and cause infection called candidaemia, which will lead to disseminated candidiasis if the infection spreads to internal organs. Death rates reported in various studies ranging from 30–50%; some studies show that this is the second largest leading reason for death. As antifungal drug-resistant Candida infections are increasingly reported, alternative antifungal strategies are required. Lactiplantibacillus plantarum is one of the most versatile and extensively studied species due to its adaptability to diverse environmental conditions and its metabolic flexibility. L. plantarum is known to produce a wide range of antimicrobial compounds. The ability of L. plantarum to produce both bacteriocins and biosurfactants makes it a highly promising microorganism for the development of new antimicrobial strategies. As a fermentative bacterium, it shows strong potential for use in developing precision probiotics against Candida infections.

Rare Plant-Derived Polysaccharides as Next-Generation Drug Delivery Carriers: Opportunities, Challenges, and Future Perspectives

Antesh Kumar Jha — 2026-04-30

Rare plant-derived polysaccharides have emerged as promising biomaterials for advanced drug delivery due to their structural adaptability and functional performance. This review critically evaluates polysaccharides from underutilized sources such as tamarind seed, fenugreek, bael fruit, jackfruit, okra, aloe, and Plantago ovata. Tamarind polysaccharide-based systems demonstrate high encapsulation efficiency (>70%) and sustained drug release beyond 8–12 h with enhanced mucoadhesion and prolonged residence time. Thiolated fenugreek mucilage exhibits improved swelling and controlled release in gastroretentive formulations. Bael and jackfruit polysaccharides provide good mechanical strength and stability in matrix and nanocarrier systems. Okra-based formulations show high drug entrapment (>75%) and extended release, supporting colon-targeted delivery. Aloe polysaccharide hydrogels enable sustained release and improved tissue regeneration, while Plantago ovata allows enzyme-triggered site-specific drug release. Despite these advantages, variability, limited toxicity data, and scale-up challenges hinder clinical translation. Overall, these polysaccharides offer improved functional performance over conventional polymers and require further standardization for pharmaceutical applications.

Bovine Theileriosis: Epidemiology, Pathogenesis, Diagnosis, and Control Strategies

Taghreed H. Alwuthaynani — 2026-05-05

Bovine theileriosis is a significant tick-borne parasitic disease that poses a major threat to cattle health and productivity. This review summarizes current understanding of its etiology, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, and control with particular emphasis on Theileria annulata. The disease is transmitted by ixodid ticks and causes major severe economic losses due to reduced milk production, weight loss, increased mortality, and high treatment costs. Theileria pathogenesis is linked to the ability of the parasite to transform host leukocytes into proliferative cells, which promote disease progression and immunopathology. Clinical manifestations range from fever and anemia to lymphadenopathy and systemic complications. Diagnosis relies on a combination of clinical observation, microscopic examination, serological assays, and advanced molecular techniques, with PCR-based and CRISPR-based methods offering high sensitivity and specificity. Theileriosis control remains challenging due to drug resistance, limited vaccine efficacy, and the persistence of carrier animals. This review emphasizes the importance of developing integrated disease management, studying the host genetic resistance, and providing advanced molecular research for the development of effective vaccines and sustainable control strategies against bovine theileriosis.

Computer-Aided Drug Design Approaches for Benzilic Acid and Benzilate Derivatives: From Muscarinic Antagonists to Scaffold-Centred Workflows

Sipra Sarkar Banerjee — 2026-05-13

Benzilic acid (2-hydroxy-2,2-diphenylacetic acid) and its derivatives occupy a distinctive niche in medicinal chemistry because the scaffold naturally combines (i) a bulky, “aryl-rich” hydrophobic domain and (ii) a polar, acid/ester-bearing handle that can be tuned for permeability, residence time, and receptor selectivity. These attributes underpin clinically important antimuscarinic drugs and tool ligands whose binding modes have been structurally resolved, enabling genuinely structure-guided optimisation. In parallel, modern computer-aided drug design (CADD) has matured from “docking-first” workflows to integrated pipelines that explicitly manage protonation/tautomeric uncertainty, conformational flexibility, induced fit, binding kinetics, and developability constraints. This review synthesiseshow contemporary CADD can be applied to benzilic acid derivatives, with emphasis on (a) structure-based design empowered by high-resolution muscarinic acetylcholine receptor structures co-crystallised with benzilate-type ligands and related antagonists, (b) ligand-based modelling that leverages scaffold-centric series and robust negative data, and (c) translation-oriented in silico profiling to triage liabilities early. A structured search was conducted in PubMed, Web of Science, Scopus, and Google Scholar (January 2010 - March 2025) using specific scaffold and computational method terms, including peer-reviewed English articles involving benzilic acid derivatives and explicit CADD components.We outline a concise and reproducible literature-selection strategy, map the chemical and biological design space of benzilic acid derivatives, and present case-study patterns illustrating what has worked (and why) in achieving subtype selectivity and longer duration of action. Finally, we propose practical, reportable best practices—particularly around stereochemistry, protonation states, and benchmarking—that can raise confidence in CADD conclusions for this scaffold class and accelerate the design–make–test–analysecycle.