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Discovery of Arylfuran and Carbohydrate Derivatives from the BraCoLi Library as Potential Zika Virus NS3pro Inhibitors
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Water-Soluble Cu(II) Complexes with Polypyridyl Ligands: Anticancer Activity and DNA Interaction
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Effects of Sinensetin, Eupatilin, and Jaceosidin on Human Melanogenesis: A Pilot Study
Journal Description
Future Pharmacology
Future Pharmacology
is an international, peer-reviewed, open access journal on pharmacology, drug discovery, and therapeutics published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), EBSCO, and other databases.
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 19.2 days after submission; acceptance to publication is undertaken in 3.7 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
- Future Pharmacology is a companion journal of Pharmaceutics.
Latest Articles
Recovery from AMPA Receptor Potentiation by Ampakines
Future Pharmacol. 2025, 5(2), 27; https://doi.org/10.3390/futurepharmacol5020027 - 31 May 2025
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Background: Ampakines are a family of molecules that enhance the functioning of AMPA-glutamate receptors (AMPAR). High-impact ampakines completely offset receptor desensitization and enhance agonist binding affinity, while low-impact ampakines only modestly affect receptor desensitization and do not alter agonist binding affinity. Nonetheless, little
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Background: Ampakines are a family of molecules that enhance the functioning of AMPA-glutamate receptors (AMPAR). High-impact ampakines completely offset receptor desensitization and enhance agonist binding affinity, while low-impact ampakines only modestly affect receptor desensitization and do not alter agonist binding affinity. Nonetheless, little is known about AMPAR recovery following ampakine treatment. Methods: Herein, we study the effects of ampakines on AMPAR recovery and the interaction between high- and low-impact ampakines. Results: The high-impact ampakine CX729 did not induce any current in the absence of glutamate, but it dramatically increased glutamate-induced steady-state inward currents. Recoveries from the enhancement were significantly slower than those for the low-impact ampakine CX516, as was also seen on miniature synaptic currents. Electrophysiological interaction studies suggest that high- and low-impact ampakines may have different binding sites. We further investigated the induction of the potentiated response by measuring glutamate-induced responses after transient applications of CX729 or CX729 plus glutamate. Under both circumstances, subsequent application of glutamate yielded comparably potentiated responses. Furthermore, the recovery time was not different if saline was substituted for glutamate during the recovery period. Conclusions: These observations show that AMPAR potentiation by CX729 does not require the simultaneous presence of glutamate, nor is the slow reversal of the effects of the ampakine altered by subsequent receptor activation. Hence, the slow recovery from the effects of these select ampakines on the AMPAR may be the result of slow dissociation kinetics. We posit that the slow recovery of AMPAR from high-impact ampakines may contribute to the seizurogenic effects of this drug class and that high-impact ampakines that allow for more rapid AMPAR recovery may be safer and more clinically viable candidates.
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Open AccessArticle
Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs
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Bradley S. Wahle, Peter Pushko, Katie Albanese, Dylan M. Johnson, Irina Tretyakova, Igor S. Lukashevich and Thomas Rudge
Future Pharmacol. 2025, 5(2), 26; https://doi.org/10.3390/futurepharmacol5020026 - 31 May 2025
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(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice.
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(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice. A 2-week repeat dose toxicity study was performed in guinea pigs under Good Laboratory Practice (GLP) regulations to assess the local and systemic toxicological effects. (3) Results: Following an intramuscular (IM) or subcutaneous (SC) injection of 104 PFU of ML29-SF LASV vaccine at the start of the study, with a second dose 15 days later, no toxicological response attributable to the vaccine was observed. Vaccine-related effects were not observed in any in-life or post-mortem parameter evaluated, including clinical observations, injection site observations, body temperature, body weight, food consumption, ophthalmology, immunology, hematology, clinical chemistry, gross anatomical pathology, organ weights, and histopathology. An immunogenic response, as measured by the elicitation of IgG antibodies against major LASV immunogens, nucleocapsid and glycoprotein precursor, was observed in all vaccine-treated animals prior to the booster dose (Study Day 15) which endured through the end of the study (Study Day 42). There was no evidence of viral shedding in any vaccinated animal. (4) Conclusions: Overall, this single-dose vaccine was locally and systemically well tolerated even after a two-dose repeat administration, confirming the high level of safety of ML29-SF vaccination and supporting the future evaluation of this LASV vaccine, including in clinical trials.
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Open AccessArticle
KRM-II-81, a β3-Preferring GABAA Receptor Potentiator, Blocks Handling-Induced Seizures in Theiler’s Murine Encephalomyelitis Virus-Infected Mice
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Dishary Sharmin, Kamal P. Pandey, Lalit K. Golani, Sepideh Rezvanian, Md Yeunus Mian, Janet L. Fisher, Arnold Lippa, James M. Cook, Daniel P. Radin, Jodi L. Smith, Jeffrey M. Witkin, Hana Shafique and Rok Cerne
Future Pharmacol. 2025, 5(2), 25; https://doi.org/10.3390/futurepharmacol5020025 - 30 May 2025
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Background: The GABAA receptor (GABAAR) potentiator, KRM-II-81, is being developed as a novel antiseizure medication with reduced potential for sedation, tolerance development, and abuse liability. Although KRM-II-81 has been shown to provide antiseizure protection against a broad array of seizure induction paradigms,
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Background: The GABAA receptor (GABAAR) potentiator, KRM-II-81, is being developed as a novel antiseizure medication with reduced potential for sedation, tolerance development, and abuse liability. Although KRM-II-81 has been shown to provide antiseizure protection against a broad array of seizure induction paradigms, seizures induced by viral vectors have not been previously studied. GABAARs with specific α subunit compositions have been studied in relation to the reduced side-effect liability of KRM-II-81; however, the role of β subunit composition has yet to be determined. Methods: In the present study, KRM-II-81 was studied against handling-induced seizures in Theiler’s murine encephalomyelitis virus (TMEV)-infected mice. Results: An intracerebral infusion of TMEV on day 0 increased the cumulative seizure burden in mice when assessed for handling-induced seizures on days 3–7. KRM-II-81 (15 mg/kg, p.o., bid) nearly completely suppressed seizures in TMEV-infected mice over the course of daily treatments. The number of the most severe seizures (stage 5, tonic/clonic seizures) in the mice was suppressed to zero by KRM-II-81. Although the selectivity of KRM-II-81 for GABAAR α2/3 receptor subtypes might imbue KRM-II-81 with a reduced side-effect liability, other mechanisms are possible, and the potentiation of β1-containing GABAARs has been implicated in inducing sedation. The role of β subunit composition has yet to be determined for KRM-II-81. In electrophysiological studies with cells transfected with αxβ1γ2 or αxβ3γ2, KRM-II-81 preferentially potentiated GABA responses in cells containing β3 subunits in α2/3-containing GABAARs. Conclusions: The present findings confirm the robust antiseizure activity of KRM-II-81, now extended to a virus-induction model, and suggest a possible role of reduced β1-potentiation in the low side-effect profile of KRM-II-81.
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Open AccessReview
AI-Driven Chemical Design: Transforming the Sustainability of the Pharmaceutical Industry
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Antonio Ruiz-Gonzalez
Future Pharmacol. 2025, 5(2), 24; https://doi.org/10.3390/futurepharmacol5020024 - 29 May 2025
Abstract
The pharmaceutical industry faces mounting pressure to reduce its environmental impact while maintaining innovation in drug development. Artificial intelligence (AI) has emerged as a transformative tool across healthcare and drug discovery, yet its potential to drive sustainability by improving molecular design remains underexplored.
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The pharmaceutical industry faces mounting pressure to reduce its environmental impact while maintaining innovation in drug development. Artificial intelligence (AI) has emerged as a transformative tool across healthcare and drug discovery, yet its potential to drive sustainability by improving molecular design remains underexplored. This review critically examines the applications of AI in molecular design that can support in advancing greener pharmaceutical practices across the entire drug life cycle—from design and synthesis to waste management and solvent optimisation. We explore how AI-driven models are being used to personalise dosing, reduce pharmaceutical waste, and design biodegradable drugs with enhanced environmental compatibility. Significant advances have also been made in the predictive modelling of pharmacokinetics, drug–polymer interactions, and polymer biodegradability. AI’s role in the synthesis of active pharmaceutical compounds, including catalysts, enzymes, solvents, and synthesis pathways, is also examined. We highlight recent breakthroughs in protein engineering, biocatalyst stability, and heterogeneous catalyst screening using generative and language models. This review also explores opportunities and limitations in the field. Despite progress, several limitations constrain impact. Many AI models are trained on small or inconsistent datasets or rely on computationally intensive inputs that limit scalability. Moreover, a lack of standardised performance metrics and life cycle assessments prevents the robust evaluation of AI’s true environmental benefits. In particular, the environmental impact of AI-driven molecules and synthesis pathways remains poorly quantified due to limited data on emissions, waste, and energy usage at the compound level. Finally, a summary of challenges and future directions in the field is provided.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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Antimicrobial Activity of N-Methyl 4-Piperidone-Derived Monoketone Curcuminoids Against Cariogenic Bacteria
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Richard H. Lima, Yan R. Robles, Isabelle M. Oliva, Anna L. O. Santos, Júlia G. Teixeira, Maria A. S. C. Chellegatti, Niege A. J. C. Furtado, Carlos H. G. Martins, Viviani Nardini and Antônio E. M. Crotti
Future Pharmacol. 2025, 5(2), 23; https://doi.org/10.3390/futurepharmacol5020023 - 19 May 2025
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Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N
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Background/Objectives: Dental caries and candidiasis are major health problems worldwide. Dental caries is caused by cariogenic bacteria, especially those belonging to the Streptococcus genus, whereas candidiasis is caused by Candida species. In this study, the antimicrobial activity of a series of synthetic N-methyl-4-piperidone-derived monoketone curcuminoids (MKCs) against Candida albicans, C. krusei, and a representative panel of cariogenic bacteria was assessed. Methods: Fifteen MKCs were synthesized using an environmentally friendly base-catalyzed Claisen–Schmidt condensation between an aromatic aldehyde (R-PhCHO) and N-methyl-4-piperidone ethanol using NaOH as the catalyst. These compounds were evaluated for their antibacterial activity against a representative panel of cariogenic bacteria, along with their antifungal activity against Candida krusei and C. albicans. The antimicrobial activity was determined based on the Minimum Inhibitory Concentration (MIC) values. Results: Most of the compounds were obtained in about 2 h in yields ranging from 40 to 70%. None of the compounds displayed antifungal activity, even at 100 μg/mL, the highest tested concentration. Similarly, none of the compounds were active against Enterococcus faecalis. On the other hand, compounds 1 (R = H), 10 (R = 3,4,5-OMe), and 13 (R = 3-F) displayed moderate activity against Streptococcus mutans (13), S. salivarus (1), L. paracasei (1 and 10), S. mitis (1, 10, and 13), S. sanguinis (1, 10, and 13), and S. sobrinus (13), with MIC values of 250 μg/mL and 500 μg/mL. The presence of the N-methyl-4-piperidone ring was found to boost the antibacterial activity as compared to the corresponding acetone-derived MKCs. Moreover, the antibacterial activity of compounds 10 and 13 was associated with the presence and position of the fluor atom and the methoxy groups at the aromatic ring. Conclusions: This study contributed to a better understanding of the antimicrobial activity of MKCs, whose data in the literature are still scarce.
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Open AccessArticle
Effects of Polydatin on Pentylenetetrazol-Induced Seizures in Zebrafish Larvae
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Fernanda Barros de Miranda, Lucia Emanueli Schimith, Dennis Guilherme da Costa Silva, Camila de Oliveira Vian, Diele Bopsin da Luz, Rafael Felipe de Aguiar, Crístian Yan Montana da Rocha, Anna Maria Siebel, Jean Pierre Oses and Mariana Appel Hort
Future Pharmacol. 2025, 5(2), 22; https://doi.org/10.3390/futurepharmacol5020022 - 15 May 2025
Abstract
Background/Objectives: Epilepsy is a common neurological condition characterized by the occurrence of a seizure. It affects around 50 million individuals worldwide, and despite the large quantity of anti-seizure medications available, 30% of epileptic patients still suffer from seizures. Therefore, it is necessary to
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Background/Objectives: Epilepsy is a common neurological condition characterized by the occurrence of a seizure. It affects around 50 million individuals worldwide, and despite the large quantity of anti-seizure medications available, 30% of epileptic patients still suffer from seizures. Therefore, it is necessary to find new therapeutic options. Interestingly, polydatin has shown promising effects on epilepsy treatment due to its antioxidant and anti-inflammatory properties. Thus, this study aimed to evaluate the effects of polydatin (200, 300, and 400 µM) on a pentylenetetrazol (PTZ)-induced seizure model in wild-type zebrafish (Danio rerio) larvae. Methods: Seizure-like behavior, cell death, reactive species (RS) production, and lipid peroxidation were analyzed. Results: Pre-treatment with polydatin at 200 and 300 µM did not have a significant impact on seizure occurrence and the behavior of animals exposed to PTZ. Diazepam decreased seizure occurrence and increased the latency to achieve each seizure stage. Exposure to PTZ increased the swimming activity, and this effect was suppressed by diazepam but not by polydatin. PTZ exposure increased the RS production, which was significantly attenuated by polydatin at 400 µM and DMSO. Cell death and lipid peroxidation were not changed when compared to the experimental groups. Conclusions: Only the experimental positive control (diazepam) showed anti-seizure effects. Therefore, we failed to observe any anti-seizure effects of polydatin using a zebrafish experimental model. However, we cannot rule out its effects in other experimental models and different treatment protocols.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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Open AccessSystematic Review
Harnessing the Power of Natural Terpenoid Compounds Against Esophageal Squamous Cell Carcinoma: A Systematic Review
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Eugene Jamot Ndebia and Gabriel Tchuente Kamsu
Future Pharmacol. 2025, 5(2), 21; https://doi.org/10.3390/futurepharmacol5020021 - 6 May 2025
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Background/Objectives: Limitations of conventional treatments for esophageal cancer, which include poor solubility, drug resistance, and undesirable side effects, make it imperative to explore new therapeutic approaches to slow the progression of this disease. This study aims to assess the potential of terpene compounds
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Background/Objectives: Limitations of conventional treatments for esophageal cancer, which include poor solubility, drug resistance, and undesirable side effects, make it imperative to explore new therapeutic approaches to slow the progression of this disease. This study aims to assess the potential of terpene compounds as anti-cancer agents for esophageal squamous cell carcinoma (ESCC). Methods: This work was carried out following the PRISMA 2020 guidelines to ensure rigorous methodology. Results: A systematic analysis of 34 compounds revealed various mechanisms of action, such as induction of oxidative stress and modulation of apoptotic pathways. The results also show that several compounds, including (1Z,3R,4S,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene, dehydrocostus lactone, (3R,4S)-3,4,6,7-tetrachloro-3,7-dimethyl-octene-1-ene, acetyl-macrocalin B, jesridonin, longikaurin A, sphaerococcenol A, DS2, rabdocoestin B, ingenol C, ingenol-3,20-dibenzonate, JDA-202, xerophilusin B, betulinic acid, euphol, and (20S) ginsenoside Rh2, with IC50s below 10 µM, show promising efficacy both in vitro and in vivo, sometimes surpassing certain conventional treatments. Conclusions: However, despite these encouraging prospects, limitations remain, notably a lack of in vivo data and clearly defined mechanisms of action for certain compounds. These challenges require further research to validate their safety and efficacy, facilitating their development as viable therapeutic options for ESCC.
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Open AccessReview
Can Drug-Induced Yawning Serve as a Biomarker for Drug Safety and Effectiveness?
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Mohammad Rokan Ali, Khaled Alzaeem, Mostafa Bejermie, Cole Ngwachi Mangong Fofang, Siamand Mohamad and Parisa Gazerani
Future Pharmacol. 2025, 5(2), 20; https://doi.org/10.3390/futurepharmacol5020020 - 29 Apr 2025
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Background/Objectives: Yawning, a common physiological behavior, has emerged as a potential biomarker for drug responsiveness and side effects. This scoping review synthesizes current evidence on drug-induced yawning (DIY), focusing on its neurobiological mechanisms and clinical implications. Methods: A scoping review (INPLASY
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Background/Objectives: Yawning, a common physiological behavior, has emerged as a potential biomarker for drug responsiveness and side effects. This scoping review synthesizes current evidence on drug-induced yawning (DIY), focusing on its neurobiological mechanisms and clinical implications. Methods: A scoping review (INPLASY registration number: INPLASY202540048) was conducted using PubMed, Scopus, and Web of Science, including studies published in the past decade. The review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Handbook guidelines, ensuring systematic selection. Selected articles led to the analysis of 10 relevant studies encompassing 473 participants. Studies were evaluated for relevance to DIY, neurobiology, and clinical applications, with thematic analysis used to synthesize findings. Results: Four key themes emerged. (1) Yawning patterns: DIY involves frequent episodes (up to 80 yawns/day), varying by drug type and dosage. (2) Neurobiological mechanisms: Yawning is mediated by serotonin, dopamine, and oxytocin pathways, particularly via 5-HT2C and μ-opioid receptors. (3) Drug responsiveness: DIY is linked to SSRIs, opioids, and dopamine agonists. SSRIs induce yawning, while opioids suppress it, reflecting distinct neurochemical effects. (4) Clinical implications: Yawning may serve as a non-invasive biomarker for drug efficacy and side effects, particularly in opioid withdrawal and SSRI monitoring. Conclusions: DIY holds promise as a biomarker for drug safety and effectiveness, but research is limited by small sample sizes, methodological variability, and the absence of standardized yawning metrics. Future studies should establish consistent measures, account for interindividual variability, and evaluate DIY’s long-term clinical utility across diverse populations.
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Open AccessArticle
An In Vitro Diacetylcurcumin Study for Periodontitis: A New Approach to Controlling Subgingival Biofilms
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Valdo Antonio Aires da Silva, Bruno Bueno-Silva, Luciene Cristina Figueiredo, Tatiane Tiemi Macedo, Lucas Daylor Aguiar da Silva, Helio Chagas Chaves de Oliveira Junior, Carlos Roberto Polaquini, Luís Octávio Regasini and Janaina de Cássia Orlandi Sardi
Future Pharmacol. 2025, 5(2), 19; https://doi.org/10.3390/futurepharmacol5020019 - 25 Apr 2025
Abstract
Background: Periodontal disease (PD) is a chronic inflammatory condition associated with dysbiotic biofilm, leading to the destruction of bone and periodontal ligament. Scaling and root planing (SRP) is the gold-standard treatment for PD, but some patients may not respond adequately, necessitating adjunctive therapies.
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Background: Periodontal disease (PD) is a chronic inflammatory condition associated with dysbiotic biofilm, leading to the destruction of bone and periodontal ligament. Scaling and root planing (SRP) is the gold-standard treatment for PD, but some patients may not respond adequately, necessitating adjunctive therapies. This study investigated the antimicrobial activity of diacetylcurcumin (DAC), a modified curcumin, against multispecies subgingival biofilm associated with periodontitis. Methods: The biofilm, containing 40 bacterial species, was cultured for seven days in the Calgary apparatus. Treatments with DAC (200 μg/mL), 0.12% chlorhexidine (CHX), and a vehicle (control) were applied twice daily for 1 min, starting on the third day. On the seventh day, biofilms were analyzed for metabolic activity (MA) and bacterial counts via DNA-DNA hybridization. DAC toxicity was tested on Galleria mellonella larvae. Results: DAC reduced biofilm metabolic activity by 51%, while CHX achieved 88% reduction compared to the vehicle (p < 0.05). DAC also significantly decreased counts of key periodontal pathogens, including P. gingivalis, T. forsythia, P. intermedia, and A. actinomycetemcomitans (p < 0.05). At the tested concentration, DAC showed no toxicity in larvae. Conclusions: These findings suggest that DAC effectively reduces biofilm activity and periodontal pathogen counts, presenting a promising adjunctive therapy for PD.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2024)
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Open AccessReview
Scientifically Supported Best Practices in Leachable Screening Studies for Pharmaceutical and Parenteral Drug Products
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Arvind Singh Gusain, Subhash Chandra, Isaac Moura Araújo, João Paulo Martins de Lima and Henrique Douglas Melo Coutinho
Future Pharmacol. 2025, 5(2), 18; https://doi.org/10.3390/futurepharmacol5020018 - 12 Apr 2025
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Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they
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Purpose: Pharmaceutical parenteral drug products (PDPs) and orally inhaled nasal drug products (OINDPs) are critical medications for patient care, for which the route of administration is intravenous or oral/nasal inhalation, and the drug products directly infuse into the bloodstream or lungs, but they are categorized as high-risk for leachables. Method: These external foreign chemical substances (leachables) may adversely affect and alter patient safety. Results: These primary container closure systems and manufacturing process equipment mainly comprise rubber elastomers, polypropylene, resin, ink, adhesives, glass, or plastic material. To establish the ID of detected compounds and their quantity in the finished parenteral drug formulation and then to assess the formulation for toxicological safety, broad-scope non-specific analytical screening methods are required that are capable of screening out and quantifying the predicted/unpredicted leachable compounds at the levels that pose anticipated toxicological concerns for human patients. Before the selection of the final primary packaging system for the parenteral drug product, their extractable screening profile/knowledge is required to minimize leachable compounds in the finished drug product formulation and to develop and manufacture a safe product for human patients. The adverse effect or toxicity of leachables proportionally increases with an increase in the dose of the drug product or the duration of therapy because the volume of the drug product administered to a patient in a larger quantity is directly proportional to the concentration of the detected leachable. Conclusion: This document outlines the detailed process/scientific approach for conducting an organic leachable screening profile for parenteral drug products with respect to the chemical nature of leachables, i.e., polarity, propensity, volatility, and techniques.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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Open AccessReview
Anticancer Efficacy of Decursin: A Comprehensive Review with Mechanistic Insights
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Tanzila Akter Eity, Md. Shimul Bhuia, Raihan Chowdhury, Md. Arman Ali, Mst Muslima Khatun, Salehin Sheikh, Md. Sakib Al Hasan, Rubel Hasan, Ivo Cavalcante Pita Neto, Isaac Moura Araújo, Henrique D. M. Coutinho and Muhammad Torequl Islam
Future Pharmacol. 2025, 5(2), 17; https://doi.org/10.3390/futurepharmacol5020017 - 10 Apr 2025
Abstract
Introduction: Decursin is a pyranocoumarin natural phytochemical found in the Angelica gigas Nakai herb, which shows various therapeutic properties and beneficial effects against various diseases. Objective: The aim of this study was to find the anticancer potential of decursin and its molecular mechanisms
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Introduction: Decursin is a pyranocoumarin natural phytochemical found in the Angelica gigas Nakai herb, which shows various therapeutic properties and beneficial effects against various diseases. Objective: The aim of this study was to find the anticancer potential of decursin and its molecular mechanisms involved with different anticancer effects. Methodology: All of the relevant data concerning this compound and cancer were collected using different scientific search engines, including PubMed, Scopus, Springer Link, Wiley Online, Web of Science, Scifinder, ScienceDirect, and Google Scholar. Results: This study found that decursin shows anticancer properties through various mechanisms, such as apoptosis, cell cycle arrest, inhibition of cell proliferation, autophagy, inhibition of angiogenesis, cytotoxicity, and the inhibition of invasion and migration against a number of cancers, including breast, bladder, lung, colon, skin, ovarian, prostate, pancreatic, and bone cancers. This study also discovered that decursin has the ability to affect several signaling pathways in the molecular anticancer mechanisms, such as the PI3K/AKT/mTOR, JAK/STAT, and MAPK signaling pathways. Findings also revealed that decursin expresses poor oral bioavailability. Conclusions: Based on the data analysis from this literature-based study, decursin has properties to be considered as a potential candidate in the treatment of cancer. However, more clinical research is suggested to establish proper efficacy, safety, and human dosage.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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Open AccessArticle
Antioxidant Activity and Anxiolytic Effect of Cnidoscolus quercifolius Pohl Stem Bark Extract in Zebrafish
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Joice Barbosa do Nascimento, Johnatan Wellisson da Silva Mendes, José Jonas Ferreira Viturino, Maria Inácio da Silva, Mariana Pereira da Silva, Débora Odília Duarte Leite, Emmanuel Silva Marinho, Jane Eire Silva Alencar de Menezes, Hélcio Silva dos Santos and José Galberto Martins da Costa
Future Pharmacol. 2025, 5(2), 16; https://doi.org/10.3390/futurepharmacol5020016 - 5 Apr 2025
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Background: Cnidoscolus quercifolius, popularly known as “favela”, is used in traditional medicine to treat various conditions, such as infections and inflammations. However, its therapeutic potentials remain underexplored in scientific research. The present study aimed to evaluate the anxiolytic effect, toxicity, and
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Background: Cnidoscolus quercifolius, popularly known as “favela”, is used in traditional medicine to treat various conditions, such as infections and inflammations. However, its therapeutic potentials remain underexplored in scientific research. The present study aimed to evaluate the anxiolytic effect, toxicity, and antioxidant activity of methanolic (EMCq) and ethyl acetate (EAECq) extracts of C. quercifolius bark, as well as determine their chemical composition by HPLC/DAD and their levels of phenolic compounds and flavonoids. Methods: Anxiolytic effect and acute toxicity tests were conducted using the zebrafish model, while antioxidant activity was assessed using the DPPH• and ABTS+ methods. The chemical composition was obtained by HPLC/DAD, and phenolic compounds and flavonoids were quantified with the Folin–Ciocalteu reagents and the aluminum chloride colorimetric method, respectively. Results: Caffeic acid, p-coumaric acid, cinnamic acid, pinocembrin, and apigenin were identified and quantified. The results indicated that both extracts exhibited low antioxidant activity, possibly due to their low levels of phenols (0.187 and 0.293 mg GAE/g) and flavonoids (0.84 and 0.64 mg QE/g). However, the extracts did not show acute toxicity (>400 mg/kg) and reduced the locomotor activity of zebrafish at all the doses tested (40 to 400 mg/kg), while increasing the time the animals remained in the light zone, indicating an anxiolytic effect. Conclusions: These findings suggest for the first time that C. quercifolius has anxiolytic properties, warranting further investigation into specific bioactive compounds and their mechanisms of action. Future studies may explore molecular analysis techniques to identify the responsible compounds, as well as investigate safety and clinical efficacy in mammalian models.
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Open AccessArticle
Synergistic Antinociceptive Effects of Ketorolac and Ascorbic Acid in a Formalin-Induced Pain Model
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Josué Vidal Espinosa-Juárez, Erika Florecita Hoover-Lazo, Sergio de Jesús Rubio-Trujillo, Citlaly Natali de la Torre-Sosa, Nereida Violeta Vega-Cabrera, Josselin Carolina Corzo-Gómez, Refugio Cruz-Trujillo and Osmar Antonio Jaramillo-Morales
Future Pharmacol. 2025, 5(2), 15; https://doi.org/10.3390/futurepharmacol5020015 - 4 Apr 2025
Abstract
Pain is a widespread global issue and one of the most common disabling conditions in daily life. A wide range of medications are available to reduce or eliminate pain, with nonsteroidal anti-inflammatory drugs (NSAIDs) being among those most commonly used. Additionally, new analgesic
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Pain is a widespread global issue and one of the most common disabling conditions in daily life. A wide range of medications are available to reduce or eliminate pain, with nonsteroidal anti-inflammatory drugs (NSAIDs) being among those most commonly used. Additionally, new analgesic approaches, such as antioxidants (Ascorbic Acid), have been explored for their potential to relieve acute pain after surgery, cancer-related pain, and chronic pain not related to cancer with fewer adverse effects. Furthermore, the use of pharmacological combinations is an alternative treatment strategy to obtain a higher efficacy using lower drug concentrations, at which side effects are minimal. Background/Objectives: The aim of this study was to evaluate the pharmacological synergism of ketorolac and ascorbic acid in an inflammatory pain model. Methods: The individual and combined effects of ketorolac and ascorbic acid were evaluated in a formalin-induced pain model in mice. Four experimental groups were established: control (vehicle), ketorolac (KET), ascorbic acid (AA), and combination (KET/AA). Results: The combination of ketorolac and ascorbic acid produced a greater antinociceptive effect compared to the vehicle and individual treatments in the formalin model. Notably, even the lowest dose of the combination (KET 6.26/AA 3.21 µg/paw) exhibited a stronger effect than the maximum doses of each individual treatment KET (100 µg/paw) and AA (100 µg/paw). The effective concentration that produced 30% of antinociception (EC30) for the tested treatments were determined, and an isobologram analysis confirmed the presence of a synergistic interaction in these combinations. Conclusions: These findings suggest that the combination of ketorolac and ascorbic acid produces a synergistic antinociceptive effect in the formalin-induced pain model. The enhanced efficacy of the combination indicates a potential therapeutic advantage in pain management by reducing the required dosage of each compound while maintaining or improving analgesic effects.
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(This article belongs to the Special Issue Novel Therapeutic Approach to Inflammation and Pain)
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Open AccessReview
Trifluralin Toxicology Revisited: Microtubule Inhibition, Mitochondrial Damage, and Anti-Protozoan Potential
by
Darío Lirussi
Future Pharmacol. 2025, 5(2), 14; https://doi.org/10.3390/futurepharmacol5020014 - 23 Mar 2025
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The aim of this review is to evaluate the therapeutic possibilities of trifluralin and other 2,6-dinitroaniline herbicides by assessing different aspects of trifluralin’s toxicology (including its mitochondrial toxicity), pharmacokinetics, and environmental fate. The particular features of TFL have triggered a wide range of
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The aim of this review is to evaluate the therapeutic possibilities of trifluralin and other 2,6-dinitroaniline herbicides by assessing different aspects of trifluralin’s toxicology (including its mitochondrial toxicity), pharmacokinetics, and environmental fate. The particular features of TFL have triggered a wide range of policies about its properties. Is has been banned in some countries and, at the same time, has been proposed as a drug for the cure of parasitic disease by some scientific research articles. The use of this pre-emergence herbicide to control broadleaf weeds and annual grasses is assumed to rely only on its microtubule depolarization or cytoskeleton disassembly abilities (on-target effect), a fact that justifies its inhibition of a wide range of microorganisms (mostly protozoans), sharing a relatively high degree of conservation in tubulin protein sequences with weeds and grasses. Recent studies have confirmed that TFL also affects mitochondrial function (off-target effect), a hypothesis previously suggested in earlier works. Here, we account for the main issues in TFL toxicology, other potential uses of the herbicide outside crops, and its feasibility for use as an antiprotozoal drug.
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Open AccessArticle
Interaction of Microcolin Cyanobacterial Lipopeptides with Phosphatidylinositol Transfer Protein (PITP)—Molecular Docking Analysis
by
Christian Bailly and Gérard Vergoten
Future Pharmacol. 2025, 5(1), 13; https://doi.org/10.3390/futurepharmacol5010013 - 17 Mar 2025
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Background/Objectives: Microcolins A–M are cytotoxic marine lipopeptides produced by the cyanobacterium Moorena producens, also known as Lyngbya majuscula. Recent studies have shown that two compounds in the series, microcolins B and H, can form covalent complexes with phosphatidylinositol transfer proteins α and
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Background/Objectives: Microcolins A–M are cytotoxic marine lipopeptides produced by the cyanobacterium Moorena producens, also known as Lyngbya majuscula. Recent studies have shown that two compounds in the series, microcolins B and H, can form covalent complexes with phosphatidylinositol transfer proteins α and β (PITPα/β) upon the reaction of their α,β-unsaturated ketone group with the thiol group of a key cysteine residue of PITP. These observations prompted us to compare the binding of all microcolins and a few related derivatives (VT01454 and (deoxy)majusculamide D) to PITP to delineate structure–binding relationships. Methods: A molecular docking analysis led to the identification of microcolin E as the potentially best PITPα binder in the series, followed by microcolins B and H and analog VT01454. The computational data agree well with the published experimental results. Results: The binding of microcolin H into a large cavity of PITPα positions its reactive electrophilic α,β-unsaturated ketone close to the thiol of Cys95, enabling the facile formation of a covalent C-S linkage. A similar bonding can occur with the Cys94 of PITPβ. Molecular models of microcolins bound to PITP were compared to identify structural elements chiefly implicated in the recognition process. Conclusions: This computational study provides guidance in the design of microcolin derivatives targeting PITPα/β considered targets for cancer and inflammatory pathologies.
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Open AccessArticle
Effects of Sinensetin, Eupatilin, and Jaceosidin on Human Melanogenesis: A Pilot Study
by
Shilpi Goenka
Future Pharmacol. 2025, 5(1), 12; https://doi.org/10.3390/futurepharmacol5010012 - 14 Mar 2025
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Background/Objectives: Flavones, a class of plant-based flavonoids, have demonstrated conflicting anti-melanogenic activities in mouse and human melanocytes. Sinensetin (SNT), a polymethoxyflavone, has shown pro-melanogenic activity in B16F10 mouse melanoma (MM) cells, while eupatilin (EU) and jaceosidin (JAC), two flavones that are structural analogs
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Background/Objectives: Flavones, a class of plant-based flavonoids, have demonstrated conflicting anti-melanogenic activities in mouse and human melanocytes. Sinensetin (SNT), a polymethoxyflavone, has shown pro-melanogenic activity in B16F10 mouse melanoma (MM) cells, while eupatilin (EU) and jaceosidin (JAC), two flavones that are structural analogs of SNT, have not been evaluated for their effects on melanogenesis yet. Methods: Herein, the effects of SNT, EU, and JAC on melanogenesis in MNT-1 cells (human melanoma) and HEMn-DP cells (primary human melanocytes) have been examined. The mushroom tyrosinase (TYR) activity was tested in cell-free conditions, followed by examination of the cytotoxicity of the compounds via the Alamar Blue (AB) assay. Cellular melanin production and TYR activity were estimated in MNT-1 cells. The compounds were further examined in primary human melanocytes for melanin production, TYR activity, and protein levels. Results: Our findings show that SNT was a potent inhibitor of TYR activity in a cell-free assay, while EU and JAC had no effect. However, both SNT and EU were shown to exhibit anti-melanogenic activity (that was reversible) in human cells, while JAC was ineffective and cytotoxic. Conclusions: SNT and EU are potential novel candidates for hyperpigmentation treatment without cytotoxicity. Additional studies are warranted to elucidate the signaling mechanisms that govern their anti-melanogenesis action. Future research is necessary to assess the anti-melanogenic effectiveness of SNT/EU using 3D skin tissue equivalents and to select the optimal candidate.
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Open AccessReview
Inter-Tissue Communication Mechanisms via Exosomes and Their Implications in Metabolic Diseases: Opportunities for Pharmacological Regulation
by
Brenda Chimal-Vega, Jesus Emanuel Maldonado-Arvizu, Alex Daniel Hernández Avalos, José Fernando Díaz-Villanueva, Luis Pablo Avila-Barrientos and Victor G. García González
Future Pharmacol. 2025, 5(1), 11; https://doi.org/10.3390/futurepharmacol5010011 - 6 Mar 2025
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Exosomes can transport regulatory biomolecules and are mediators of cellular signaling among metabolic tissues through endocrine mechanisms. Understanding the pathways and processes underlying exosome-mediated inter-tissue communication is critical for elucidating the molecular pathophysiology of metabolic diseases such as obesity, type 2 diabetes mellitus
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Exosomes can transport regulatory biomolecules and are mediators of cellular signaling among metabolic tissues through endocrine mechanisms. Understanding the pathways and processes underlying exosome-mediated inter-tissue communication is critical for elucidating the molecular pathophysiology of metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and cardiovascular disorders. Consequently, these mechanisms represent novel and promising targets for pharmacological regulation. We examined the current knowledge regarding exosome physiology, the mechanisms of interaction with target tissues, and its role in metabolic tissue communication. We also analyzed the secretory profiles of exosomes in metabolic tissues, emphasizing their regulatory roles in adipose tissue, liver, pancreas, skeletal muscle, and the small intestine, while discussing their association with metabolic diseases. In this sense, we propose the exosomal pentad as a novel framework highlighting exosome-mediated inter-organ communication, where exosomes may regulate a metabolic axis involving these tissues. This model aligns with the ominous octet in type 2 diabetes but emphasizes exosomes as key regulators of metabolic homeostasis and potential therapeutic targets. The role of exosomes for the treatment of metabolic diseases emerges as a critical area of pharmacologic exploration. For instance, therapeutic strategies that prevent target tissue binding or expression of cargo molecules such as miRNAs could be designed, using antagomiRs or nanoparticles. Additionally, integrins like αvβ5 on the exosomal membrane can be blocked with monoclonal antibodies or engineered for targeted delivery of therapeutic molecules. Exosomes, critical mediators of inter-organ communication and metabolic regulation, hold potential to design precise molecular-level therapies while minimizing systemic side effects.
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Open AccessArticle
Water-Soluble Cu(II) Complexes with Polypyridyl Ligands: Anticancer Activity and DNA Interaction
by
Herisson F. dos Santos, Nádija N. P. da Silva, George B. S. Pereira, Mauro A. Lima, Nailton M. Nascimento-Júnior, Renan L. de Farias, Amos O. Akinyemi and Fillipe V. Rocha
Future Pharmacol. 2025, 5(1), 10; https://doi.org/10.3390/futurepharmacol5010010 - 19 Feb 2025
Abstract
Background/Objectives: Cu(II) complexes with polypyridine ligands have shown carcinogenic activity already described in the literature and appear as a possible alternative to cisplatin, which has several side effects. In view of this, four Cu(II) complexes with the formulas [Cu(L1)(H2O)2](PF
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Background/Objectives: Cu(II) complexes with polypyridine ligands have shown carcinogenic activity already described in the literature and appear as a possible alternative to cisplatin, which has several side effects. In view of this, four Cu(II) complexes with the formulas [Cu(L1)(H2O)2](PF6)2 (A1) and [Cu(L2)(H2O)2](PF6)2 (A2), [Cu(L1)(bipy)](PF6)2 (B1) and [Cu(L2)(bipy)](PF6)2 (B2) were synthesized, where L1 = dipyrido[1,2,5]oxadiazolo[3,4-b]quinoxaline, L2 = 6,7-dicyanodipyrido[2,2-d:2,3-f]quinoxaline, and bipy = 2,2′-bipyridine. Methods: The proposed structures supported characterization techniques (molar conductivity, elemental analyses, absorption spectroscopy in the infrared region, and UV–vis). The interaction of the complexes with DNA was evaluated through an ethidium bromide displacement assay, complemented by theoretical studies using molecular docking. Additionally, the cytotoxic activity of the complexes was tested against DU 145 (prostate tumor), MCF-7 (breast tumor), and PNT-2 (non-tumor prostate) cell lines, with all complexes showing promising results. Results: Among them, complex B1 exhibited the highest number of DNA contacts in molecular docking studies, a binding constant of 3.7 × 106 in the ethidium bromide displacement assay. It was the most selective complex (IS = 5.43) for the DU 145 (prostate tumor) cell line, demonstrating greater selectivity than cisplatin. Conclusions: This study has demonstrated the potential of the Cu(II) complexes obtained, which could be an alternative to platinum complexes in the future
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2024)
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Open AccessArticle
Discovery of Arylfuran and Carbohydrate Derivatives from the BraCoLi Library as Potential Zika Virus NS3pro Inhibitors
by
Fernanda Kelly Marcelino e Oliveira, Beatriz Murta Rezende Moraes Ribeiro, Ellen Gonçalves de Oliveira, Marina Mol Sena Andrade Verzola, Thales Kronenberger, Vinícius Gonçalves Maltarollo, Ricardo José Alves, Renata Barbosa de Oliveira, Rafaela Salgado Ferreira, Jônatas Santos Abrahão and Mateus Sá Magalhães Serafim
Future Pharmacol. 2025, 5(1), 9; https://doi.org/10.3390/futurepharmacol5010009 - 15 Feb 2025
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Background/Objectives: Zika fever is a disease caused by the Zika virus (ZIKV). Symptomatic cases may be associated with neurological disorders in adults, as well as congenital Zika syndrome and other birth defects during pregnancy. In 2016, Zika fever was considered a public health
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Background/Objectives: Zika fever is a disease caused by the Zika virus (ZIKV). Symptomatic cases may be associated with neurological disorders in adults, as well as congenital Zika syndrome and other birth defects during pregnancy. In 2016, Zika fever was considered a public health problem by the World Health Organization (WHO), highlighting the need to develop new therapies against the disease. Currently, there is no antiviral or vaccine available to treat or prevent severe cases. Due to the lack of available therapeutics and few promising hit molecules, we computationally screened the well-described ZIKV protease (NS3pro) as a drug target to revisit the small-molecule database Brazilian Compound Library (BraCoLi) and select potential inhibitors. Methods: We employed a consensus docking screening of a library of 1176 compounds using GOLD and DockThor. We selected 28 hits based on predicted binding affinity, and only the remnants of three compounds were available in the library at the time of this study for experimental validation. The hits were evaluated for their cytotoxic (CC50) and effective concentrations (EC50) for their potential antiviral activity in Vero cells. Results: The three hit compounds presented modest CC50 values of 89.15 ± 3.72, >100, and 29.67 ± 1.01 μM, with the latter, a carbohydrate derivative, having an EC50 value of >12.5 μM (~40% inhibition) against ZIKV PE243. Additionally, the essentially non-toxic compound, an arylfuran derivative, also inhibited the ZIKV NS3pro with an IC50 value of 17 μM but presented evidence of acting through a promiscuous mechanism for enzyme inhibition. Conclusion: This study highlights the relevance of revisiting existing small-molecule assets to identify novel therapeutic starting points against ZIKV, aiming for potential lead candidates in the future.
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Open AccessCommunication
The Effect of Agave Bagasse Extract on Wound Healing in a Murine Model
by
Herminia López-Salazar, Elizabeth Negrete-León, Brenda Hildeliza Camacho-Díaz, Juan José Acevedo-Fernández, Sandra Victoria Ávila-Reyes and Martha L. Arenas Ocampo
Future Pharmacol. 2025, 5(1), 8; https://doi.org/10.3390/futurepharmacol5010008 - 5 Feb 2025
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Background/Objectives: The development of bioproducts that can accelerate wound healing is a key focus in biomedicine, especially when these products are derived from sustainable by-products. This study investigates the wound-healing potential of an extract obtained from Agave angustifolia Haw bagasse (BagEE) using microwave
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Background/Objectives: The development of bioproducts that can accelerate wound healing is a key focus in biomedicine, especially when these products are derived from sustainable by-products. This study investigates the wound-healing potential of an extract obtained from Agave angustifolia Haw bagasse (BagEE) using microwave extraction.Methods: HPLC-MS analysis was performed to identify the main compounds present in BagEE, revealing quercetin, isorhamnetin, diosgenin, hecogenin, manogenin, β-sitosterol glucoside, and β-sitosterol as tentative constituents. A murine excision wound model was employed to assess the efficacy of BagEE. The experimental group received a topical application of 8 mg of BagEE, while the control group was treated with water only. Wound closure, re-epithelialization, and collagen deposition were evaluated to determine the effects of BagEE on skin healing. Results: The BagEE-treated group exhibited significantly accelerated wound healing, achieving a 99.4% closure rate by day 13 compared to the control group’s 92.8% closure rate on day 22. Additionally, wounds treated with BagEE displayed complete re-epithelialization and a well-organized skin structure. Conclusions: These findings suggest that BagEE promotes effective wound healing and shows promise as a topical agent for skin regeneration. Further studies are necessary to investigate its anti-inflammatory and wound-healing activities in both in vivo and in vitro settings.
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