Current Research in Pharmacology and Drug Discovery最新文献

{"title":"Cardiac injury elicited by sub-chronic hookah smoke inhalation, and the alleviating effect of procysteine, 2-oxo-(4R)-4-thiazolidinecarboxylic acid, in BALB/c mice","authors":"Sumaya Beegam ,&nbsp;Suhail Al-Salam ,&nbsp;Bilal M. Nemmar ,&nbsp;Nur Elena Zaaba ,&nbsp;Ozaz Elzaki ,&nbsp;Badreldin H. Ali ,&nbsp;Abderrahim Nemmar","doi":"10.1016/j.crphar.2026.100252","DOIUrl":"10.1016/j.crphar.2026.100252","url":null,"abstract":"<div><div>Hookah smoke (HS) inhalation is known to induce cardiovascular dysfunction, including oxidative stress and inflammation. The procysteine, 2-oxo-(4R)-4-thiazolidinecarboxylic acid (OTC) is a prodrug of cysteine, a precursor of glutathione, which is a major intracellular antioxidant. This study aimed to evaluate the possible cardioprotective effects of OTC against HS inhalation-induced cardiac injury in mice. The animals were exposed to HS for 30 min per day, five days per week, for one month, while control mice were exposed to normal air. OTC was administered by gavage at a dose of 80 mg/kg 1 h before each exposure session. OTC prevented HS-induced increase in the concentrations of tumor necrosis factor α, interleukin (IL)-6 and galectin-3 in the heart tissue. HS exposure augmented the levels of markers of oxidative stress and adhesion molecules. The latter effects were significantly abrogated by OTC treatment. Likewise, the cardiac DNA damage and apoptosis triggered by HS inhalation were significantly prevented in mice treated with OTC. The concentrations of NLRP3 inflammasome and IL-1β in the hearts of mice exposed to HS were significantly augmented, and OTC treatment significantly abated this effect. Moreover, while the cardiac expression of phosphorylated nuclear factor κB (NF-κB) was increased, that of sirtuin-1 was significantly decreased by HS inhalation. Both effects were significantly mitigated by OTC administration. Furthermore, HS inhalation induced an elevation in the concentrations of mammalian targets of rapamycin and nuclear factor erythroid-derived 2-like 2 (Nrf2) expression in the heart, and this effect was significantly potentiated in the OTC + HS group. Despite these molecular and biochemical alterations, no detectable differences in cardiac histology were observed among the experimental groups. Collectively, these findings demonstrate that OTC mitigates HS-induced cardiac injury by reducing oxidative stress, inflammation, DNA damage, and apoptosis through mechanisms that involve inhibition of NLRP3 inflammasome activation and NF-κB signaling, together with activation of sirtuin-1 and Nrf2 pathways.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100252"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRPS and PKS pathways in actinomycetes: A review of biosynthetic diversity and bioactive potential","authors":"Abhishek Chauhan ,&nbsp;Manisha Gurnani ,&nbsp;Jayati Arora ,&nbsp;Ritu Chauhan ,&nbsp;Anuj Ranjan ,&nbsp;Naveen Chandra Joshi ,&nbsp;Laurent Dufossé ,&nbsp;Tanu Jindal","doi":"10.1016/j.crphar.2026.100254","DOIUrl":"10.1016/j.crphar.2026.100254","url":null,"abstract":"<div><div>Actinomycetes are Gram-positive bacteria renowned for their capacity to produce chemically diverse secondary metabolites with significant pharmaceutical relevance. Widely distributed across marine and terrestrial environments, they exhibit remarkable metabolic adaptability that supports the synthesis of novel compounds under environmental stress. This review examines the biosynthetic diversity of actinomycetes, with a focus on non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), the principal enzymatic systems responsible for complex metabolite assembly. A clear distinction is made between synthetases (ATP-dependent enzymes such as NRPSs) and synthases (ATP-independent enzymes such as PKSs), addressing a key conceptual ambiguity. The modular architecture of NRPSs, including adenylation, thiolation, and condensation domains, is discussed in relation to peptide biosynthesis, while PKS systems are outlined based on their classification (Types I–III), domain organization, and chain elongation mechanisms. Hybrid PKS–NRPS pathways and inter-domain interactions are further highlighted for their role in expanding chemical diversity. Collectively, these biosynthetic systems highlight the potential of actinomycetes as a rich source of therapeutically relevant compounds, particularly in antimicrobial and anticancer drug discovery.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100254"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147747520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking biofilm barriers in skin wounds: Membrane-Active antimicrobials in an era of resistance","authors":"Lisa Myrseth Hemmingsen ,&nbsp;Nataša Škalko-Basnet","doi":"10.1016/j.crphar.2025.100249","DOIUrl":"10.1016/j.crphar.2025.100249","url":null,"abstract":"<div><div>Chronic wounds remain a significant challenge for healthcare systems worldwide, placing a considerable burden on both patients and resources. Their management is further complicated by the persistence of biofilm-forming bacteria and an escalating problem of antimicrobial resistance, both of which restrict the effectiveness of conventional therapies. Antimicrobial compounds with a rapid onset of action and activity that is not solely dependent on bacterial metabolism represent promising alternatives for bacterial and biofilm eradication. Among these, membrane-active antimicrobials (MAAs), including antimicrobial peptides, peptidomimetics, and other membrane-disrupting compounds, constitute a particularly interesting group of agents. Recent investigations have revealed diverse mechanisms through which MAAs compromise biofilm integrity, ranging from permeabilization of bacterial membranes to interference with quorum sensing and extracellular polymeric substances. Furthermore, pharmaceutical innovations such as nanoparticle-based carriers, hydrogel matrices, and scaffold-based delivery systems have shown potential to enhance MAA stability, optimize and prolong release profiles, improve antimicrobial and anti-biofilm efficacy, increase tissue penetration, and mitigate cytotoxicity concerns. By integrating insights from microbiology, materials science, and drug development, this short review aims to outline the challenges posed by biofilms in chronic wounds, appraise the antimicrobial and anti-biofilm activity of MAAs, and discuss how advanced delivery strategies might expand their clinical efficacy.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100249"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of naringenin on nicotine-induced anxiety and depression: Involvement of monoaminergic systems, oxidative stress, and neuroinflammation on male rats","authors":"Murtaza Haidary ,&nbsp;Yahya Samadi ,&nbsp;Zakaria Rezai ,&nbsp;Atiqullah Sadaqat ,&nbsp;Mohammad Ali Ahmadi ,&nbsp;Jamshid Gholami ,&nbsp;Mohammad Mahdi Mohammadi ,&nbsp;Mohammad Taqi Shojae","doi":"10.1016/j.crphar.2025.100242","DOIUrl":"10.1016/j.crphar.2025.100242","url":null,"abstract":"<div><h3>Introduction</h3><div>Nicotine withdrawal during adolescence induces severe neurobehavioral disturbances and neurochemical alterations, including anxiety, depression, affective dysregulation, oxidative stress, and neuroinflammation. Current therapeutic options for managing nicotine dependence remain suboptimal. This study investigated the neuroprotective potential of naringenin (NG) in alleviating behavioral and biochemical sequelae of nicotine withdrawal in adolescent rats.</div></div><div><h3>Materials and methods</h3><div>Male adolescent Wistar rats were allocated into eight groups and subjected to nicotine exposure (1 mg/kg) and NG treatment (50 or 100 mg/kg) across nicotine exposure and withdrawal phases. Behavioral assays (OFT, EPM, FST) were employed to evaluate anxiety- and depression-like behaviors. Neurochemical assessments of dopamine, serotonin, their metabolites (DOPAC, 5-HIAA), MAO-A activity, oxidative stress markers (MDA, Nit), antioxidant enzymes (SOD, CAT, TT), and neuroinflammatory/neurodegenerative biomarkers (GFAP, IL-10, BDNF, NSE) were conducted in prefrontal cortex (PFC) homogenates.</div></div><div><h3>Results</h3><div>Nicotine withdrawal significantly induced anxiety- and depression-like behaviors, disrupted monoaminergic balance, elevated MAO-A activity, and triggered oxidative and neuroinflammatory responses in the PFC. NG administration, particularly at 100 mg/kg across both phases, significantly ameliorated behavioral impairments, restored neurotransmitter homeostasis, inhibited MAO-A, suppressed lipid peroxidation and nitrosative stress, enhanced antioxidant defenses, reduced GFAP and NSE expression, and restored IL-10 and BDNF levels.</div></div><div><h3>Conclusion</h3><div>NG exerts anxiolytic, antidepressant, antioxidant, and anti-inflammatory effects, likely via modulation of monoaminergic pathways and suppression of neuroinflammation and oxidative stress. These findings underscore the potential of NG as a promising candidate for mitigating neuropathological effects associated with nicotine withdrawal-induced neuropathology, particularly during adolescence.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100242"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of oxaliplatin and nanocurcumin in dendrosomal carrier to inhibits ovarian cancer cells invasion and metastasis through the long non-coding RNA MEG3","authors":"Elahe Seyed Hosseini ,&nbsp;Marziyeh Alizadeh Zarei ,&nbsp;Zahra Shabani ,&nbsp;Hamed Haddad Kashani ,&nbsp;Hossein Nikzad","doi":"10.1016/j.crphar.2025.100243","DOIUrl":"10.1016/j.crphar.2025.100243","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer (OC) remains one of the most lethal gynecological malignancies worldwide. The long non-coding RNA MEG3 (Maternally Expressed Gene 3), located on chromosome 14q32.3, has been identified as a tumor suppressor in various cancers. This study investigated the impact of siRNA-mediated MEG3 silencing in the context of dendrosomal nanocurcumin (DNC) and Oxaliplatin (OXA) treatments on ovarian cancer cell lines, focusing on the expression of genes associated with apoptosis and metastasis, including Bcl-2, BAX, MMP-2, and MMP-9.</div></div><div><h3>Methods</h3><div>Cell viability was assessed using the MTT assay; apoptosis and cell cycle progression were evaluated via flow cytometry and Annexin V-FLUOS staining. Cell migration and invasion were examined using the transwell assay, and gene expression levels were quantified by real-time PCR.</div></div><div><h3>Results</h3><div>MEG3 expression significantly increased in both cell lines upon DNC and OXA treatment in a time-dependent manner, with the most pronounced effect in OVCAR3 cells (P &lt; 0.01–0.001). MEG3 silencing significantly attenuated the anticancer efficacy of both agents. Notably, MMP-2 expression increased in DNC (P &lt; 0.01) and combination therapy (P &lt; 0.001), while MMP-9 was upregulated following OXA treatment (P &lt; 0.01) after MEG3 knockdown.</div></div><div><h3>Conclusion</h3><div>These results suggest that MEG3 knockdown impairs the anti-metastatic properties of DNC and OXA by modulating MMP-2 and MMP-9 expression. The combination of DNC and OXA holds promise as an effective therapeutic strategy in OC, and MEG3 may serve as a potential biomarker and therapeutic target, particularly in drug-resistant ovarian cancer.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100243"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145747033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential, pharmacological role and molecular mechanisms of adelmidrol, an analogue of palmitoylethanolamide","authors":"Bushra Zia ,&nbsp;Abdulrahman Alkaabi ,&nbsp;Niraj Kumar Jha ,&nbsp;Sameer Mirza ,&nbsp;Sandeep B Subramanya ,&nbsp;Shreesh Ojha","doi":"10.1016/j.crphar.2026.100250","DOIUrl":"10.1016/j.crphar.2026.100250","url":null,"abstract":"<div><div>Adelmidrol is a bioactive semi-synthetic compound with significant therapeutic potential, particularly in resolving inflammation since inflammation plays a key role in the pathogenesis of several diseases. The mechanisms of action of adelmidrol are multifaceted, involving interactions with specific receptors like the PPAR-γ and modulation of signaling pathways associated with inflammation. Adelmidrol demonstrates efficacy in conditions such as inflammatory bowel disease, colon inflammation, and urothelial inflammation by regulating the level of pro-inflammatory cytokines. In dermatological conditions like atopic and allergic dermatitis, adelmidrol plays a key role in modulating immune responses and enhancing skin barrier function by reducing inflammation while offering an alternative to conventional therapies. Additionally, adelmidrol plays a critical role in wound healing and diabetic foot ulcers by facilitating cell migration and proliferation, thus accelerating wound closure and reducing infection risk. Adelmidrol has been shown to reduce joint inflammation and improve functionality, making it a candidate for adjunct therapy in musculoskeletal disorders like osteoarthritis. The compound also addresses pulmonary conditions, such as pulmonary fibrosis, by mitigating inflammatory responses and improving respiratory function. Furthermore, applications of adelmidrol in liver diseases, including liver ischemia and non-alcoholic steatohepatitis (NASH), highlight its potential in resolving hepatic inflammation. This review emphasizes the therapeutic promise of adelmidrol across various inflammatory diseases, advocating for further clinical studies to establish its full potential and optimize its clinical use all the while providing an overview of the properties, mechanisms of action, and therapeutic applications of adelmidrol.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100250"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Pharmacogenetics association with long-term clinical evolution in a kidney transplant patients cohort” [Curr. Res. Pharmacol. Drug Discov. 9 (2025) 100230]","authors":"Luis Sendra ,&nbsp;Gladys G. Olivera-Pasquini ,&nbsp;Enrique G. Zucchet ,&nbsp;Fabiana D.V. Genvigir ,&nbsp;María Isabel Beneyto ,&nbsp;Julio Hernández-Jaras ,&nbsp;María José Herrero ,&nbsp;Salvador F. Aliño","doi":"10.1016/j.crphar.2025.100247","DOIUrl":"10.1016/j.crphar.2025.100247","url":null,"abstract":"","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100247"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146184663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arctiin targets oxidative stress and inflammation, restores Neuregulin-1, and improves neurobehavioral outcomes in neonatal hypoxic-ischemic brain injury","authors":"Skandar Babak ,&nbsp;Tahereh Safari ,&nbsp;Hamed Fanaei","doi":"10.1016/j.crphar.2026.100253","DOIUrl":"10.1016/j.crphar.2026.100253","url":null,"abstract":"<div><h3>Objective</h3><div>Hypoxic-ischemic brain damage (HIBD) represents a major cause of neonatal morbidity and mortality, resulting from perinatal oxygen deprivation and impaired cerebral blood flow. This study aims to investigate the neuroprotective effects of Arctiin, a bioactive lignan derived from <em>Arctium lappa</em>, recognized for its potent antioxidant and anti-inflammatory properties, in a neonatal rat model of HIBD.</div></div><div><h3>Materials and methods</h3><div>Neonatal rats at postnatal day 8 were randomly assigned to four groups: Sham-operated (SHAM), Hypoxia-Ischemia (HI), Hypoxia-Ischmia with Solvent control (HI/SO), and Hypoxia-Ischemia treated with Arctiin (HI/Arc). HIBD was induced via unilateral carotid artery ligation followed by exposure to hypoxia. The HI/Arc group was administered Arctiin orally at a dosage of 60 mg/kg daily for seven consecutive days. Behavioral performance, biochemical parameters, histological integrity, and gene expression profiles were assessed to evaluate the neuroprotective efficacy of Arctiin.</div></div><div><h3>Results</h3><div>Arctiin administration resulted in a significant reduction in C-reactive protein (CRP), and total oxidant capacity (TOC). Simultaneously, it enhanced total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF) levels. Histological analysis showed diminished infarct volume in the Arctiin-treated group. Moreover, gene expression studies revealed significant restoration of Neuregulin-1 (NRG-1) in group treated by arctiin. Neurobehavioral assessments further confirmed significant improvements in sensorimotor function in the Arctiin-treated group.</div></div><div><h3>Conclusion</h3><div>Our study provides evidence indicating that Arctiin mitigates hypoxic-ischemic brain damage in rat pups through a synergistic mechanism involving the suppression of inflammation and oxidative stress, coupled with the upregulation of critical neuroprotective genes and proteins, specifically NRG-1 gene expression and BDNF protein levels. Future studies should investigate the precise molecular pathways downstream of NRG-1 that mediate Arctiin's neuroprotective effects.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100253"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desloratadine attenuates renal ischemia-reperfusion injury through activation of the Nrf2-GCL-GSH antioxidant pathway","authors":"Firouzeh Gholampour,&nbsp;Atefeh Maghsoodi,&nbsp;Khojasteh Malekmohammad","doi":"10.1016/j.crphar.2026.100255","DOIUrl":"10.1016/j.crphar.2026.100255","url":null,"abstract":"<div><div>Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) in transplantation and major surgery, with limited effective pharmacological interventions. This study evaluated the prophylactic effect of desloratadine, a second-generation H1-receptor antagonist with anti-inflammatory and antioxidant properties, on renal IRI. Twenty-one male Sprague–Dawley rats were randomly assigned to three groups (n = 7 each): Sham, I/R (45 min ischemia followed by 24 h reperfusion), and I/R + desloratadine (5 mg/kg, orally, 1 h prior to ischemia). After 24 h of reperfusion, renal function, oxidative stress markers, histopathology, and antioxidant gene expression were assessed. I/R significantly impaired renal function (increased plasma creatinine and urea, decreased creatinine clearance; <em>P</em> &lt; 0.001), reduced effective free-water reabsorption, and increased oxidative stress (elevated TOS, reduced TAC and GSH; <em>P</em> &lt; 0.01–0.001). Desloratadine significantly improved renal function, restored tubular concentrating ability, reduced oxidative stress, and increased GSH levels (<em>P</em> &lt; 0.05–0.001 vs. I/R). At the molecular level, I/R upregulated Nrf2 and HO-1 expression but downregulated Gclc and Gclm, while desloratadine further enhanced Nrf2/HO-1 expression and restored Gclc/Gclm levels. Histological analysis confirmed attenuation of tubular injury. In conclusion, desloratadine pretreatment is associated with protection against renal IRI, potentially through modulation of the Nrf2–GCL–GSH antioxidant pathway and preservation of tubular function. These findings support its potential repurposing as an adjuvant strategy in settings at risk of renal ischemic injury.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100255"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147747519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Shigella activity and killing kinetics of compounds from MMV Pathogen and COVID Boxes: Identifying leads against Shigellosis","authors":"Lauve Rachel Tchokouaha Yamthe ,&nbsp;Francine Kengne Mediesse ,&nbsp;Yanick Kevin Melogmo Dongmo ,&nbsp;Sonia Raissa Matchuenkam Gayap ,&nbsp;Darline Dize ,&nbsp;Patrick Valere Tsouh Fokou ,&nbsp;Fabrice Fekam Boyom","doi":"10.1016/j.crphar.2026.100251","DOIUrl":"10.1016/j.crphar.2026.100251","url":null,"abstract":"<div><h3>Background</h3><div>Shigellosis is a leading diarrheal disease, posing critical public health challenges in low- and middle-income countries. Rising antibiotic resistance exacerbates treatment limitations.</div></div><div><h3>Methods</h3><div>We screened 560 compounds from the MMV Pathogen and COVID Boxes for <em>in vitro</em> activity against <em>Shigella flexneri</em>, <em>S. sonnei</em>, and <em>S. dysenteriae</em> via resazurin-based microdilution. Cytotoxicity (RAW 264.7 cells) and killing kinetics against <em>S. flexneri</em> were assessed.</div></div><div><h3>Results</h3><div>From the primary screen, 13 compounds (9 from the Pathogen Box, 4 from the COVID Box) showed potent anti-<em>Shigella</em> activity against <em>S. flexneri</em> (MIC ≤10 μM). Among these, seven non-antibiotic Pathogen Box compounds exhibited low-micromolar MICs (0.31–5 μM) and low cytotoxicity (CC₅₀ &gt; 100 μM). The known antibiotic levofloxacin (MMV687798) showed broad-spectrum activity (MIC 0.15–2.5 μM). MMV1804312 (salinomycin) was the most active COVID Box hit (MIC 1.25 μM). Time-kill assays revealed rapid, concentration-dependent bactericidal activity (≥3-log reduction within 4–6 h) for Pathogen Box compounds MMV675997 and MMV021660, while MMV000858 displayed bacteriostatic action.</div></div><div><h3>Conclusion</h3><div>This study identifies several novel, non-antibiotic leads from the MMV Pathogen Box with potent anti-<em>Shigella</em> activity and favorable cytotoxicity profiles, offering promising starting points for further development against drug-resistant shigellosis.</div></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"10 ","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146184664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}