Pharmacological Reports最新文献

{"title":"Retraction Note: Renal protective effect of nebivolol in rat models of acute renal injury: role of sodium glucose co-transporter 2.","authors":"Ahmed M Nasr, Samar Rezq, Aya Shaheen, Shimaa M Elshazly","doi":"10.1007/s43440-026-00886-y","DOIUrl":"https://doi.org/10.1007/s43440-026-00886-y","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol (CBD) modulates the serotonin-kynurenine metabolic balance in the brain of morphine-tolerant neuropathic rats.","authors":"Sofia Nasini, Leora Pearl-Dowler, Martha Lopez-Canul, Luca Posa, Antonella Bertazzo, Gabriella Gobbi, Stefano Comai","doi":"10.1007/s43440-026-00850-w","DOIUrl":"10.1007/s43440-026-00850-w","url":null,"abstract":"<p><p>BACKGROUND: Neuropathic pain (NP) is a chronic and debilitating condition that remains difficult to treat, with opioids like morphine often leading to tolerance and reduced efficacy over time. Cannabidiol (CBD) has emerged as a potential therapeutic for NP even in morphine tolerance conditions; however, its effects on nociceptive modulation and neurotransmitter metabolism in morphine-tolerant NP models remain poorly understood. This study investigated the impact of CBD on mechanical hypersensitivity and on tryptophan (TRP) metabolism via the serotonin (5-HT) and kynurenine (KYN) pathways and dopamine (DA) in Wistar rats with NP and morphine tolerance. METHODS: NP was induced using the spared nerve injury (SNI) model. Animals received morphine (5 mg/kg, subcutaneous (sc), twice daily) for 7 days to induce tolerance. On Day 8, rats were treated with CBD (20 mg/kg, ip) or vehicle. Mechanical hypersensitivity was assessed, and TRP metabolism and DA were evaluated in different brain regions and serum. RESULTS: Repeated morphine induced tolerance to its analgesic effects. CBD significantly reduced mechanical hypersensitivity in non-tolerant rats, with a modest effect in morphine-tolerant animals. In tolerant rats, CBD increased 5-hydroxytryptophan (5-HTP)/TRP ratio in hippocampus and midbrain and reduced KYN levels in the hippocampus, indicating a shift toward 5-HT synthesis. CBD also lowered DA and the 5-HTP/TRP ratio in the brainstem, and decreased serum TRP and 5-HT. CONCLUSIONS: CBD treatment in NP morphine-tolerant rats exerted a modest effect on mechanical hypersensitivity and was associated with a partial counteraction of metabolic dysregulation by reducing KYN production and shifting TRP metabolism toward 5-HT synthesis (increased 5-HTP/TRP ratio). These findings suggest that CBD modulates 5-HT tone through region-specific mechanisms associated with the development of morphine tolerance. </p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"731-747"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The extensive erythrocyte-plasma partitioning of trametinib - implications for pharmacokinetic studies and therapeutic drug monitoring.","authors":"Bence János Chriszt, Zoltán Köllő, Orsolya Geda, Éva Csöndör, Róbert Farkas, Barna Vásárhelyi, Miklós Garami, Gellért Balázs Karvaly","doi":"10.1007/s43440-026-00840-y","DOIUrl":"10.1007/s43440-026-00840-y","url":null,"abstract":"<p><p>BACKGROUND: Trametinib (TRT) is a kinase inhibitor displaying extensive erythrocyte-plasma partitioning (EPP). Plasma concentrations have been evaluated in most pharmacokinetic studies and for therapeutic drug monitoring (TDM), with controversial outcomes. We investigated EPP to evaluate its impact on TRT pharmacokinetics and laboratory assays. METHODS: TRT concentrations were monitored in spiked whole blood, in plasma and erythrocytes separated from spiked whole blood, and in plasma spiked directly. The erythrocyte-plasma partitioning coefficient (Ke/p) was established at 38 °C, room temperature (RT), and 2–8 °C. TRT concentrations and Ke/p were assessed in samples collected from a pediatric patient receiving TRT and in the steady state. Assays were performed using liquid chromatography-mass spectrometry and an in-house method validated for plasma TRT assays. RESULTS: TRT was chemically stable in whole blood and plasma at RT and 2–8 °C. The TRT content of erythrocytes varied by concentration and storage temperature. At 20 ng/mL, Ke/p increased remarkably at RT and 38 °C, but remained unchanged at 2–8 °C. At 60 ng/mL, Ke/p increased throughout the 4-hour time frame, though to a considerably lesser extent. In in vivo samples, Ke/p showed a strong multivariate correlation with time after dose intake and the product of dose and hematocrit at 7.33–15.7 h postdose (r = 0.987). TRT also exerted temperature-dependent diffusion from erythrocytes into TRT-free plasma. CONCLUSIONS: EPP of TRT is related to concentration, temperature, and time in the therapeutic concentration range. Parallel whole blood and plasma TRT assays may therefore be useful for clinical pharmacokinetic studies and TDM. </p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"920-928"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of possible baseline and treatment-course factors associated with non-remission in patients with Crohn's disease treated with ustekinumab: a retrospective real-life analysis.","authors":"Antonio Tursi, Raffaele Pellegrino, Giammarco Mocci, Walter Elisei, Franco Scaldaferri, Edoardo V Savarino, Giovanni Maconi, Giorgia Bodini, Alfredo Papa, Antonietta Gerarda Gravina","doi":"10.1007/s43440-026-00847-5","DOIUrl":"10.1007/s43440-026-00847-5","url":null,"abstract":"<p><p>BACKGROUND: Factors predicting persistent failure to achieve long-term clinical remission with ustekinumab (UST) in Crohn’s disease (CD) are poorly defined, limiting early identification of patients unlikely to benefit from continuation of an ineffective treatment. METHODS: A multicentre retrospective registry was established comprising adult patients with CD treated with UST (induction as per guidelines and maintenance 90 mg every 8 weeks), including clinico-demographic variables and disease activity parameters. These variables were retrospectively collected at baseline (T0) and at 2 (T1), 3 (T2), 6 (T3) and 12 (T4) months. The primary endpoint was the identification of factors associated with failure to achieve clinical remission (defined as an HBI ≥ 5) at T3, with the same assessment performed at T4 as a secondary endpoint. RESULTS: A total of 254 patients were included in the T3 analysis and 143 in the T4 analysis. At T3, lack of remission was associated with prior exposure to 5-ASA (aOR 2.704, 95%CI 1.423–5.137), appendectomy (aOR 1.965, 95%CI 1.008–3.829) and CD diagnosis before the age of 40 (aOR 2.03, 95%CI 1.072–3.834). At T4, appendectomy confirmed the association (aOR 2.938, 95%CI 1.212–7.124). A baseline FC cut-off ≥ 250 µg/g predicted lack of remission at six months (aOR 3.57, 95%CI 1.686–7.561). CONCLUSION: Several anamnestic and on-treatment variables warrant evaluation in this setting, pending confirmation in larger datasets. </p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"891-901"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sigma receptor ligands in selected affective disorders, psychoses, and addictions - a narrative review.","authors":"Agnieszka Piechal, Alicja Jakimiuk, Justyna Pyrzanowska","doi":"10.1007/s43440-026-00852-8","DOIUrl":"10.1007/s43440-026-00852-8","url":null,"abstract":"<p><p>Sigma receptors (SRs), comprising the sigma 1 (S1R) and sigma 2 (S2R) subtypes, represent a distinct class of intracellular proteins that differ fundamentally from classical neurotransmitter receptors. S1Rs act as ligand-operated molecular chaperones primarily localized at mitochondria-associated membranes (MAM) of the endoplasmic reticulum (ER), whereas S2Rs, identified as transmembrane protein 97 (TMEM97), function as modulators of cellular homeostasis. Both subtypes are densely expressed in brain regions critical for emotional and cognitive processing, including the prefrontal cortex (PFC), hippocampus (HIP), amygdala (AMG), and basal ganglia. SRs play a pivotal role in regulating neuronal excitability, synaptic plasticity, and ER stress responses, thereby influencing oxidative stress, synaptogenesis, and neuronal survival. Moreover, their interactions with endogenous neurosteroids and the immune-endocrine system highlight their involvement in complex neuropsychiatric pathophysiology. Consequently, SRs are increasingly recognized as promising targets for pharmacological intervention. Preclinical evidence indicates that S1R agonists exert antidepressant, anxiolytic, and pro-cognitive effects, whereas S1R antagonism or genetic deletion induces behavioural phenotypes relevant to depression and schizophrenia. S2R modulation, in turn, influences psychostimulant sensitivity and emotional regulation, although its underlying mechanisms remain less well defined. Notably, the clinical efficacy of several widely used antidepressants (e.g., fluvoxamine) and antipsychotics have been increasingly attributed to their significant affinity for SRs, suggesting that SR engagement may contribute to their therapeutic profiles. This narrative review synthesizes core molecular and neurophysiological findings and critically evaluates the potential of SR-targeting compounds as next-generation pharmacological strategies for treatment-resistant depression, psychotic disorders, and addiction. Given the continuous emergence of new research, this work provides an updated overview of the current state of knowledge for both researchers and clinicians.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"641-665"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a tetrazole-thiourea derivative as a potential active agent against multidrug-resistant Staphylococcus aureus and Mycobacterium tuberculosis.","authors":"Jolanta Szymańska-Majchrzak, Agnieszka Głogowska, Ewa Augustynowicz-Kopeć, Katarzyna Ewa Greber, Krzesimir Ciura, Wioletta Olejarz, Tomasz Szostek, Marta Struga, Daniel Szulczyk","doi":"10.1007/s43440-026-00848-4","DOIUrl":"10.1007/s43440-026-00848-4","url":null,"abstract":"<p><p>BACKGROUND: Rifampicin-resistant Mycobacterium tuberculosis (RR-TB) and methicillin-resistant Staphylococcus aureus (MRSA) underscore the need for new antibacterial chemotypes active across M. tuberculosis M. tuberculosis and Gram-positive pathogens. Both thiourea and tetrazole are well-established scaffolds in the scientific community for their promising antibacterial properties. The combination of tetrazole and thiourea moieties into a single molecular framework presents a promising strategy to overcome antimicrobial resistance. METHODS: We designed and synthesized a series of tetrazole–thiourea derivatives (1–9) and a bis-tetrazole hybrid (10) through a one-step synthetic approach. Their antimicrobial potential was evaluated using a combination of in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, experimental lipophilicity determination (logD), and in vitro antibacterial assays against both reference and multidrug-resistant staphylococcal strains. Additionally, antitubercular activity was assessed against drug-sensitive, multidrug-resistant (MDR), and extensively drug-resistant (XDR) M. tuberculosis isolates. Molecular docking studies were performed to explore the binding interactions of the compounds with dihydrofolate reductase (DHFR) and penicillin-binding protein 4 (PBP4). RESULTS: Compound 2, bearing a trifluoromethyl substituent, was the most potent. It achieved sub-µg/mL minimum inhibitory concentrations (MICs, 0.1–0.5 µg/mL) against staphylococci, comparable to ciprofloxacin, and maintained strong antitubercular activity (MIC = 0.5 µg/mL) across drug-sensitive, MDR, and XDR strains. Docking supported a dual-target mechanism involving DHFR and PBP4, providing a plausible rationale for its broad antibacterial efficacy. Despite higher lipophilicity within the series, compound 2 showed favorable ADMET predictions and experimental logD values in the developable range. CONCLUSIONS: The tetrazole–thiourea scaffold, exemplified by compound 2, delivers dual efficacy against multidrug-resistant staphylococci and M. tuberculosis. These findings position compound 2 as a promising lead and a rational starting point for hit-to-lead optimization focused on potency–permeability balance and experimental confirmation of dual-target engagement. </p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"862-874"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A validated FACS-based protocol for the isolation of neuronal and non-neuronal cells from frozen adult brain, suitable for integrated gene and protein analysis.","authors":"Magdalena Kolasa, Adam Roman, Przemysław Mielczarek, Joanna Solich, Agata Faron-Górecka","doi":"10.1007/s43440-026-00854-6","DOIUrl":"10.1007/s43440-026-00854-6","url":null,"abstract":"<p><p>BACKGROUND: The isolation of intact cell populations from archived tissue is critical for understanding cell-type-specific functions in neuroscience. This study presents a streamlined, bench-ready fluorescence-activated cell sorting (FACS) protocol for the isolation of neuronal and non-neuronal populations from frozen adult rat cortex, specifically optimized for integrated RNA and protein analyses. METHODS: The method employs a gentle enzymatic digestion and mechanical trituration, followed by fixation with zinc salts, which successfully addresses the challenges of dissociating adult brain tissue while preserving key cellular markers. The protocol’s versatility is demonstrated by its compatibility with two distinct collection buffers, enabling the simultaneous preparation of samples for both RNA and protein analysis, performed by qRT-PCR and mass spectrometry, respectively. RESULTS: Neuronal (PE+) and non-neuronal (PE-) fractions were isolated with high purity, as confirmed by significant enrichment of Rbfox3, Map2, and Tubb3 (neuronal) and Gfap, Iba1, Olig2, and Cldn5 (non-neuronal) via qRT-PCR. Subsequent proteomic analysis further confirmed the distinct identities of the sorted populations, with key neuronal and non-neuronal markers showing significant enrichment in their respective fractions. CONCLUSIONS: Despite a conservative yield (ca. 20,000 neurons per sample) prioritized for cellular intactness, the obtained material was sufficient for high-sensitivity qPCR (mRNA/miRNA) and mass spectrometry. This accessible and time-efficient protocol provides a robust platform for parallel RNA and protein analysis of defined brain cell populations from archived frozen tissue. </p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"875-890"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diurnal variation of cisplatin-induced anti-tumor effect and renal toxicity in mice bearing human colon cancer cells.","authors":"Hiroki Yoshioka, Yurie Mikami, Kohei Matsushita, Satoshi Yokota, Shuji Yamashita, Fumina Susaki, Hanane Horita, Hyogo Horiguchi, Tohru Maeda, Nobuhiko Miura","doi":"10.1007/s43440-026-00831-z","DOIUrl":"10.1007/s43440-026-00831-z","url":null,"abstract":"<p><p>BACKGROUND: Cisplatin is a platinum-containing drug widely used to treat various types of cancer, which causes severe side effects, including acute renal toxicity. We previously reported that cisplatin-induced renal toxicity varies with exposure time. Administration timing may impact anticancer drug therapeutic efficacy. Although chronobiology-based approaches have been developed in both pharmacology and toxicology, reports evaluating their efficacy remain sparse. We herein investigated whether diurnal variations in cisplatin-induced anticancer effects and nephrotoxicity exhibit parallel patterns in a xenograft mouse model bearing red-fluorescent human colon cancer cells (HT29-RFP). METHODS: Using a xenograft mouse model bearing HT29-RFP cells, we compared the pharmacological and toxicological effects of cisplatin injection (5 mg/kg, intraperitoneally three times per week) in the dark (zeitgeber time (ZT) 14) or light (ZT2) phase from 2 to 6 weeks. RESULTS: Cisplatin injection during the dark phase (ZT14) resulted in stronger toxicity, including body weight reduction, and elevated plasma dysfunction and acute renal injury markers, compared to light phase (ZT2) administration. We also demonstrated that the anti-cancer potency of cisplatin against HT29-RFP cells was significantly higher with administration at ZT14 than at ZT2. CONCLUSION: These findings suggest that observed cisplatin-induced diurnal variations in toxicological and pharmacological effects follow a similar pattern in a xenograft mouse model bearing HT29-RFP cells. </p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"902-910"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione deficiency in the early postnatal developmental period as a neurodevelopmental animal model of schizophrenia.","authors":"Zofia Rogóż, Agnieszka Wąsik","doi":"10.1007/s43440-026-00853-7","DOIUrl":"10.1007/s43440-026-00853-7","url":null,"abstract":"<p><p>The etiopathology of schizophrenia is still poorly understood. Still, it is widely accepted that oxidative stress, particularly during early stages of brain development, is associated with increased risk of developing schizophrenia. Several studies indicate that glutathione (GSH) is a key factor in maintaining redox balance in cells and is involved in numerous metabolic processes. Its deficiency in the neonatal period leads to permanent brain damage, manifested by schizophrenia-like symptoms in adults. Hence, administration of the GSH synthesis inhibitor L-buthionine-(S, R)-sulfoximine (BSO) alone and in co-treatment with the dopamine reuptake inhibitor 1-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4-3-(3-phenylpropyl) (GBR 12909) to rodents in neonatal period produces good neurodevelopmental models offering an opportunity to examine various neuroanatomical changes and different symptoms in schizophrenia spectrum. Schizophrenia is modeled by inducing lesions or changes in activity in specific brain regions of rodents (primarily the prefrontal cortex and hippocampus). Such artificially induced dysfunctions, discussed in this article, suggest the usefulness of these neurodevelopmental models in research on the pathomechanisms of schizophrenia. The aim of this review is to analyze the literature on the impact of GSH deficiency on the etiopathology of schizophrenia, with particular emphasis on neurodevelopmental animal models in which oxidative stress during early postnatal development causes schizophrenia-like symptoms in adulthood.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"666-678"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in indole-thiazole hybrid scaffolds: synthesis, molecular hybridization, and pharmacological potential.","authors":"Doaa A Abdelrheem, Sally Mostafa Khadrawy, Mohamed A M Ali, Saleh Alkhedhairi, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi, Emadeldin M Kamel","doi":"10.1007/s43440-026-00856-4","DOIUrl":"10.1007/s43440-026-00856-4","url":null,"abstract":"<p><p>Indole-thiazole hybrids have attracted increasing interest in medicinal chemistry in recent years, combining the privileged indole nucleus with the thiazole ring within a single framework. The indole unit offers opportunities for π-π interactions and hydrogen bonding, while the thiazole ring enables tuning of lipophilicity and electronic properties and can support additional heteroatom-mediated interactions. This review summarizes synthetic approaches, structure-activity relationships (SAR), computational studies, and reported biological activities of indole-thiazole hybrids. The discussed applications include anticancer and antimicrobial studies, antidiabetic activity, and selected enzyme inhibition. Emerging directions such as greener multicomponent routes, structure-based design and docking, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) evaluation are highlighted. Finally, key challenges and perspectives for optimizing indole-thiazole hybrids as therapeutic leads are outlined.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"707-730"},"PeriodicalIF":4.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}