Archiv der Pharmazie最新文献

{"title":"Unraveling the Therapeutic Mechanisms of Aloe-Emodin: A Natural Anthraquinone With Promising Health Benefits.","authors":"Sumaiya Akter Annie, Md Abir Khan, Abdullah Talukder, Ahm Khurshid Alam, Md Josim Uddin","doi":"10.1002/ardp.70247","DOIUrl":"https://doi.org/10.1002/ardp.70247","url":null,"abstract":"<p><p>Aloe-emodin (AE), known as 1,8-dihydroxy-3-hydroxymethyl-anthraquinone, is a naturally occurring anthraquinone that has attracted attention for its diverse pharmacological applications. AE is mainly found in plant species, such as Aloe vera, Rheum palmatum, and Polygonum multiflorum. Accumulating preclinical studies suggest that AE exerts anticancer, antimicrobial, antiviral, antiparasitic, hepatoprotective, neuroprotective, cardioprotective, and anti-inflammatory properties. In particular, its anticancer effects, involving apoptosis induction, oxidative stress inhibition, mitochondrial dysfunction, and inhibition of proliferative and metastatic pathways across multiple cancer cell lines, are especially well-characterized. AE demonstrates promising preclinical results, with a range of effective in vitro doses of 0.05 to 100 µM and in vivo doses of 25-100 mg/kg in animals; however, higher micromolar concentrations have been reported to have cytotoxic and hepatotoxic effects, highlighting AE's translational potential while necessitating further safety evaluation. Simultaneously, proliferative signaling pathways, such as PI3K/Akt/mTOR and MAPK, are widely investigated; some potential signaling pathways, like PIP2 stimulation, which also activates the AKT/mTOR pathway, are still unexplored. AE combats various infectious diseases targeting gram-positive and gram-negative bacteria, influenza A, herpes simplex virus, Japanese encephalitis virus, enterovirus 71, and parasites such as Leishmania. Despite the promising pharmacological effects of AE, its clinical application is limited by poor pharmacokinetics, such as low bioavailability, rapid clearance, and inadequate intestinal absorption, along with safety risks like liver, kidney, and light-induced toxicity. Overcoming these challenges require improved delivery systems, structural modifications, and detailed toxicity profiling. Our review consolidates current pharmacological evidence, identifies research gaps, and suggests modifications and future directions for AE as a potential therapeutic agent.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 5","pages":"e70247"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758071","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":"Current Landscape of Indole Hybrids in the Design and Development of Anti-Alzheimer Agents: Structural Insights, Therapeutic Potential and In Silico Studies.","authors":"Akshad D Bagul, Mohd Irfan, Aashish Jaitak, Vivek Asati, Kamya Goyal, Vikramdeep Monga","doi":"10.1002/ardp.70248","DOIUrl":"https://doi.org/10.1002/ardp.70248","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is an irreversible neurodegenerative disorder characterised by progressive cognitive decline, neuronal loss and accumulation of β-amyloid plaques and neurofibrillary tangles. Even after many years of intensive research, scientists still have not found a cure for AD. The current medications can only help to manage the symptoms of AD or slow down the disease progression. This highlights an urgent and unmet need for the development of novel therapeutic agents capable of simultaneously modulating the multifactorial pathological pathways that drive the onset and progression of AD. The multitarget-directed ligand approach has garnered considerable attention in this context, aiming to simultaneously modulate multiple disease-relevant targets, including AChE, BChE, MAO-A and MAO-B, BACE1, and oxidative stress mediators. Indole, a fortunate heterocyclic scaffold, has become a valuable tool for the design and development of multi-target directed ligands in anti-Alzheimer drug discovery due to its favourable physicochemical properties, BBB permeability and medicinal attributes. This review summarises recent advancements in the medicinal chemistry of indole hybrids as anti-Alzheimer agents, highlighting the impact of structural modifications on biological activity, including the underlying molecular mechanisms, structure-activity relationships, and computational studies. The findings summarised in the article can pave the way for future anti-Alzheimer drug discovery.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 5","pages":"e70248"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831249","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":"Correction to \"Effects of Supramolecular Interactions on E/Z-Isomerizations in Water and Their Importance for Biological Applications\".","authors":"","doi":"10.1002/ardp.70253","DOIUrl":"https://doi.org/10.1002/ardp.70253","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 5","pages":"e70253"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831271","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":"Itopride as a Potential Drug Against Cancer (Breast and Prostate), by Repurposing Determined Through AI.","authors":"José Luis Vique-Sánchez, Ana Brenda Ortega Morales","doi":"10.1002/ardp.70252","DOIUrl":"https://doi.org/10.1002/ardp.70252","url":null,"abstract":"<p><p>Breast and prostate cancer continue with high prevalence inside the top five. According to the global cancer statistics published by the American Cancer Society (2022), with approximately 20 million new cancer cases and almost 10 million related deaths each year, the need for more therapeutic options against cancer is evident. Therefore, proposing or repurposing drugs that can contribute to current treatments will be relevant in the healthcare sector. In recent years, following the COVID-19 pandemic, drug repurposing has increased, further amplified by the use of artificial intelligence (AI). In this way, using AI, we propose the drug Itopride as a potential antiproliferative agent in cancer. This effect was determined through in silico and in vitro assays. Therefore, through AI and drug repurposing, we propose Itopride as a potential adjuvant against prostate and breast cancer. This is justified by the cytotoxic and antiproliferative effects of Itopride observed in vitro cultures. Currently, Itopride is available in several countries and is primarily used as a prokinetic agent and for functional dyspepsia.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 5","pages":"e70252"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831311","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":"A Review on Medicinal Chemistry and Biological Activity of Dihydropyrimidinones Against HIV","authors":"Debora I. Leite,&nbsp;Fernando B. Macedo,&nbsp;Murilo Marinho de C. Lima,&nbsp;Isabelle S. Brum,&nbsp;Jonathan Fragoso Miranda de Oliveira,&nbsp;Ana Clara S. Costa,&nbsp;Stella C. Duarte,&nbsp;Sarah Moon,&nbsp;Stefany de Castro B. Moura,&nbsp;Andressa P. de Oliveira,&nbsp;Nubia Boechat,&nbsp;Monica M. Bastos","doi":"10.1002/ardp.70238","DOIUrl":"10.1002/ardp.70238","url":null,"abstract":"<p>Dihydropyrimidinones (DHPMs), also referred to as pyrimidinones, are privileged structures widely employed in the search for new compounds capable of inhibiting HIV replication. This core is found in natural alkaloids isolated from marine sponge species, which are known to inhibit the binding of the viral surface protein gp120 to the CD4 receptor of target cells. In addition, DHPMs exhibit a close structural relationship with nucleic acids, macromolecules that constitute the genetic material of both living organisms and viruses. Furthermore, the DHPM nucleus is present in several important anti-HIV drugs that inhibit reverse transcriptase and integrase enzymes, indicating that the use of these privileged structures represents a faster and more promising approach for the development of novel HIV inhibitors. In this review, we provide an overview of DHPM-based compounds as potential future trends in AIDS treatment, with a focus on studies published over the last 10 years. Overall, our analysis indicates that compounds containing the DHPM core generally display high potency against multiple HIV targets and may overcome antiviral resistance, reinforcing the relevance of this pharmacophoric fragment for the development of effective and innovative antiretroviral therapies.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653413","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":"Xanthenone Orchestrates the Renin–Angiotensin System/Ferroptosis Crosstalk: A Novel AT2R-Dependent Strategy Against Lower Limb Transient Ischemia-Induced Liver Injury","authors":"Miar M. Sherif,&nbsp;Dalaal M. Abdallah,&nbsp;Iten M. Fawzy,&nbsp;Hanan S. El-Abhar","doi":"10.1002/ardp.70236","DOIUrl":"10.1002/ardp.70236","url":null,"abstract":"<div>\u0000 \u0000 <p>Lower limb transient ischemia (LLTI)-induced hepatic injury is intricately linked to redox disequilibrium, inflammation, and emerging modalities of regulated cell death, including ferroptosis. The renin–angiotensin system (RAS), particularly its non-canonical arm, has been implicated in tissue protection, yet its crosstalk with ferroptosis remains underexplored. This study investigated the hepato-therapeutic potential of xanthenone (XNT), an ACE2 activator, in a LLTI-induced liver injury model, with a focus on the Ang-(1–9)/AT2R axis and ferroptosis regulation. Accordingly, male Wistar rats were subjected to LLTI and treated with XNT, with or without the AT2R antagonist PD123319. Hepatic function, oxidative stress markers, ferroptotic signals, and RAS components were assessed using molecular modeling, biochemical, and histopathological techniques. XNT improved liver architecture and reduced ALT/AST levels to confer hepatoprotection. Mechanistically, XNT shifted RAS signaling to the protective ACE2/Ang-(1–9)/AT2R pathway, leading to suppression of Ang-II and enhancement of Ang-I/Ang-(1–9) contents. This shift activated the AKT/Nrf2/HO-1 antioxidant cascade and restored homeostasis of the central anti-ferroptotic system SLC7A11/GSH/GPX4, inhibited ACSL4 expression, thereby reducing ROS, and lipid peroxidation. Importantly, XNT also mitigated ferroptosis by downregulating Fe³⁺/TfR1, Fe²⁺, and ferritin accumulation, while modulating the ferritinophagy axis through upregulation of HERC2 and suppression of NCOA4. These effects were largely abolished by PD123319, indicating AT2R dependency. In conclusion, XNT protects against LLTI-induced hepatic injury by orchestrating a dual antioxidant and anti-ferroptotic response via the Ang-(1–9)/AT2R axis. These findings unveil a novel crosstalk between RAS modulation and ferroptosis regulation, positioning AT2R activation as a promising therapeutic strategy for ischemia/reperfusion-related liver damage.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653436","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":"Synthesis and Characterization of Sulfonamide-Schiff Bases, and Investigation of Cytotoxic, Antioxidant, HDAC, and Apoptotic Activities in Human Colon Cancer Cells (DLD-1 and HT-29)","authors":"Seda Mesci,&nbsp;Berna Kocaman,&nbsp;Aliye Gediz Erturk,&nbsp;Emine Bagdatli,&nbsp;Burak Yazgan,&nbsp;Tuba Yildirim","doi":"10.1002/ardp.70235","DOIUrl":"10.1002/ardp.70235","url":null,"abstract":"<p>Comprehending the intricate mechanisms of apoptosis and its interaction with cytotoxic, antioxidant, and HDAC activities is imperative for devising effective cancer therapies. Sulfonamides and Schiff bases are compounds of pharmacological importance with known anticancer activity. Our study aimed to investigate the cytotoxic, antioxidant, HDAC, and apoptotic activities of new sulfonamide-Schiff bases in human colon cancer cells (DLD-1 and HT-29). New sulfonamide-derived Schiff base compounds (<b>3a</b>–<b>d</b>) were synthesized from the condensation of sulfamethoxypyridazine (<b>1</b>) and various aromatic aldehydes, and were characterized by FTIR, NMR (¹H and ¹³C/APT), UV-Vis., and mass spectroscopy. Sulfonamide-derived Schiff bases <b>3a–d</b> and compound <b>1</b> exhibited significant anticancer activity against colorectal cancer cell lines (DLD-1, HT-29). In the MTT assay, <b>3c</b> was most active in DLD-1 (viability: 37.7%, IC₅₀ = 3.94 µM) and <b>3b</b> in HT-29 (viability: 46.6%, IC₅₀ = 3.26 µM). In the WST-8 assay, <b>3c</b> was strongest in DLD-1 (viability: 45.9%, IC₅₀ = 17.95 µM). None of the compounds showed toxicity in normal colon cells (CCD-18Co). qRT-PCR revealed upregulation of apoptotic (BAX, p53, Caspase-3/8/9) and antioxidant (SOD-1/2, CAT, GSS) genes, notably by <b>3a</b> in DLD-1 and <b>3d</b> in HT-29, while <b>3c</b> reduced BCL-2 in HT-29 cells. ELISA confirmed strong antioxidant induction (<b>3a</b>: 70% in DLD-1) and HDAC inhibition (<b>3d</b>: 69% in HT-29). Western blot showed <b>3a</b> increased p38/MAPK expression sevenfold in DLD-1 and fourfold in HT-29, while decreasing ERK1. Overall, <b>3c</b> and <b>3d</b> emerged as the most promising candidates, combining cytotoxic, antioxidant, HDAC inhibitory, and apoptotic effects, and may act as selective therapeutic agents by targeting the p38/MAPK–ERK1 pathway in colorectal cancer.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13068298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653400","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":"Novel 4-((Benzimidazol-2-yl)methyl)-resorcinol Derivatives as Potential Hsp90 Inhibitors: Synthesis and Initial Inhibition Evaluation","authors":"Vilius Petraška,&nbsp;Gabija Griškonytė,&nbsp;Lukas Neverdauskas,&nbsp;Marius Gedgaudas,&nbsp;Algirdas Brukštus,&nbsp;Egidijus Kazlauskas,&nbsp;Ieva Žutautė","doi":"10.1002/ardp.70232","DOIUrl":"10.1002/ardp.70232","url":null,"abstract":"<div>\u0000 \u0000 <p>Human Hsp90 is a well-established target for cancer treatment, also showing promise for managing certain neurological disorders and infections. This study presents an efficient synthesis of Hsp90 inhibitors featuring resorcinol and benzimidazole moieties connected by a methylene bridge. The reaction time was significantly reduced by using microwave irradiation instead of conventional heating, addressing the instability of 4-[(benzimidazol-2-yl)methyl]-6-benzylresorcinols at higher temperatures. For the comparison, directly connected resorcinol-benzimidazole compounds were synthesized, resulting in 25 desirable compounds. The synthesized compounds were assessed for their binding affinity to human Hsp90. The results indicated a preference for the alpha isoform over the beta isoform. Only the compounds that included a linker between the benzimidazole and resorcinol moieties showed positive results. Among these, compounds without substituents on the benzimidazole and those containing fluorine exhibited the strongest binding affinity. Overall, the findings suggest that the molecular structure plays a crucial role in binding affinity, and expanding the variety of substituents on the molecular framework may enhance the specificity and affinity of Hsp90 inhibitors.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637315","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":"Development and Synthesis of Bioactive (3-Arylediene-1-phenyl-1H-pyrazol-4-yl)acryloyl-4-hydroxy-6-methyl-2H-pyran-2-ones With Anti-Malarial and Anti-Inflammatory Activities","authors":"Priyanka Rani,&nbsp;Sudeep Dhillon,&nbsp;Ginna Kumari,&nbsp;Mamta Chahal,&nbsp;Binesh Kumar,&nbsp;Jai Devi,&nbsp;Deepak Kumar Aneja,&nbsp;Mayank Kinger","doi":"10.1002/ardp.70231","DOIUrl":"10.1002/ardp.70231","url":null,"abstract":"<div>\u0000 \u0000 <p>Chalcones are versatile scaffolds with broad pharmacological relevance, particularly as anti-inflammatory and anti-malarial agents. In the current investigation, a series of (3-arylediene-1-phenyl-1<i>H</i>-pyrazol-4-yl)acryloyl-4-hydroxy-6-methyl-2<i>H</i>-pyran-2-one analogs/1,3-diarylprop-2-en-1-ones were successfully synthesized, leveraging dehydroacetic acid (DHA) as the precursor molecule. The choice of DHA is strategic as it is a bioactive and highly versatile scaffold bearing a 4-hydroxy-6-methyl-2<i>H</i>-pyran-2-one moiety, which enhances structural diversity and provides multiple reactive sites for functionalization. Its inherent anti-microbial, anti-inflammatory, and anti-malarial potential offers an added advantage over conventional precursors, thereby increasing the likelihood of generating pharmacologically active chalcone hybrids. The synthetic protocol employed in this study involved the implementation of a Claisen condensation reaction, wherein DHA was reacted with formyl pyrazole to afford the corresponding chalcones, with yields ranging from moderate to good. The synthesized compounds were subjected to a rigorous characterization protocol, involving a battery of analytical techniques, including ¹H-NMR, ¹³C-NMR, FT-IR, and HRMS analyses. Biological evaluation focused on anti-malarial and anti-inflammatory activities, while molecular docking (PyRx 0.8) was performed to explore binding interactions with cyclooxygenase-2 (COX-2; PDB ID: 3LN1) and enoyl-acyl-carrier-protein reductase (EACPR; PDB ID: 1NHG). Notably, compound <b>3c</b> emerged as the most potent one within the synthesized series, exhibiting remarkable anti-inflammatory and anti-malarial potency, as evidenced by its IC₅₀ values of 7.05 ± 0.17 µM and 0.95 ± 0.06 µM, respectively. Docking studies revealed strong binding affinities and favorable molecular interactions, supporting the observed bioactivities. This study highlights chalcone–pyrazole hybrids as promising therapeutic scaffolds. In particular, compound <b>3c</b> emerges as a compelling lead candidate for further optimization and preclinical investigation as a dual-action agent against malaria and inflammation.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637340","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":"Issue Information: Arch Pharm (4/2026)","authors":"","doi":"10.1002/ardp.70237","DOIUrl":"https://doi.org/10.1002/ardp.70237","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"359 4","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147686849","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}