Archiv der Pharmazie最新文献_第2页

Thiazolopyrimidine, a privileged scaffold: Recent updates on synthetic and pharmacological perspective in drug discovery

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-24 DOI: 10.1002/ardp.202400870

Rakesh Khator, Vikramdeep Monga

引用次数: 0

Dual inhibition of canonical and noncanonical PAR-1 by SCH79797 mitigates neurodegeneration in 3-NP-induced Huntington's disease: An in vivo and in silico approach

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-24 DOI: 10.1002/ardp.202400846

Raghda T. Abdel-Latif, Hanan S. El-Abhar, Dalaal M. Abdallah, Iten M. Fawzy, Suzan M. Mansour

{"title":"Dual inhibition of canonical and noncanonical PAR-1 by SCH79797 mitigates neurodegeneration in 3-NP-induced Huntington's disease: An in vivo and in silico approach","authors":"Raghda T. Abdel-Latif, Hanan S. El-Abhar, Dalaal M. Abdallah, Iten M. Fawzy, Suzan M. Mansour","doi":"10.1002/ardp.202400846","DOIUrl":"https://doi.org/10.1002/ardp.202400846","url":null,"abstract":"Though abnormal platelet function is detected in Huntington's disease (HD), thrombin's role is indistinct. Through protease-activated receptor 1 (PAR-1) activation, thrombin triggers intricate pathways relevant to HD. Therefore, we propose that posttreatment with the PAR-1 inhibitor SCH79797 may alleviate symptoms in a 3-nitropropionic acid (3-NP) HD model. Wistar rats were administered 3-NP alone or treated with SCH79797. In silico study showed better blood–brain barrier (BBB) diffusion by SCH79797 than by vorapaxar. Docking showed that SCH79797 blocks thrombin/PAR-1 binding and directly inhibits metalloproteinase (MMP)-1. Molecular dynamics confirmed minimal energy deviation and stable interactions with both PAR-1 and MMP-1 and root mean square deviation (RMSD) verified conformational stability. In the in vivo part, behavioral and striatal improvements were observed, with SCH79797 reducing striatal levels of thrombin and MMP-1, and the expression of PAR-1, N-methyl-d-aspartate (NMDA) receptor subunits (1 and 2B), and MMP-9, while increasing that of claudin-5, contributing to BBB integrity. SCH79797 also lowered tumor necrosis factor (TNF)-α and mitofusin (Mfn)-2, rebalanced the redox system by reducing malondialdehyde (MDA) and enhancing superoxide dismutase (SOD), and prevented 3-NP-induced mitophagy via the PTEN-induced kinase (PINK)-1/ubiquitin pathway. SCH79797 inhibited apoptosis, by reducing caspase-3 and cytochrome C, and increased voltage-dependent anion channel-1 (VDAC1) to maintain mitochondrial function. Overall, SCH79797 inhibited PAR-1 canonically and noncanonically to counter excitotoxicity, oxidative stress, inflammation, apoptosis, and mitophagy, thereby preserving BBB and mitochondrial integrity, improving histological outcomes, and enhancing behavioral performance.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690155","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}

引用次数: 0

Biginelli dihydropyrimidines and their acetylated derivatives as L-/T-type calcium channel blockers: Synthesis, enantioseparation, and molecular modeling studies

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-24 DOI: 10.1002/ardp.202400584

Miyase Gözde Gündüz, Cagatay Dengiz, Katrin Denzinger, Sun Huang, J. T. Lee, Jordan W. Nafie, Daniel W. Armstrong, Gerhard Wolber, Gerald W. Zamponi

{"title":"Biginelli dihydropyrimidines and their acetylated derivatives as L-/T-type calcium channel blockers: Synthesis, enantioseparation, and molecular modeling studies","authors":"Miyase Gözde Gündüz, Cagatay Dengiz, Katrin Denzinger, Sun Huang, J. T. Lee, Jordan W. Nafie, Daniel W. Armstrong, Gerhard Wolber, Gerald W. Zamponi","doi":"10.1002/ardp.202400584","DOIUrl":"https://doi.org/10.1002/ardp.202400584","url":null,"abstract":"Biginelli dihydropyrimidines (DHPMs) are considered superior over 1,4-dihydropyridines (DHPs) in terms of both light and metabolic stabilities. Nevertheless, DHPs dominate the market as the most prescribed calcium channel blockers with strong therapeutic potential in managing cardiovascular ailments. To overcome the restrictions that complicate the formulation and postadministration of DHPs, employing bioisosteric replacement by exchanging the DHP ring with DHPM appears as a logical approach for the improved formulations of new calcium channel blockers. In this study, we obtained DHPM derivatives via Biginelli synthesis and acetylated their N-3 position by heating them in acetic anhydride (GD1–GD12). We also incorporated the DHPM scaffold into a condensed ring system (GD13 and GD14). These DHPMs were evaluated for their ability to block both L- (Cav1.2) and T- (Cav3.2) type calcium channels. Compounds carrying acetyl moiety on the N-3 position of the DHPM scaffold appeared to be more effective inhibitors of both channels. Retesting GD4 enantiomers, separated using high-performance liquid chromatography (HPLC) on a chiral stationary phase, revealed that the (R)-isomer predominantly contributes to the outstanding inhibitory activity of GD4 on calcium channels. Molecular modeling studies, including docking, molecular dynamics simulations, and dynophore analysis, provided insights into the binding mechanism of DHPMs to Cav1.2 and Cav3.2, for the first time.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690154","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}

引用次数: 0

A review of recent advances in anticancer activity and SAR of pyrazole derivatives

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-17 DOI: 10.1002/ardp.202400470

Heba A. Hofny, Mamdouh F. A. Mohamed, Heba A. Hassan, El-Shimaa M. N. Abdelhafez, Gamal El-Din A. Abuo-Rahma

{"title":"A review of recent advances in anticancer activity and SAR of pyrazole derivatives","authors":"Heba A. Hofny, Mamdouh F. A. Mohamed, Heba A. Hassan, El-Shimaa M. N. Abdelhafez, Gamal El-Din A. Abuo-Rahma","doi":"10.1002/ardp.202400470","DOIUrl":"https://doi.org/10.1002/ardp.202400470","url":null,"abstract":"The present review serves to highlight the antitumor worth of pyrazole derivatives. Several active pyrazole-based anticancer compounds proposed by a huge number of scientists worldwide are reported. Regarding the development of novel pyrazole-based anticancer agents at a faster tone, there is a need to correlate the latest information with previously available information to understand the situation of this moiety in anticancer drug discovery studies. Herein, different anticancer pyrazoles are classified according to their mode of action at different anticancer targets. The results provided evidence that pyrazole derivatives have potential applications for the treatment of a variety of tumor types. From the study's findings, the structure–activity relationship (SAR) results demonstrated that all the compounds containing substituted pyrazole represent an important scaffold for anticancer activities. Publications in this area are increasing, and therefore, new therapeutic applications involving members of pyrazole derivatives could be discovered in the near future, as many prospects have not been sufficiently studied so far for other targets. In other words, this review provides an overview of the state of knowledge about the structural characteristics of the most recent anticancer pyrazole derivatives and their SAR with various targets. This will allow medicinal chemists to identify promising structures to guide the design and synthesis of more effective and safer anticancer candidates.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633060","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}

引用次数: 0

Silybin loaded Ag-nanoparticles as a drug delivery system for solid tumor theragnosis: Extraction, radioiodination, and biodistribution study

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-17 DOI: 10.1002/ardp.202400725

Basma M. Essa, Islam M. Abdelmonem, Mohamed A. Amin, Adli A. Selim

引用次数: 0

Synthesis and analytical profile of new synthetic analogs of angiotensin 1-7, the main balancing peptide of the renin–angiotensin system

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-17 DOI: 10.1002/ardp.202500093

Petar Todorov, Stela Georgieva, Diana Cheshmedzhieva, Borislav Assenov, Еlena Dzhambazova, Dimo Angelov, Daniela Pechlivanova

{"title":"Synthesis and analytical profile of new synthetic analogs of angiotensin 1-7, the main balancing peptide of the renin–angiotensin system","authors":"Petar Todorov, Stela Georgieva, Diana Cheshmedzhieva, Borislav Assenov, Еlena Dzhambazova, Dimo Angelov, Daniela Pechlivanova","doi":"10.1002/ardp.202500093","DOIUrl":"https://doi.org/10.1002/ardp.202500093","url":null,"abstract":"The heptapeptide angiotensin Asp-Arg-Val-Tyr-Ile-His-Pro (ANG 1-7) is a key member of the ACE2/ANG-(1-7)/MasR axis, which is considered a counter-regulator of the classical renin–angiotensin system (RAS) axis concerning its homeostatic and neuromodulatory functions. Four new analogs of ANG 1-7 with general structures of Asp-Arg-Val-Tyr-Ile-His-Xxx-NH2, where Xxx is 1-aminocyclopentanecarboxylic acid (Ac5c), 1-aminocyclohexane carboxylic acid (Ac6c), and (2S,4S)-4-amino-pyrrolidine-2-carboxylic acid, were synthesized and characterized by electrochemical, spectral, DFT calculational, and behavioral methods. The presence of a cis-oriented primary amino group at the molecule's C-terminus is coupled with the structural rigidity of the pyrrolidine Pro ring in the peptide molecule ANG-P1. While in ANG-P2, the cis-oriented primary amino group is connected to the peptide motif by means of the amino acid His leading to the formation of a proline/GABA cis-chimera. The partition coefficient values suggest better lipophilicity of the compounds ANG-P1 and ANG-P2 related to easier passage through the target membranes. The correlation coefficient between the theoretically predicted and experimentally determined logP values is 0.991. The ANG-P1 analog has features comparable to ANG 1-7, but the peptides ANG-P2, ANG-C5, and ANG-C6 exhibit distinct effects, particularly on anxiety-like behavior, according to a comparison of the novel analogs with the precursor peptide. Regardless of how they affect exploration in the open field test, they induce anxiogenic behavior in the elevated plus maze test. The ANG-C5 analog differs from the other analogs because it is unable to create antinociception, despite the fact that ANG 1-7 and its analogs generated notable antinociception.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633061","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}

引用次数: 0

Recent advances of hyaluronic acid-based materials in drug delivery systems and regenerative medicine: A review

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-17 DOI: 10.1002/ardp.202400903

Mohamed J. Saadh, Hanan Hassan Ahmed, Radhwan Abdul Kareem, Ashok Kumar Bishoyi, R. Roopashree, Debasish Shit, Renu Arya, Kamal Kant Joshi, Hayder Naji Sameer, Ahmed Yaseen, Zainab H. Athab, Mohaned Adil, Asghar Narmani, Bagher Farhood

{"title":"Recent advances of hyaluronic acid-based materials in drug delivery systems and regenerative medicine: A review","authors":"Mohamed J. Saadh, Hanan Hassan Ahmed, Radhwan Abdul Kareem, Ashok Kumar Bishoyi, R. Roopashree, Debasish Shit, Renu Arya, Kamal Kant Joshi, Hayder Naji Sameer, Ahmed Yaseen, Zainab H. Athab, Mohaned Adil, Asghar Narmani, Bagher Farhood","doi":"10.1002/ardp.202400903","DOIUrl":"https://doi.org/10.1002/ardp.202400903","url":null,"abstract":"Nowadays, diseases have a high rate of incidence and mortality worldwide. On the other side, the drawbacks of conventional modalities in the suppression of diseases have encountered serious problematic issues for the health of human beings. For instance, although various approaches have been applied for the treatment of cancer, it has an ever-increasing rate of incidence and mortality throughout the globe. Thus, there is a fundamental requirement for the development of breakthrough technologies in the inhibition of diseases. Hyaluronic acid (HA) is one of the most practical biopolymers in the suppression of diseases. HA has lots of potential physicochemical (like rheological, structural, molecular weight, and ionization, etc.) and biomedical properties (bioavailability, biocompatibility, CD44 targeting and signaling pathways, components of biological organs, mucoadhesion, immunomodulation, etc.), which made it a potential candidate for the development of breakthrough tools in pharmaceutical and biomedical sciences. The ease of surface modification (carboxylation, amidation, hydroxylation, and esterification), high bioavailability and synthesis routes, and various administration routes are considered as other merits of HA-based vehicles. These mucopolysaccharide HA-based materials have been considerably developed for use in drug delivery systems (DDSs), cancer therapy, wound healing, antiaging, and tissue engineering. This review summarizes the advantages of HA-based DDS and scaffolds in the treatment of diseases.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633062","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}

引用次数: 0

Xylazine as an emerging new psychoactive substance; focuses on both 5-HT7 and κ-opioid receptors' molecular interactions and isosteric replacement 赛拉嗪作为一种新兴的精神活性物质；重点研究 5-HT7 和 κ-阿片受体的分子相互作用和同工异构替代作用

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-17 DOI: 10.1002/ardp.202500041

Giuseppe Floresta, Alberto Granzotto, Vincenzo Patamia, Davide Arillotta, Gabriele D. Papanti, Amira Guirguis, John M. Corkery, Giovanni Martinotti, Stefano L. Sensi, Fabrizio Schifano

{"title":"Xylazine as an emerging new psychoactive substance; focuses on both 5-HT7 and κ-opioid receptors' molecular interactions and isosteric replacement","authors":"Giuseppe Floresta, Alberto Granzotto, Vincenzo Patamia, Davide Arillotta, Gabriele D. Papanti, Amira Guirguis, John M. Corkery, Giovanni Martinotti, Stefano L. Sensi, Fabrizio Schifano","doi":"10.1002/ardp.202500041","DOIUrl":"https://doi.org/10.1002/ardp.202500041","url":null,"abstract":"Xylazine, traditionally used as a veterinary sedative, has recently emerged as a new psychoactive substance, being typically ingested in combination with fentanyl derivatives and hence raising significant public health concerns. Despite its increasing prevalence, little is known about its molecular interactions with human neuroreceptors, specifically the serotonin 7 (5-HT7R) and kappa-opioid (KOR) receptors, which play critical roles in mood regulation, consciousness and nociception. Hence, the binding affinity and molecular interactions of xylazine with both 5-HT7R and KOR through docking simulations and molecular dynamics calculations were investigated. These computational approaches revealed critical insights into receptor binding motifs and highlighted structural modifications that could enhance receptor affinity. The isosteric replacements within the xylazine structure to improve its binding efficacy were assessed, demonstrating that minimal structural modifications can potentiate its interaction with 5-HT7R and KOR. These findings may well advance our understanding of xylazine's mechanism of action, possibly contributing to identifying suitable treatment/management approaches in treating xylazine-related overdoses.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202500041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632644","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}

引用次数: 0

The current landscape of 1,2,3-triazole hybrids with anticancer therapeutic potential: Part I

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-13 DOI: 10.1002/ardp.202500001

Shanshan Huang, Zhi Xu, Yafei Zhuang

{"title":"The current landscape of 1,2,3-triazole hybrids with anticancer therapeutic potential: Part I","authors":"Shanshan Huang, Zhi Xu, Yafei Zhuang","doi":"10.1002/ardp.202500001","DOIUrl":"https://doi.org/10.1002/ardp.202500001","url":null,"abstract":"Cancer, with its steadily increasing morbidity and mortality, will continue to pose a threat to humanity over an extended period. Chemotherapeutics play an indispensable role in cancer treatment, and hundreds of drugs have been approved for this purpose. Nevertheless, the fight against cancer remains a formidable challenge. This is mainly due to the emergence of multidrug resistance and the severe side effects associated with currently available anticancer drugs. Consequently, there is an urgent imperative to explore novel chemotherapeutic agents. 1,2,3-Triazoles belong to one of the most privileged classes of nitrogen-containing five-membered heterocycles and are regarded as prominent sources for the development of innovative anticancer chemotherapeutics. 1,2,3-Triazole hybrids, which possess multitargeted mechanisms of action within the cancer progression pathway, hold the potential to overcome multidrug resistance and mitigate side effects. Furthermore, several 1,2,3-triazole hybrids have already been approved for cancer therapy or are currently under clinical evaluation. This clearly demonstrates that 1,2,3-triazole hybrids are valuable scaffolds in the treatment and eradication of cancer. This review aims to provide insights into the anticancer therapeutic potential of 1,2,3-triazole hybrids, along with their mechanisms of action, crucial aspects of design, and structure–activity relationships (SARs). It encompasses articles published from 2021 onward.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602533","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}

引用次数: 0

Research progress of cycloartane triterpenoids and pharmacological activities

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-03-12 DOI: 10.1002/ardp.202400923

Chen Wang, Xiaodong Mu, Jingyong Sun

引用次数: 0