Archiv der Pharmazie最新文献_第6页

2-Phenylbenzothiazoles featuring heteroaryl sulfonamide end-capping substructures as developable mPGES-1 inhibitors 具有杂芳基磺酰胺端盖亚结构的2-苯基苯并噻唑作为可开发的mPGES-1抑制剂。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-16 DOI: 10.1002/ardp.202400756

Tansu Yalçın, Paul M. Jordan, Abdurrahman Olğaç, Philipp Dahlke, Tuğçe Gür Maz, Erden Banoglu, Oliver Werz, Burcu Çalışkan

引用次数: 0

Design, synthesis, and evaluation of dehydroabietyl imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones as TDP1 inhibitors and dual TDP1/TDP2 inhibitors 脱氢枞基咪唑烷-2,4-二酮、2,4,5-三酮和2-硫氧咪唑烷-4,5-二酮作为TDP1抑制剂和双TDP1/TDP2抑制剂的设计、合成和评价

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-13 DOI: 10.1002/ardp.202400801

Kseniya S. Kovaleva, Olga I. Yarovaya, Yuriy V. Gatilov, Anastasiya V. Lastovka, Irina A. Chernyshova, Nadezhda S. Dyrkheeva, Arina A. Chepanova, Olga I. Lavrik, Nariman F. Salakhutdinov

{"title":"Design, synthesis, and evaluation of dehydroabietyl imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones as TDP1 inhibitors and dual TDP1/TDP2 inhibitors","authors":"Kseniya S. Kovaleva, Olga I. Yarovaya, Yuriy V. Gatilov, Anastasiya V. Lastovka, Irina A. Chernyshova, Nadezhda S. Dyrkheeva, Arina A. Chepanova, Olga I. Lavrik, Nariman F. Salakhutdinov","doi":"10.1002/ardp.202400801","DOIUrl":"10.1002/ardp.202400801","url":null,"abstract":"Tyrosyl DNA phosphodiesterases 1 and 2 (TDP1 and TDP2), which are enzymes involved in the repair of DNA, are regarded as promising targets for the development of new anticancer drugs. In this study, a series of imidazolidine-2,4-diones, 2,4,5-triones, and 2-thioxoimidazolidine-4,5-diones based on dehydroabietylamine (DHAAm) were synthesized. The inhibitory activity of the new compounds against TDP1 and TDP2, as well as their cytotoxic characteristics, were evaluated. All types of heterocyclic DHAAm derivatives demonstrated effective inhibition of TDP1 in the micromolar range, with IC50 values in the range of 0.63–4.95 µM. It was observed that only the 2-thioxoimidazolidine-4,5-diones were TDP2 inhibitors, representing the first class of dual TDP1/TDP2 inhibitors among DHAAm derivatives. The findings of this study may contribute to an enhanced comprehension of the subsequent design of novel dual TDP1/TDP2 inhibitors for the further development of new antitumor agents.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968788","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

The discovery of a new nonbile acid modulator of Takeda G protein-coupled receptor 5: An integrated computational approach 武田G蛋白偶联受体5的一种新的非胆汁酸调节剂的发现：一种综合计算方法。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-13 DOI: 10.1002/ardp.202400423

Rudy Salam, Michael Bakker, Mária Krutáková, Alžbeta Štefela, Petr Pávek, Jurjen Duintjer Tebbens, Jan Zitko

{"title":"The discovery of a new nonbile acid modulator of Takeda G protein-coupled receptor 5: An integrated computational approach","authors":"Rudy Salam, Michael Bakker, Mária Krutáková, Alžbeta Štefela, Petr Pávek, Jurjen Duintjer Tebbens, Jan Zitko","doi":"10.1002/ardp.202400423","DOIUrl":"10.1002/ardp.202400423","url":null,"abstract":"The Takeda G protein-coupled receptor 5 (TGR5), also known as GPBAR1 (G protein-coupled bile acid receptor), is a membrane-type bile acid receptor that regulates blood glucose levels and energy expenditure. These essential functions make TGR5 a promising target for the treatment of type 2 diabetes and metabolic disorders. Currently, most research on developing TGR5 agonists focuses on modifying the structure of bile acids, which are the endogenous ligands of TGR5. However, TGR5 agonists with nonsteroidal structures have not been widely explored. This study aimed at discovering new TGR5 agonists using bile acid derivatives as a basis for a computational approach. We applied a combination of pharmacophore-based, molecular docking, and molecular dynamic (MD) simulation to identify potential compounds as new TGR5 agonists. Through pharmacophore screening and molecular docking, we identified 41 candidate compounds. From these, five candidates were selected based on criteria including pharmacophore features, a docking score of less than 9.2 kcal/mol, and similarity in essential interaction patterns with a reference ligand. Biological assays of the five hits confirmed that Hit-3 activates TGR5 similarly to the bile acid control. This was supported by MD simulation results, which indicated that a hydrogen bond interaction with Tyr240 is involved in TGR5 activation. Hit-3 (CSC089939231) represents a new nonsteroidal lead that can be further optimized to design potent TGR5 agonists.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968792","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

Antioxidant activity, phytochemical composition, and antitumor capacity of Amazonian fruits taperebá (Spondias mombin) and murici (Byrsonima crassifolia)

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-06 DOI: 10.1002/ardp.202400758

Thuane Passos Barbosa Lima, Pedro Paulo Saldanha Coimbra, Ananda da Silva Antonio, Henrique Marcelo Gualberto Pereira, Giovana Ramalho Patrizi da Silva, Valdir Florêncio da Veiga-Junior, Otniel Freitas Silva, Israel Felzenszwalb, Carlos Fernando Araujo-Lima, Anderson Junger Teodoro

{"title":"Antioxidant activity, phytochemical composition, and antitumor capacity of Amazonian fruits taperebá (Spondias mombin) and murici (Byrsonima crassifolia)","authors":"Thuane Passos Barbosa Lima, Pedro Paulo Saldanha Coimbra, Ananda da Silva Antonio, Henrique Marcelo Gualberto Pereira, Giovana Ramalho Patrizi da Silva, Valdir Florêncio da Veiga-Junior, Otniel Freitas Silva, Israel Felzenszwalb, Carlos Fernando Araujo-Lima, Anderson Junger Teodoro","doi":"10.1002/ardp.202400758","DOIUrl":"https://doi.org/10.1002/ardp.202400758","url":null,"abstract":"The Amazon rainforest is renowned for its biodiversity and as a reservoir of edible and medicinal plants. The phytochemicals in murici and taperebá fruits serve as natural antioxidants, contributing to cultural preservation, ecosystem protection, and economic opportunities. However, limited scientific research on their composition and health benefits hinders their recognition as functional foods. This study aimed to evaluate the antioxidant activity, carotenoid content, phenolic compounds, and antitumor effects of murici and taperebá fruit pulps. Four antioxidant tests (2,2-Diphenyl-1-picrylhydrazylradical scavenging activity, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) method, 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) method, oxygen radical absorbance capacity) were conducted, and total phenolics were quantified (Folin-Ciocalteu). Phenolics were identified using UHPLC-HRMS, and carotenoids by high-performance liquid chromatography (HPLC). The impact on breast cancer cell viability (MCF-7, MDA-MB-231) was assessed via water-soluble tetrazolium (WST) assay. Both fruits showed high antioxidant activity and phenolic content, with murici leading. HPLC revealed five carotenoids per fruit, with taperebá showing higher concentrations. UHPLC-HRMS identified 23 phenolic compounds: 16 in murici aqueous extract, 18 in murici ethanolic extract, and 15 in each taperebá extract. WST assay demonstrated that both fruits exerted a significant impact on breast cancer cells, reducing their viability in a dose-dependent manner. These findings underscore the potential of murici and taperebá as sources of phytochemical antioxidants and antiproliferative agents with promising health applications.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143112551","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

Unprecedented carbonic anhydrase inhibition mechanism: Targeting histidine 64 side chain through a halogen bond 前所未有的碳酸酐酶抑制机制：通过卤素键靶向组氨酸64侧链。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-01-06 DOI: 10.1002/ardp.202400776

Roberto Paciotti, Simone Carradori, Andrea Angeli, Ilaria D'Agostino, Marta Ferraroni, Cecilia Coletti, Claudiu T. Supuran

{"title":"Unprecedented carbonic anhydrase inhibition mechanism: Targeting histidine 64 side chain through a halogen bond","authors":"Roberto Paciotti, Simone Carradori, Andrea Angeli, Ilaria D'Agostino, Marta Ferraroni, Cecilia Coletti, Claudiu T. Supuran","doi":"10.1002/ardp.202400776","DOIUrl":"10.1002/ardp.202400776","url":null,"abstract":"2,2′-Thio-bis(4,6-dichlorophenol), namely bithionol, is a small molecule endowed with a multifaceted bioactivity. Its peculiar polychlorinated phenolic structure makes it a suitable candidate to explore its potentialities in establishing interaction patterns with enzymes of MedChem interest, such as the human carbonic anhydrase (hCA) metalloenzymes. Herein, bithionol was tested on a panel of specific hCAs through the stopped-flow technique, showing a promising micromolar inhibitory activity for the hCA II isoform. X-ray crystallographic studies revealed an unprecedented halogen-bond interaction between one chlorine of bithionol and the N3(ε) atom of the hCA II catalytically active histidine residue, His64. Then, quantum mechanics calculations based on the fragment molecular orbital method allowed us to estimate the strength of this bond (~2.9 kcal/mol) and highlighted the contribution of a rich hydrophobic interaction network within the isoenzyme. Interestingly, the compound inactivity against the hCA III isoform, characterized by His64Lys and Leu198Phe mutations, supported the key role played by halogen bonding in the enzyme affinity. This finding might pave the way for the development of a new class of hCA inhibitors characterized by such chemical features, with the halogen bond being a key ligand–receptor interaction.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941775","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

Piperazine-based P2X4 receptor antagonists 哌嗪类P2X4受体拮抗剂。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2024-12-30 DOI: 10.1002/ardp.202400860

Katharina Sophie Erlitz, Alena I. Siutkina, Ann-Kathrin Prinz, Oliver Koch, Dmitrii V. Kalinin, Anna Junker

{"title":"Piperazine-based P2X4 receptor antagonists","authors":"Katharina Sophie Erlitz, Alena I. Siutkina, Ann-Kathrin Prinz, Oliver Koch, Dmitrii V. Kalinin, Anna Junker","doi":"10.1002/ardp.202400860","DOIUrl":"10.1002/ardp.202400860","url":null,"abstract":"The P2X4 receptor (P2X4R), a ligand-gated ion channel activated by ATP, plays a critical role in neuroinflammation, chronic pain, and cancer progression, making it a promising therapeutic target. In this study, we explored the design and synthesis of piperazine-based P2X4R antagonists, building on the structural framework of paroxetine. A series of over 35 compounds were synthesized to investigate structure–activity relationships (SARs) in a Ca²⁺-flux assay for P2X4R antagonistic activity. Several compounds outperformed paroxetine in terms of antagonistic P2X4R potency. Further studies on absorption, distribution, metabolism, excretion properties revealed that increased lipophilicity often correlated with high plasma protein binding and decreased metabolic stability, particularly in compounds with a naphthalene-2-yloxy group. Although promising SARs were observed, further optimization is needed to enhance antagonistic P2X4R receptor activity. This work provides important insights into the development of piperazine-based P2X4R antagonists and lays the foundation for future therapeutic advancements targeting P2X4R-related diseases.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11686045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906463","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-(fused) six-membered nitrogen-containing heteroaromatic ring hybrids with anticancer therapeutic potential 具有抗癌治疗潜力的1,2,3-三唑-（融合）六元含氮杂环杂环化合物的现状。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2024-12-30 DOI: 10.1002/ardp.202400873

Zhi Xu, Rongqiang Li, Zhiwei Huang, Yafei Zhuang

{"title":"The current landscape of 1,2,3-triazole-(fused) six-membered nitrogen-containing heteroaromatic ring hybrids with anticancer therapeutic potential","authors":"Zhi Xu, Rongqiang Li, Zhiwei Huang, Yafei Zhuang","doi":"10.1002/ardp.202400873","DOIUrl":"10.1002/ardp.202400873","url":null,"abstract":"Cancer, characterized by uncontrolled growth and spread of abnormal cells potentially influencing almost all tissues in the body, is one of the most devastating and lethal diseases throughout the world. Chemotherapy is one of the principal approaches for cancer treatment, but multidrug resistance and severe side effects represent the main barriers to the success of therapy, creating a vital need to develop novel chemotherapeutic agents. The 1,2,3-triazole moiety can be conveniently constructed by “click chemistry” and could exert diverse noncovalent interactions with various enzymes in cancer cells. Hence, 1,2,3-triazole is one of the most fascinating anticancer pharmacophores. Moreover, 1,2,3-triazole could also serve as a powerful ligation tool for the complex molecular architectures to increase the anticancer efficacy of lead molecules. Notably, 1,2,3-triazole-containing hybrids with intriguing structural variations could target different biological components in cancer cells simultaneously, highlighting their potential in the treatment and eradication of cancer. This review outlines the current landscape of 1,2,3-triazole-(fused) six-membered nitrogen-containing heteroaromatic ring hybrids, inclusive of 1,2,3-triazole-quinazolines, 1,2,3-triazole-quinazolinones, 1,2,3-triazole-quinolines, 1,2,3-triazole-quinolones, 1,2,3-triazole-pyridines, and 1,2,3-triazole-pyrimidines, with anticancer therapeutic potential, and explores their mechanisms of action, critical aspects of design as well as structure–activity relationships (SARs), covering articles published from 2021 to the present, to pave the way for the development of innovative and efficient therapeutic interventions for cancer therapy.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906464","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

Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure–activity relationship 脱氧水杨苷酮杂交体治疗阿尔茨海默病：人造衍生物、药理活性和构效关系的最新进展

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2024-12-27 DOI: 10.1002/ardp.202400742

Ankur Gaur, Yash Pal Singh, Rajiv Sharma, Neeraj Bainsal

{"title":"Deoxyvasicinone hybrids in the management of Alzheimer's disease: Recent advances on manmade derivatives, pharmacological activities, and structure–activity relationship","authors":"Ankur Gaur, Yash Pal Singh, Rajiv Sharma, Neeraj Bainsal","doi":"10.1002/ardp.202400742","DOIUrl":"10.1002/ardp.202400742","url":null,"abstract":"Alzheimer's disease (AD) is a prevalent neurological illness that affects over 80% of aged adults globally in cases of dementia. Although the exact pathophysiological causes of AD remain unclear, its pathogenesis is primarily driven by several distinct biochemical alterations: (i) the accumulation of toxic Aβ plaques, (ii) the hyperphosphorylation of tau proteins, (iii) oxidative stress resulting in cell death, and (iv) an imbalance between the two main neurotransmitters, glutamate and acetylcholine (ACh). Currently, there are very few medications available and no treatment. Presently marketed medications include memantine, an N-methyl-d-aspartate receptor (NMDA) antagonist, and acetylcholinesterase (AChE) inhibitors: rivastigmine, donepezil, and galantamine. Unfortunately, these medications are only useful in the initial stages of AD. The mentioned medications only provide symptomatic relief and do not slow down the disease progression in the advanced stages. Therefore, there is an urgent need to develop potential candidates to treat AD, symptomatically and therapeutically. Many research groups focus on natural products due to their diverse therapeutic profiles and easy availability. One such natural product is deoxyvasicinone, isolated from Adhatoda vasica. Given its broad pharmacological profile, various researchers have developed semisynthetic hybrids of deoxyvasicinone to address multifaceted diseases like AD. In this review article, we tried to summarize the semisynthetic hybrids of deoxyvasicinone developed over the past decade (2014–2024) for managing AD. We focus on their design, pharmacological activity, and structure–activity relationship (SAR) analysis. We hope this review enhances the reader's understanding of future exploratory options for deoxyvasicinone hybrids in AD management.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890653","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

Curcumin and doxorubicin encapsulated in biocompatible clay-based nanomaterial: A strategy to overcome multidrug resistance 姜黄素和阿霉素包裹在生物相容性粘土基纳米材料中：一种克服多药耐药的策略。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2024-12-26 DOI: 10.1002/ardp.202400702

Paola Poma, Marina Massaro, Salvatrice Rigogliuso, Lucia Condorelli, Rita Sánchez-Espejo, César Viseras, Monica Notarbartolo, Serena Riela

{"title":"Curcumin and doxorubicin encapsulated in biocompatible clay-based nanomaterial: A strategy to overcome multidrug resistance","authors":"Paola Poma, Marina Massaro, Salvatrice Rigogliuso, Lucia Condorelli, Rita Sánchez-Espejo, César Viseras, Monica Notarbartolo, Serena Riela","doi":"10.1002/ardp.202400702","DOIUrl":"10.1002/ardp.202400702","url":null,"abstract":"Multidrug resistance (MDR) due to the overexpression of the P-glycoprotein (P-gp) efflux pump remains a significant challenge in cancer therapy, also in breast cancer. Traditional pharmacological approaches have focused on using inhibitors to modulate P-gp expression and function. Curcumin, a polyphenol derived from Curcuma longa L., is one of the most extensively studied natural compounds with the potential as an effective P-gp inhibitor. Despite its promising attributes, the clinical application of P-gp inhibitors is complicated by P-gp's presence in healthy cells, such as those in the intestinal barrier and blood–brain barrier, which can lead to increased toxicity. To address these challenges, we developed a novel multifunctional nanomaterial by covalently bonding halloysite nanotubes (HNTs) with hectorite (Ht) and loading it with curcumin and doxorubicin. The efficacy of the co-delivery of curcumin and doxorubicin by HNTs-Ht nanomaterial was evaluated by cytotoxicity assays on MCF-7R cells, both in two-dimensional (2D) and in three-dimensional (3D) models. The obtained data show that curcumin causes increased doxorubicin accumulation by acting as a substrate for P-gp transport and as a stimulator of the adenosine triphosphate (ATP)-dependent drug efflux transporter on a doxorubicin-resistant breast cancer cell line. The results suggest that the HNTs-Ht nanomaterial could provide a promising approach to improve chemotherapy effectiveness by overcoming MDR and enhancing treatment outcomes.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11671670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890649","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

6-aryloxy-2-aminopyrimidine-benzonitrile hybrids as anti-infective agents: Synthesis, bioevaluation, and molecular docking 6-芳氧基-2-氨基嘧啶-苯腈杂合体抗感染药物：合成、生物评价和分子对接。

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2024-12-25 DOI: 10.1002/ardp.202400580

Abburi Naga Pranathi, Nagineni Devendra, Rakesh K. Bollikanda, Pavan K. Bangalore, Iana L. Esaulkova, Mikhail G. Mikhalsky, Maria A. Niukalova, Vladimir V. Zarubaev, Balasubramanian Sridhar, Srinivas Kantevari

{"title":"6-aryloxy-2-aminopyrimidine-benzonitrile hybrids as anti-infective agents: Synthesis, bioevaluation, and molecular docking","authors":"Abburi Naga Pranathi, Nagineni Devendra, Rakesh K. Bollikanda, Pavan K. Bangalore, Iana L. Esaulkova, Mikhail G. Mikhalsky, Maria A. Niukalova, Vladimir V. Zarubaev, Balasubramanian Sridhar, Srinivas Kantevari","doi":"10.1002/ardp.202400580","DOIUrl":"10.1002/ardp.202400580","url":null,"abstract":"This report explores the potential of novel 6-aryloxy-2-aminopyrimidine-benzonitrile scaffolds as promising anti-infective agents in the face of the increasing threat of infectious diseases. Starting from 2-amino-4,6-dichloropyrimidine, a series of 24 compounds inspired from the antiviral drugs dapivirine, etravirine, and rilpivirine were designed and synthesized via a two-step reaction sequence in good yields. Biological testing of synthetic analogs revealed potent inhibition against both viral and tuberculosis targets. Notably, compounds 5p (2,4-dimethyl substitution; IC50 = 44 ± 4.9 µM; selectivity index [SI] = 20) and 5 s (3-thiophenphenyl; IC50 = 6 ± 1 µM; SI = 120) showed significant antiviral activity against pandemic influenza virus A/Puerto Rico/8/34 (H1N1) with positive toxicity profiles and also exhibited good IC50 values (5p, IC50 = 10 ± 2 µM; SI = 9 and 5 s, IC50 = 16 ± 2 µM; SI = 60) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Wuhan strain) compared with favipiravir. In addition, analogs 5a, 5r, 5t, and 5u showed good antitubercular activity against Mycobacterium tuberculosis H37Rv strain and compounds 3, 5f, 5n, and 5q showed moderate antibacterial activity against gram+ve and gram-ve bacterial strains, suggesting that this scaffold has a broad spectrum of therapeutic effects.","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890645","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