Archiv der Pharmazie最新文献

{"title":"PDE4B Inhibition: Exploring the Landscape of Chemistry Behind Specific PDE4B Inhibitors, Drug Design, and Discovery","authors":"Veena Ks,&nbsp;Ashish Sunil Akkewar,&nbsp;Meshram Nikhil Murtikumar,&nbsp;Kalyan K. Sethi","doi":"10.1002/ardp.70030","DOIUrl":"https://doi.org/10.1002/ardp.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>Phosphodiesterase 4 (i.e., PDE4A, PDE4B, PDE4C, and PDE4D) is an enzyme group that regulates intracellular cyclic adenosine monophosphate (cAMP) levels, which are involved in multiple physiological activities. PDE4B and PDE4D have closely identical amino acid sequences (~80%) and are highly expressed due to increases in cAMP levels and other factors like hormones, neurotransmitters, <i>etc</i>. Thus, selective PDE4B suppression and discovery of its inhibitors are quite challenging. The PDE4B isoform, highly expressed in inflammatory disorders, cancers, cognitive and metabolic disorders, represents a potential target for therapy and drug discovery. PDE4B inhibition is what produces the positive therapeutic results, whereas nonselective PDE4D inhibition leads to unfavorable side effects. In the realm of modern research, selective PDE4B inhibition is important and ought to be achieved to improve the safety and effectiveness of its inhibitors. This article highlights the advances in the development of selective PDE4BIs during the past decade. The chemical architecture for selective inhibitors includes different functional groups capable of producing the essential interactions with the catalytic domain of PDE4B. The In Silico interaction analysis revealed the importance of PDE4BIs' interaction with the Q (PHE-446 and GLU-443), M (Zn²⁺ and Mg²⁺), and S pockets, along with the CR3 domain of the enzyme. Additionally, a few of the natural products and their derivatives are also being explored as PDE4BIs. Dual activities of the PDE4BIs, i.e., PDE4B inhibition along with TRPA1 and M₃ inhibition and β₂ activation, are the future perspective for the treatment of inflammatory diseases like psoriasis, chronic obstructive pulmonary disease (COPD), asthma, autoimmune disorders, etc.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615208","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":"Nature-Inspired Compounds Targeting Escherichia coli WrbA as Biofilm-Modulating Agents: Computational Design, Synthesis, and Biological Evaluation","authors":"Matteo Mori,&nbsp;Enrico Mario Alessandro Fassi,&nbsp;Federica Villa,&nbsp;Erica Ginevra Milano,&nbsp;Fabio Forlani,&nbsp;Francesca Cappitelli,&nbsp;Alessandro Ratti,&nbsp;Fiorella Meneghetti,&nbsp;Gabriella Roda,&nbsp;Giovanni Grazioso,&nbsp;Stefania Villa","doi":"10.1002/ardp.70049","DOIUrl":"https://doi.org/10.1002/ardp.70049","url":null,"abstract":"<p>Biofilms pose significant challenges in multiple settings due to their resistance to conventional treatments. In this study, we designed and synthesized a novel class of nature-inspired 5,7-dihydroxy-2,2-dimethylchroman-4-one derivatives as binders of WrbA, a potential target for biofilm modulation. Using a structure-based computational approach, a small library of analogs with varied amide moieties was developed and synthesized. The evaluation of their binding affinity to WrbA demonstrated good-to-excellent <i>K</i>_d values, as confirmed by microscale thermophoresis (MST). Antibiofilm assays against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> revealed different modulating effects on biofilm formation, conceivably linked to ROS production. These findings emphasize the importance of ROS levels in biofilm, as well as the pivotal role of WrbA as a target in its regulation.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598543","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":"2-Propyl-3-Aminoquinazoline-4(3H)-one Derivatives as Potential Androgen Receptor Inhibitors: Synthesis and Cytotoxicity Against PC3 Cell Line via In Vitro and In Silico Studies","authors":"Halil Şenol,&nbsp;Furkan Çakır,&nbsp;Şeyma Ateşoğlu,&nbsp;Pelin Tokalı,&nbsp;Ayşe Merve Şenol,&nbsp;Fahri Akbaş,&nbsp;Feyzi Sinan Tokalı","doi":"10.1002/ardp.70048","DOIUrl":"https://doi.org/10.1002/ardp.70048","url":null,"abstract":"<div>\u0000 \u0000 <p>Twenty-one novel quinazolin-4(3<i>H</i>)-one derivatives were synthesized and evaluated for their cytotoxic effects against the PC3 prostate cancer cell line. Structural characterization was performed using FTIR, NMR, and HRMS spectroscopy. Cytotoxicity assays revealed that compound <b>1</b> exhibited the highest potency (IC₅₀ = 4.29 ± 0.32 µM) and selectivity (SI = 20.1) against PC3 cells, surpassing the reference drug sorafenib. Compounds <b>10</b> and <b>11</b> also demonstrated significant selectivity (SI = 12.7 and 12.4, respectively), making them promising candidates for further investigation. Molecular docking studies confirmed strong binding affinities to the androgen receptor (AR), with compound <b>1</b> displaying the most favorable interaction (IFD Glide Score = −15.137 kcal/mol, MM-GBSA = –72.11 kcal/mol). MD simulations further supported the stability of compound <b>1</b> within the receptor binding site, highlighting key hydrogen bonding and π–π stacking interactions. ADME predictions indicated favorable pharmacokinetic properties, with all active compounds complying with drug-likeness criteria and exhibiting high oral absorption. Overall, these findings suggest that quinazolinone derivatives, particularly compound <b>1</b>, hold significant potential as selective anticancer agents targeting prostate cancer.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589609","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":"Click Chemistry-Aided Synthesis of Triazole-Tethered Benzothiazoles as Novel Multifunctional Agents Against Alzheimer's Disease","authors":"Mostafa M. Elbadawi,&nbsp;Abdullah A. Elgazar,&nbsp;Ahmed A. Hefny,&nbsp;Maha-Hamadien Abdulla,&nbsp;Thamer bin Traiki,&nbsp;Eslam Roshdy,&nbsp;Mohammad M. Al-Sanea,&nbsp;Manabu Abe,&nbsp;Wagdy M. Eldehna,&nbsp;Praveen P. N. Rao,&nbsp;Abdelrahman Hamdi","doi":"10.1002/ardp.70046","DOIUrl":"https://doi.org/10.1002/ardp.70046","url":null,"abstract":"<div>\u0000 \u0000 <p>In the current medical era, Alzheimer's disease (AD) stands as a challenging multifaceted neurodegenerative disorder characterized by diverse pathological features that necessitate the development of multi-target directed ligands (MTDLs) as a promising therapeutic approach. This study reports the design and synthesis of triazole-tethered benzothiazole derivatives (<b>10a–r</b> and <b>11a–e</b>) as MTDLs for AD. These molecules have been evaluated for their potential to inhibit cholinesterases, amyloid-β (Aβ) aggregation, and their reactive oxygen species (ROS) scavenging ability. Benzothiazoles <b>10f</b>, <b>10l</b>, and <b>11c</b> exhibited good inhibition of human acetylcholinesterase (<i>h</i>AChE) with IC₅₀ values of 100, 110, and 140 nM, respectively, and were better than tacrine (IC₅₀ = 160 nM). Furthermore, they inhibited Aβ42 aggregation with percent inhibition of 49.4%, 45.1%, and 39.3%, respectively. It should be emphasized that the most potent <i>h</i>AChE and Aβ42 dual inhibitors, <b>10f</b> and <b>10l</b>, displayed efficient antioxidant activities (57.2% and 47.5%, respectively) and were better than resveratrol (40.8%). Noteworthy, the developed molecules were not cytotoxic to mouse hippocampal neuronal cells (HT22) at 25 µM, with cell viability ranging from 79.2% to 113.3%, highlighting their potential to be considered as novel scaffolds for CNS drug development. A molecular docking study proposed that <b>10f</b> and <b>10l</b> interacted with both the catalytic and peripheral active sites of <i>h</i>AChE similar to donepezil and displayed favorable binding. Also, the docking study suggested the binding mode of <b>10f</b> to Aβ40 and Aβ42. These results show that benzothiazoles <b>10f</b> and <b>10l</b> are promising candidates for the development of novel MTDLs for the effective management of AD.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598723","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, Anti-Alzheimer Evaluation and In Silico Study of 4-Methoxyphenyl)Sulfonyl Indole Hybrid Thiosemicarbazones","authors":"Uzma Ghaffar,&nbsp;Zahra Batool,&nbsp;Mussarat Tasleem,&nbsp;Nastaran Sadeghian,&nbsp;Parham Taslimi,&nbsp;Suraj N. Mali,&nbsp;Kholood A. Dahlous,&nbsp;Rahul D. Jawarkar,&nbsp;Shailesh S. Gurav,&nbsp;Xianliang Zhao,&nbsp;Iqra Munir,&nbsp;Zahid Shafiq","doi":"10.1002/ardp.70034","DOIUrl":"https://doi.org/10.1002/ardp.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a multifaceted neurological disorder linked to behavioral, psychological, and language abnormalities as well as memory loss. A series of 1-[(4-methoxyphenyl)sulfonyl]−1<i>H</i>-indole-3-carbaldehyde-based thiosemicarbazones <b>5(a–v)</b> had been synthesized and screened for their potential against AD. The compounds were tested for their inhibitory effects against cholinesterases (AChE and BChE) and monoamine oxidase A (MAO-A). Compounds <b>5l</b>, <b>5v</b>, and <b>5r</b> showed remarkable activity on AChE, BChE, and MAO-A enzymes, having IC₅₀ values ranging between 1.57 and 4.56 nM (<i>K</i>_i = 1.43 ± 0.44 to 3.43 ± 0.21 nM), between 25.68 and 35.06 nM (<i>K</i>_i = 22.53 ± 7.70 to 34.82 ± 2.32 nM), and between 22.98 and 27.23 nM, respectively. Compound <b>5l</b> with trifluoromethyl substitution at the 3 and 5 positions was the most effective derivative of AChE and BChE, having <i>K</i>_i values of 1.43 ± 0.44 nM and 22.53 ± 7.70 nM, respectively. Compound <b>5v</b> with chloro substitution at the 2 and 6 positions of the phenyl ring was the most potent inhibitor of MAO-A, with IC₅₀ values of 22.98 nM. Structure–activity analysis exhibited that the electron-withdrawing substituents and di-substitution on the phenyl ring play a significant role in the inhibition potential of synthesized compounds. The most effective inhibitors’ binding interactions with the active sites of AChE, BChE, and MAO-A were described via molecular docking studies. In silico ADME, pharmacokinetics, and drug-likeness studies were conducted and compared with the standard drugs galantamine and clorgyline.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598724","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":"Rational Design, Green Synthesis, and Biological Evaluation of Novel Imidazole Derivatives as Potent EGFR Inhibitors via One-Pot Four-Component Reaction","authors":"Alaa Muqbil Alsirhani,&nbsp;Ibtisam Aali,&nbsp;Modather F. Hussein,&nbsp;Nadia A. A. Elkanzi,&nbsp;Ali M. Ali,&nbsp;Moustafa O. Aboelez","doi":"10.1002/ardp.70044","DOIUrl":"https://doi.org/10.1002/ardp.70044","url":null,"abstract":"<div>\u0000 \u0000 <p>This study reports a green, efficient, and high-yielding synthesis of novel imidazole derivatives <b>5a</b>–<b>i</b> via a one-pot, four-component reaction under microwave irradiation. The optimized protocol demonstrates satisfactory yields (86%–92%), short reaction times (9–14 min), easy workup, and avoidance of toxic solvents, in accordance with sustainable chemistry principles. The antiproliferative efficacy of derivatives <b>5a</b>–<b>i</b> was evaluated against H1975, A549, and A431 cells, using the MTT assay. The results indicated that derivatives <b>5b</b> and <b>5g</b> exhibited the greatest antiproliferative activity, with IC₅₀ values of 5.22 and 6.34 µM. The values obtained were markedly inferior to those of recognized EGFR inhibitors, such as osimertinib, gefitinib, and erlotinib. Compound <b>5b</b> was exhibited as the most potent inhibitor of both EGFR^WT and EGFR^T790M kinases, with IC₅₀ values of 30.1 and 12.8 nM, respectively. The findings exceeded those of osimertinib and gefitinib, which demonstrated IC₅₀ values of 54.3, 19.1, 9.1, and 356.8 nM, respectively, which may explain its notable antiproliferative effect against the H1975 cell line. Molecular docking and dynamics simulations confirmed the stable binding of derivatives <b>5b</b> and <b>5g</b> within the EGFR active sites, aligning with experimental findings. Furthermore, in silico ADME properties for the promising EGFR inhibitors <b>5b</b> and <b>5g</b>, conducted using the egg-boiled technique, demonstrated favorable lipophilicity, G.I.T. absorption, and BBB permeability. As a result, imidazoles <b>5a–i</b>, particularly <b>5b</b> and <b>5g</b>, exhibited promising antiproliferative properties, targeting EGFR^WT and EGFR^T790M kinase inhibitors.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598772","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":"Filtering of Active Components of Fuzi Lizhong Decoction on Gastric Ulcer by UHPLC/Q-Exactive MS Uniting Network Pharmacology","authors":"Haijun Wang,&nbsp;Yang Yu,&nbsp;Kaichen Yu,&nbsp;Qingzhu Yang,&nbsp;Ming Zhao,&nbsp;Yang Xin","doi":"10.1002/ardp.70036","DOIUrl":"https://doi.org/10.1002/ardp.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>To filter the active components of Fuzi Lizhong decoction (FLD) treating gastric ulcer (GU), compound information of herbs making up FLD was collected. Components in FLD extract were identified using ultrahigh performance liquid chromatography coupled with quadrupole-exactive orbitrap mass spectrometry (UHPLC/Q-Exactive MS). After that, network pharmacology and molecular docking were applied for predicting active components. Next, GES-1 cell survival rate experiments were conducted to verify the active components. At last, real-time fluorescent quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was applied to confirm active components. Results showed that a total of 58 components in FLD were qualified and 55 of them functioned on 310 GU-relevant targets, involved in 154 signaling pathways. Through molecular docking of the top 30 components with the top 30 targets and referring to the reference, 9 components and their targets were predicted to be active components. Among them, atractylenolide II, tyrosine, and atractylenolide III were verified to inhibit GES-1 cell apoptosis, confirmed to reverse the gene expression of GU-relevant targets involving <i>PPARG</i>, <i>EGFR</i>, <i>MAPK1</i>, and <i>ESR1</i> in GES-1 cells. So, atractylenolide II, tyrosine, and atractylenolide III were considered as active components of FLD treating GU. In conclusion, active components of FLD treating GU were filtered by applying UHPLC/Q-Exactive MS, uniting network pharmacology with the assistance of molecular docking and RT-qPCR. FLD might exert anti-GU effect through atractylenolide II, tyrosine, and atractylenolide III functioning as the relevant targets.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582149","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":"Structural Optimizations on the Scaffold of 7H-Pyrrolo[2,3-d]Pyrimidine to Develop Potent iNOS Inhibitors With Improved Antiarthritis Activity In Vivo","authors":"Wenchu Wang,&nbsp;Tingsheng Qin,&nbsp;Xianjing Feng,&nbsp;Mengyang Xu,&nbsp;Zhen Ling,&nbsp;Xin Xie,&nbsp;Min Zhang,&nbsp;Yanqin Huang,&nbsp;Jiayuan Luo,&nbsp;Sisi Cao,&nbsp;Xiaoyang Yue,&nbsp;Jie Zhang,&nbsp;Fengyuan Deng,&nbsp;Linhong He","doi":"10.1002/ardp.70038","DOIUrl":"https://doi.org/10.1002/ardp.70038","url":null,"abstract":"<div>\u0000 \u0000 <p>Inducible nitric oxide synthase (iNOS) is an attractive target to develop drugs for the treatment of rheumatoid arthritis (RA), whose overexpression leads to the release of abundant NO. In this study, a series of compounds were designed and synthesized bearing the scaffold of 7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidine to improve CLogP values and in vivo anti-inflammatory activity via molecular hybridization, whose derivatives in a previous study demonstrated good inhibition toward NO production but high CLogP values and weak potency in vivo. Among them, <b>N3b</b> effectively suppressed NO production in a concentration-dependent manner (IC₅₀ = 4.66 ± 0.19 μM) in LPS-induced RAW264.7 cells. Mechanically, <b>N3b</b> mildly inhibited the protein expression of iNOS (IC₅₀ = 13.60 ± 0.39 μM), without remarkable influence on the mRNA levels of iNOS or other classical pro-inflammatory cytokines including IL-1β, IL-6, and TNF-α at the high concentration of 30 µM. With favorable drug-likeness, <b>N3b</b> significantly alleviated paw edema at the dose of 30 mg/kg in the acute inflammation model and mitigated paw swelling and joint damage at a dosage of 10 mg/kg in the chronic arthritis model. Furthermore, <b>N3b</b> did not cause any obvious weight loss and pathological changes of important organs in treated mice, indicating that <b>N3b</b> is a potent candidate iNOS inhibitor for the treatment of RA.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582037","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":"Exploring the SAR of 1,2,3-Triazoles as Tumor-Associated Carbonic Anhydrases IX and XII Inhibitors for Anticancer Applications","authors":"Naveen Chauhan,&nbsp;Neelam Yadav,&nbsp;Prince Kumar,&nbsp;Suresh Kumar,&nbsp;Ranjana Aggarwal","doi":"10.1002/ardp.70041","DOIUrl":"https://doi.org/10.1002/ardp.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>The search for novel anticancer agents has brought carbonic anhydrase (CA) isoforms IX and XII into focus due to their critical role in tumor growth and survival, particularly under hypoxic conditions. These tumor-associated enzymes regulate pH and ion transport in cancer cells, making them attractive therapeutic targets. Among the compounds explored as CA inhibitors, 1,2,3-triazoles stand out for their versatile CA inhibition potential and favorable pharmacokinetic properties. 1,2,3-triazole scaffold, easily synthesized via click reactions, offers a promising framework for developing selective inhibitors against CA IX and XII. Recent research highlights the anticancer potential of 1,2,3-triazole derivatives, which selectively inhibit these isoforms, impairing tumor microenvironment regulation and thus enhancing cancer treatment efficacy. The present review explores the structure–activity relationships (SAR) of 1,2,3-triazole scaffolds as tumor-associated CA IX and XII inhibitors. We provide insights into their design and therapeutic potential by examining key structural modifications that enhance potency and selectivity. This comprehensive analysis aims to guide the future development of 1,2,3-triazole-based CA inhibitors for use as antitumor agents.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582294","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":"Structure Characterization and Antibacterial, Antifungal, and Antiquorum-Sensing Activity of New Metabolites From the Lipophilic Fractions of Platycodon grandiflorum Root","authors":"Hyukbean Kwon,&nbsp;Jimin Moon,&nbsp;Jeong-Hyeon Kim,&nbsp;Prima F. Hillman,&nbsp;Silviani Velina,&nbsp;Joo-Won Nam,&nbsp;Sang-Jip Nam,&nbsp;Inho Choi,&nbsp;Kyung Sik Song,&nbsp;Geum Jin Kim,&nbsp;Hyukjae Choi","doi":"10.1002/ardp.70043","DOIUrl":"https://doi.org/10.1002/ardp.70043","url":null,"abstract":"<div>\u0000 \u0000 <p>The root of <i>Platycodon grandiflorum</i> has long been used as a vegetable and traditional medicine. Although the antibacterial activity of the plant's lipophilic (hexanes and dichloromethane) fractions has been reported, the specific antibacterial compounds have not been identified. In this study, chemical analysis of the lipophilic fractions of <i>P. grandiflorum</i> extracts led to the discovery of five new polyacetylenes (<b>1</b>–<b>5</b>) and nine known compounds (<b>6</b>–<b>14</b>). Their structures were elucidated and confirmed based on 1D and 2D NMR data together with mass spectra. In particular, the relative and absolute configurations of <b>1</b> were elucidated by coupling constants, NOESY and <i>J</i>-based configurational analysis in combination with Mosher's method. Compounds <b>1</b> and <b>2</b> demonstrated strong antifungal activity against <i>Candida albicans</i>. Additionally, compound <b>1</b> significantly inhibited quorum sensing in <i>Chromobacterium violaceum</i>, a commonly used biosensor strain. Compounds <b>2</b> and <b>14</b> also exhibited mild inhibitory activity. Compounds <b>8</b> and <b>12</b>–<b>14</b> exhibited potent antibacterial activity against <i>Escherichia coli</i>, <i>Kocuria rhizophila</i>, and <i>Staphylococcus aureus</i>, as well as antifungal activity against <i>Candida albicans</i>. These compounds may be responsible of the antimicrobial activity of <i>P. grandiflorum</i>.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 7","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582148","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}