Archiv der Pharmazie最新文献

{"title":"MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions","authors":"Yujia Zheng,&nbsp;Xiaolu Zhang,&nbsp;Ziyu Wang,&nbsp;Ruifeng Zhang,&nbsp;Huayuan Wei,&nbsp;Xu Yan,&nbsp;Xijuan Jiang,&nbsp;Lin Yang","doi":"10.1002/ardp.202400459","DOIUrl":"10.1002/ardp.202400459","url":null,"abstract":"<p>The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key component of the innate immune system that triggers inflammation and pyroptosis and contributes to the development of several diseases. Therefore, blocking the activation of the NLRP3 inflammasome has therapeutic potential for the treatment of these diseases. MCC950, a selective small molecule inhibitor, has emerged as a promising candidate for blocking NLRP3 inflammasome activation. Ongoing research is focused on elucidating the specific targets of MCC950 as well as assessfing its metabolism and safety profile. This review discusses the diseases that have been studied in relation to MCC950, with a focus on stroke, Alzheimer's disease, liver injury, atherosclerosis, diabetes mellitus, and sepsis, using bibliometric analysis. It then summarizes the potential pharmacological targets of MCC950 and discusses its toxicity. Furthermore, it traces the progression from preclinical to clinical research for the treatment of these diseases. Overall, this review provides a solid foundation for the clinical therapeutic potential of MCC950 and offers insights for future research and therapeutic approaches.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046019","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, in vitro and in silico evaluation of gallamide and selenogallamide derivatives as inhibitors of the SARS-CoV-2 main protease","authors":"Maryelle A. G. de Carvalho,&nbsp;Gabriella B. Souza,&nbsp;Tiago Tizziani,&nbsp;Carime L. M. Pontes,&nbsp;Bibiana P. Dambrós,&nbsp;Natália F. de Sousa,&nbsp;Marcus T. Scotti,&nbsp;Mario Steindel,&nbsp;Antonio L. Braga,&nbsp;Louis P. Sandjo,&nbsp;Francisco F. de Assis","doi":"10.1002/ardp.202400253","DOIUrl":"10.1002/ardp.202400253","url":null,"abstract":"<p>The present work reports the inhibitory effect of amides derived from gallic acid (gallamides) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro), along with cytotoxicity evaluation and molecular docking studies. In addition to gallamides, other relevant compounds were also synthesized and evaluated against M^pro, making a total of 25 compounds. Eight compounds presented solubility issues during the inhibitory assay and one showed no inhibitory activity. Compounds <b>3a</b>, <b>3b</b>, and <b>3f</b> showed the highest enzymatic inhibition with IC₅₀ = 0.26 ± 0.19 µM, 0.80 ± 0.38 µM, and 2.87 ± 1.17 µM, respectively. Selenogallamide <b>6a</b> exhibited IC₅₀ values of 5.42 ± 2.89 µM and a comparison with its nonselenylated congener <b>3c</b> shows that the insertion of the chalcogen moiety improved the inhibitory capacity of the compound by approximately 10 times. Regarding the cellular toxicity in THP-1 and Vero cells, compounds <b>3e</b> and <b>3g</b>, showed moderate cytotoxicity in Vero cells, while for THP-1 both were nontoxic, with CC₅₀ &gt; 150 µM. Derivative <b>3d</b> showed moderate cytotoxicity against both cell lines, whereas <b>6d</b> was moderatly toxic to THP-1. Other compounds analyzed do not induce substantial cellular toxicity at the concentrations tested. The molecular docking results for compounds <b>3a</b>, <b>3b</b>, and <b>3f</b> show that hydrogen bonding interactions involving the hydroxyl groups (OH) of the gallate moiety are relevant, as well as the carbonyl group.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986968","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":"An in-depth analysis of COVID-19 treatment: Present situation and prospects","authors":"Md Ariful Islam,&nbsp;Kalyani Pathak,&nbsp;Riya Saikia,&nbsp;Pallab Pramanik,&nbsp;Aparoop Das,&nbsp;Prasenjit Talukdar,&nbsp;Anshul Shakya,&nbsp;Surajit Kumar Ghosh,&nbsp;Udaya Pratap Singh,&nbsp;Hans Raj Bhat","doi":"10.1002/ardp.202400307","DOIUrl":"10.1002/ardp.202400307","url":null,"abstract":"<p>Coronavirus disease 2019 (COVID-19) the most contagious infection caused by the unique type of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), produced a global pandemic that wreaked havoc on the health-care system, resulting in high morbidity and mortality. Several methods were implemented to tackle the virus, including the repurposing of existing medications and the development of vaccinations. The purpose of this article is to provide a complete summary of the current state and future possibilities for COVID-19 therapies. We describe the many treatment classes, such as antivirals, immunomodulators, and monoclonal antibodies, that have been repurposed or developed to treat COVID-19. We also looked at the clinical evidence for these treatments, including findings from observational studies and randomized-controlled clinical trials, and highlighted the problems and limitations of the available evidence. Furthermore, we reviewed existing clinical trials and prospective COVID-19 therapeutic options, such as novel medication candidates and combination therapies. Finally, we discussed the long-term consequences of COVID-19 and the importance of ongoing research into the development of viable treatments. This review will help physicians, researchers, and policymakers to understand the prevention and mitigation of COVID-19.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896215","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":"Novel tetrahydropyran-triazole hybrids with antiproliferative activity against human tumor cells","authors":"Vanesa Quintana,&nbsp;Aday González-Bakker,&nbsp;Adam N. Khan,&nbsp;Juan I. Padrón,&nbsp;Danilo Davyt,&nbsp;José M. Padrón,&nbsp;Guillermo Valdomir","doi":"10.1002/ardp.202400431","DOIUrl":"10.1002/ardp.202400431","url":null,"abstract":"<p>A series of new hybrid compounds was prepared combining tetrahydropyran rings with different aromatic systems by means of a 1,2,3-triazole, using a building block strategy. The design of these structures was guided by Lead-Likeness and Molecular Analysis (LLAMA) software, adding modifications to our most potent scaffold (the tetrahydropyran ring) to generate promising “lead-like” candidates, which were subsequently compared against reported anticancer compounds. Our synthesized compounds demonstrated significant antiproliferative activity when compared with the standards cisplatin and 5-fluorouracil, across a panel of six different tumor cell lines. Moreover, compared with our group's previous hybrid compounds, these new structures exhibit similar activity while offering simpler synthesis and greater potential for structural diversification, a fact that was previously an issue. Further investigations on the most active compounds included assessments of reproductive cell survival, inhibition of cell migration, and effects on nuclear morphology, indicating potential diverse mechanisms of action for these compounds. Pharmacokinetic properties were also calculated for the whole series of compounds using the pkCSM online software.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892435","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":"Facile one-pot synthesis of N-pyridinylaminonaphthol derivatives and their antibacterial evaluation against multidrug-resistant Staphylococcus aureus","authors":"Bulti Bakchi,&nbsp;Sarvan Maddipatla,&nbsp;Khushi Gupta,&nbsp;Anuradha Singampalli,&nbsp;Deepanshi Saxena,&nbsp;Rahul Maitra,&nbsp;Puja K. Agnivesh,&nbsp;Nitin P. Kalia,&nbsp;Srinivas Nanduri,&nbsp;Siddharth Chopra,&nbsp;Venkata M. Yaddanapudi","doi":"10.1002/ardp.202400358","DOIUrl":"10.1002/ardp.202400358","url":null,"abstract":"<p>The escalating severity of the menace posed by bacterial resistance has rendered the existing antibiotics less effective, thus necessitating the discovery of new antibacterial agents. The current study reports the exploration of substituted <i>N-</i>pyridinylaminonaphthols produced by a straightforward, one-pot multicomponent reaction process as antibacterial agents. The synthesized derivatives were assessed in vitro for their antibacterial properties against a panel of bacterial pathogens. The analogs <b>4b</b>, <b>4g</b>, <b>4h</b>, <b>4i</b>, <b>4j</b>, <b>4l</b>, <b>4r</b>, and <b>4t</b> exhibited potent inhibitory activity with minimum inhibitory concentration (MIC) values of 1–2 µg/mL. Notably, <b>4b</b>, <b>4l</b>, and <b>4t</b> displayed an excellent selectivity index. Additionally, they were active against the multidrug-resistant bacterial strains, with <b>4l</b> exhibiting the best activity against methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin resistant staphylococcus aureus with a MIC of 1 µg/mL. <b>4l</b> showed synergism with gentamycin and showed bactericidal property in a concentration-dependent manner. Furthermore, the molecule <b>4l</b> inhibited the DNA gyrase supercoiling activity. Absorption, distribution, metabolism, excretion/toxicity parameters and pharmacokinetic properties were assessed via in silico techniques, which elucidate the potential mode of action. These findings demonstrate the potential of the <i>N-</i>pyridinylaminonaphthol derivatives as antibacterial agents against multidrug-resistant <i>S. aureus.</i></p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887689","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, in vitro anticancer activity, and pharmacokinetic profiling of the new tetrahydropyrimidines: Part I","authors":"Emilija Milović,&nbsp;Jovana Trifunović Ristovski,&nbsp;Srđan Stefanović,&nbsp;Jelena Petronijević,&nbsp;Nenad Joksimović,&nbsp;Ivana Z. Matić,&nbsp;Ana Đurić,&nbsp;Bojana Ilić,&nbsp;Olivera Klisurić,&nbsp;Milica Radan,&nbsp;Katarina Nikolić,&nbsp;Nenad Janković","doi":"10.1002/ardp.202400403","DOIUrl":"10.1002/ardp.202400403","url":null,"abstract":"<p>Different vanillin-based aldehydes were used to synthesize novel tetrahydropyrimidines (THPMs) <i>via</i> conventional Biginelli reaction. The THPMs were tested against human normal cells (MRC-5) and cancer cell lines (HeLa, K562, and MDA-MB-231). With IC₅₀ values of 10.65, 10.70, and 12.76 µM, compounds <b>4g</b>, <b>4h</b>, and <b>4i</b> exerted the strongest cytotoxic effects against K562 cells. The best activity was achieved for <b>4g</b> on MDA-MB-231 cells (IC₅₀ = 9.20 ± 0.14 µM). The effects of compounds <b>4g</b>, <b>4h</b>, and <b>4i</b> on the cell-cycle phase distribution of K562 cells were analyzed. Principal component analysis was carried out for the chemometrics analysis to comprehend the relationship between the anticancer activity of the THPMs, pharmacokinetic properties, and partition coefficients, as well as the relationship between the chromatographic behavior and retention parameters. The highest retention rates are found for molecules <b>4g</b>, <b>4h</b>, and <b>4i</b>, which have the longest carbon chains, indicating that the length of the alkyl chain positively affects the molecule's anticancer activity but only if the number of carbon atoms is not higher than seven. Additionally, molecular docking analysis was performed to determine the preferred binding modes of the investigated ligands (<b>4g</b>, <b>4h</b>, and <b>4i</b>) with a DNA dodecamer and bovine serum albumin.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887690","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 (8/2024)","authors":"","doi":"10.1002/ardp.202470035","DOIUrl":"10.1002/ardp.202470035","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 8","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202470035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141944975","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":"Exploration of cytotoxicity of iodoquinazoline derivatives as inhibitors of both VEGFR-2 and EGFRT790M: Molecular docking, ADMET, design, and syntheses","authors":"Marwa Alsulaimany,&nbsp;Sanadelaslam S. A. El-Hddad,&nbsp;Zuhir S. M. Akrim,&nbsp;Ahmed K. B. Aljohani,&nbsp;Basmah Almohaywi,&nbsp;Omar M. Alatawi,&nbsp;Sara A. Almadani,&nbsp;Hussam Y. Alharbi,&nbsp;Majed S. Aljohani,&nbsp;Samar F. Miski,&nbsp;Read Alghamdi,&nbsp;Khaled El-Adl","doi":"10.1002/ardp.202400389","DOIUrl":"10.1002/ardp.202400389","url":null,"abstract":"<p>Novel inhibitors of epidermal growth factor receptor (EGFR)^T790M/vascular endothelial growth factor receptor-2 (VEGFR-2) were synthesized based on the iodoquinazoline scaffold linked to different heteroaromatic, aromatic, and/or aliphatic moieties. The novel derivatives were in vitro examined for anticancer activities against A549, HCT116, michigan cancer foundation-7 (MCF-7), and HepG2 cells. Molecular modeling was applied to discover their orientation of binding with both VEGFR-2 and EGFR active sites. Compounds <b>8d</b>, <b>8c</b>, <b>6d</b>, and <b>6c</b> indicated the highest cytotoxicity with IC₅₀ = 6.00, 6.90, 6.12 and 6.24 µM, 7.05, 7.35, 6.80, and 6.80 µM, 5.75, 7.50, 6.90, and 6.95 µM, and 6.55, 7.88, 7.44, and 7.10 µM against the A549, HepG2, HCT116, and MCF-7 cell lines, correspondingly. The cytotoxicity against normal VERO (normal african green monkey kidney cells) of the extremely active eight compounds <b>6a–d</b> and <b>8a–d</b> was evaluated. Our compounds exhibited low toxicity concerning normal VERO cells with IC₅₀ = 45.66–51.83 μM. Furthermore, inhibition assays for both the EGFR^T790M and VEGFR-2 enzymes were done for all compounds. Remarkable inhibition of EGFR^T790M activity was achieved with compounds <b>6d</b>, <b>8d</b>, <b>6c</b>, and <b>8c</b> at IC₅₀ = 0.35, 0.42, 0.48, and 0.50 µM correspondingly. Moreover, remarkable inhibition of VEGFR-2 activity was achieved with compounds <b>8d</b>, <b>8c</b>, <b>6d</b>, and <b>6c</b> at IC₅₀ = 0.92, 0.95, 1.00, and 1.20 µM correspondingly. As planned, derivatives <b>6d</b>, <b>8d</b>, <b>6c</b>, and <b>8c</b> presented exceptional inhibition of both EGFR^T790M/VEGFR-2 activities. Finally, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were made for the highly active four compounds <b>6c</b>, <b>6d</b>, <b>8c</b>, and <b>8d</b> in comparison with erlotinib and sorafenib as reference standards.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873626","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":"Unlocking the potential of edible Ulva sp. seaweeds: Metabolomic profiling, neuroprotective mechanisms, and implications for Parkinson's disease management","authors":"Dalia H. Abu-Baih,&nbsp;Fatma Mohamed Abd El-Mordy,&nbsp;Entesar Ali Saber,&nbsp;Sayed Foud El-sheikh Ali,&nbsp;Mohamed Hisham,&nbsp;Mohammad A. Alanazi,&nbsp;Faisal H. Altemani,&nbsp;Naseh A. Algehainy,&nbsp;Leane Lehmann,&nbsp;Usama Ramadan Abdelmohsen","doi":"10.1002/ardp.202400418","DOIUrl":"10.1002/ardp.202400418","url":null,"abstract":"<p>Green seaweed (<i>Ulva</i> sp.) is frequently used as a food component and nutraceutical agent because of its high polysaccharide and natural fiber content in Asian countries. This study investigates both metabolomic profiling of <i>Ulva</i> sp. and the neuroprotective efficacy of its ethanol extract and its underlying mechanisms in a rotenone-induced rat model of neurodegeneration, mimicking Parkinson's disease (PD) in humans. Metabolomic profiling of <i>Ulva</i> sp. extract was done using liquid chromatography high resolution electrospray ionization mass spectrometry and led to the identification of 22 compounds belonging to different chemical classes.Catenin Beta Additionally, this study demonstrated the neuroprotective properties against rotenone-induced PD, which was achieved through the suppression of elevated levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 together with the inhibition of reactive oxygen species (ROS) generation, apoptosis, inflammatory mediators, and the phosphoinositide 3-kinases/serine/threonine protein kinase (PI3K/AKT) pathway. Using a protein–protein interaction network, AKT1, GAPDH, TNF-α, IL-6, caspase 3, signal transducer and activator of transcription 3, Catenin Beta 1, epidermal growth factor receptor, B-cell lymphoma -2, and HSP90AA1 were identified as the top 10 most significant genes. Finally, molecular docking results showed that compounds <b>1</b>, <b>3</b>, and <b>7</b> might possess a promising anti-parkinsonism effect by binding to active sites of selected hub genes. Therefore, it is hypothesized that the <i>Ulva</i> sp. extract has the potential to be further developed as a potential therapeutic agent for the treatment of PD.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858410","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":"Tail-approach based design, synthesis, and molecular modeling of benzenesulfonamides carrying thiadiazole and urea moieties as novel carbonic anhydrase inhibitors","authors":"M. İhsan Han,&nbsp;Miyase Gözde Gündüz,&nbsp;Andrea Ammara,&nbsp;Claudiu T. Supuran,&nbsp;Şengül Dilem Doğan","doi":"10.1002/ardp.202400439","DOIUrl":"10.1002/ardp.202400439","url":null,"abstract":"<p>We synthesized herein 16 compounds (<b>SUT1</b>–<b>SUT16</b>) as potential carbonic anhydrase (CA) inhibitors utilizing the tail-approach design. Based on this strategy, we connected benzenesulfonamide, the zinc-binding scaffold, to different urea moieties with the 1,3,4-thiadiazole ring as a linker. We obtained the target compounds by the reaction of 4-(5-amino-1,3,4-thiadiazol-2-yl)benzenesulfonamide with aryl isocyanates. Upon confirmation of their structures, the compounds were screened for their ability to inhibit the tumor-related human (h) isoforms human carbonic anhydrase (hCA) IX and XII, as well as the physiologically dominant hCA I and II. Most of the molecules demonstrated <i>K</i>_i values ≤ 10 nM with different selectivity profiles. The binding modes of <b>SUT9</b>, <b>SUT10</b>, and <b>SUT5</b>, the most effective inhibitors of hCA II, IX, and XII, respectively, were predicted by molecular docking. <b>SUT16</b> (4-{5-[3-(naphthalen-1-yl)ureido]-1,3,4-thiadiazol-2-yl}benzenesulfonamide) was found to be the most selective inhibitor of the cancer-associated isoforms hCA IX and XII over the off-target isoforms, hCAI and II. The interaction dynamics and stability of <b>SUT16</b> within hCA IX and XII were investigated by molecular dynamics simulations as well as dynophore analysis. Based on computational data, increased hydrophobic contacts and hydrogen bonds in the tail part of these molecules within hCA IX and XII were found as favorable interactions leading to effective inhibitors of cancer-related isoforms.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"357 11","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202400439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854333","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}