RSC medicinal chemistry最新文献

{"title":"Development of PROTACs targeting estrogen receptor: an emerging technique for combating endocrine resistance.","authors":"Rouming Peng, Xin Liu, Chun-Chi Chen, Rey-Ting Guo, Jian Min","doi":"10.1039/d4md00961d","DOIUrl":"https://doi.org/10.1039/d4md00961d","url":null,"abstract":"<p><p>Despite the success of endocrine therapies in treating ER-positive breast cancer, the development of resistance remains a significant challenge. Estrogen receptor targeting proteolysis-targeting chimeras (ER PROTACs) offer a unique approach by harnessing the ubiquitin-proteasome system to degrade ER, potentially bypassing resistance mechanisms. In this review, we present the drug design, efficacy and early clinical trials of these ER PROTACs. This review underscores the academic and industrial opportunities presented by this emerging technology, as well as the challenges that must be addressed to translate these findings into effective clinical therapies.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and biological evaluation of nitrofuranyl-pyrazolopyrimidine hybrid conjugates as potent antimicrobial agents targeting <i>Staphylococcus aureus</i> and methicillin-resistant <i>S. aureus</i>.","authors":"Sapna Saini, G Lakshma Reddy, Anjali Gangwar, Harpreet Kour, Gajanan G Nadre, Ramajayan Pandian, Sunny Pal, Utpal Nandi, Rashmi Sharma, Sanghapal D Sawant","doi":"10.1039/d4md00826j","DOIUrl":"https://doi.org/10.1039/d4md00826j","url":null,"abstract":"<p><p>Nitrofuran and pyrazolopyrimidine-based compounds possess a broad antimicrobial spectrum including Gram-positive and Gram-negative bacteria. In the present work, a series of conjugates of these scaffolds was synthesized and evaluated for antimicrobial activity against <i>Staphylococcus aureus</i> and methicillin-resistant <i>S. aureus</i> (MRSA). Many compounds showed MIC values of ≤2 μg ml^-1, with compound 35 demonstrating excellent activity (MICs: 0.7 and 0.15 μg ml^-1 against <i>S. aureus</i> and MRSA, respectively) and safety up to 50 μg ml^-1 in HepG2 cells. Compound 35 also exhibited no hemolytic activity, biofilm eradication, and effectiveness against efflux-pump-overexpressing strains (NorA, TetK, MsrA) without resistance development. It showed synergistic effects with vancomycin (<i>S. aureus</i>) and rifampicin (MRSA). Mechanistic studies revealed that compound 35 exhibits good membrane-targeting abilities, as evidenced by DAPI/PI staining and scanning electron microscopy (SEM). In an intracellular model, it reduced bacterial load efficiently in both <i>S. aureus</i> and MRSA strains. With a strong <i>in vitro</i> profile, compound 35 demonstrated favorable oral pharmacokinetics at 30 mg kg^-1 and potent <i>in vivo</i> anti-MRSA activity, highlighting its potential against antibiotic-resistant infections.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the reaction toolbox for nanoscale direct-to-biology PROTAC synthesis and biological evaluation.","authors":"Rebecca Stevens, Harry J Shrives, Jenni Cryan, Diana Klimaszewska, Peter Stacey, Glenn A Burley, John D Harling, David J Battersby, Afjal H Miah","doi":"10.1039/d4md00760c","DOIUrl":"10.1039/d4md00760c","url":null,"abstract":"<p><p>High-throughput chemistry (HTC) and direct-to-biology (D2B) platforms allow for plate-based compound synthesis and biological evaluation of crude mixtures in cellular assays. The rise of these workflows has rapidly accelerated drug-discovery programs in the field of targeted protein degradation (TPD) in recent years by removing a key bottleneck of compound purification. However, the number of chemical transformations amenable to this methodology remain minimal, leading to limitations in the exploration of chemical space using existing library-based approaches. In this work, we expanded the toolbox by synthesising a library of degraders in D2B format. First, reaction conditions are established for performing key medicinal chemistry transformations, including reductive amination, S_NAr, palladium-mediated cross-coupling and alkylation, in D2B format. Second, the utility of these alternative reactions is demonstrated by rapidly identifying developable PROTACs for a range of protein targets.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting host integrated stress response: lead discovery of flavonoid compounds active against coronaviruses PEDV and PDCoV.","authors":"Liang Yi, Yishuai Wang, Jiehuang Wang, Yihan Chen, Weixue Huang, Ying Liao, Qingwen Zhang","doi":"10.1039/d4md00846d","DOIUrl":"10.1039/d4md00846d","url":null,"abstract":"<p><p>Viral infections trigger the integrated stress response (ISR) in eukaryotic cells that leads to the activation of eIF2α kinases, the elevation of eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, and thereby the shutdown of global protein synthesis that viruses rely on to replicate. Coronaviruses and other viruses have evolved various subversion mechanisms to counteract the antiviral ISR. These intricate host-virus interactions may be exploited by pharmacologically activating the host ISR for the development of host-directed antivirals (HDAs), an increasingly relevant area of research. In this study, we have discovered a new class of flavonoid-based ISR activators that exhibit potent antiviral activity against porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV). PEDV and PDCoV are animal coronaviruses of great veterinary and economic importance, for which there are currently no effective therapeutics. The mechanistic study indicated that lead compounds 1-B and 1-C inhibit PEDV and PDCoV replication <i>via</i> upregulating eIF2α phosphorylation and thereby downregulating global protein synthesis in host cells, suggesting they are HDA antivirals.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of cyclic lipidated peptides derived from the C-terminus of Cx43 for hemichannel inhibition and cardiac endothelium targeting.","authors":"Debora Iaculli, Jade Montgomery, Arthur Lamouroux, Anne Caufriez, Rafael Gozalbes, Mathieu Vinken, Filippo Molica, Brenda R Kwak, Steven Ballet","doi":"10.1039/d4md00850b","DOIUrl":"https://doi.org/10.1039/d4md00850b","url":null,"abstract":"<p><p>A peptide segment that is 10 residues long at the C-terminal (CT) region of Cx43 is known to be involved in interactions, both with the Cx43 protein itself and with other proteins, that result in hemichannel (HC) activity regulation. Previously reported mimetic peptides based on this region (<i>e.g.</i>, <b>αCT1</b>, <b>CT10</b>) have been revealed to be promising therapeutic agents in the context of cardiovascular diseases. In this work, novel approaches, such as C- and N-terminal modification and cyclization, to improve the proteolytic stability and bioavailability of the <b>CT10</b> peptide are presented. These efforts resulted in a set of unprecedented potent cyclic inhibitors of HC-mediated ATP release with a half-life largely exceeding 24 hours. Additionally, the introduction of a lipophilic moiety with different solubilizing linkers led to the generation of a novel series of water-soluble and lipidated peptides that exhibited high inhibitory capacity in <i>in vitro</i> assays at submicromolar concentrations. A cardiac endothelium targeting strategy was also adopted, exploiting the ability of the CRPPR peptide to selectively deliver the peptides to endothelial cells.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual EGFR and telomerase inhibitory potential of new triazole tethered Schiff bases endowed with apoptosis: design, synthesis, and biological assessments.","authors":"Mohamed A Zeidan, Heba F Ashour, Asmaa S A Yassen, Ayman Abo Elmaaty, Ayman B Farag, Marwa Sharaky, Abdullah Yahya Abdullah Alzahrani, Mohammed H Al Mughram, Ahmed A Al-Karmalawy","doi":"10.1039/d4md00750f","DOIUrl":"10.1039/d4md00750f","url":null,"abstract":"<p><p>Many cancers have displayed resistance to chemotherapeutic drugs over the past few decades. EGFR has emerged as a leading target for cancer therapy <i>via</i> inhibiting tumor angiogenesis. Besides, studies strongly suggest that blocking telomerase activity could be an effective way to control the growth of certain cancer cells. Based on the fact that multi-target design rationale can afford candidates with greater treatment effectiveness. Besides, it was evidenced that inhibition of human telomerase enhances the effect of some tyrosine kinase inhibitors. So, in the current work, we aimed to design and synthesize novel 1,2,3-triazole-tethered Schiff bases (5a-l) to act as dual EGFR and telomerase inhibitors. Growth inhibition (GI)% was conducted for the synthesized compounds using a panel of eleven cancer cell lines as well as two normal cell lines. Interestingly, compound 5e displayed the highest mean GI% (76.78%) among the investigated compounds surpassing the mean GI% of the reference drug doxorubicin (65.79%). In addition, compound 5g displayed notably the lowest IC₅₀ values (13.31, 13.31, 12.62, and 31.19 μM) for the four utilized cancer cell lines HNO97, HCT116, A375, and HEPG2, respectively. Interestingly, the investigated compounds exhibited significant inhibitory potential to EGFR and telomerase protein expression; in particular, compound 5g recorded inhibitory potentials of 3.45 and 1.31 ng mL^-1, respectively. Hence, protein expression of the apoptosis-related proteins was carried out for compound 5g. Pro-apoptotic proteins (caspases 3, 8, and 9) were upregulated by 1.35, 1.55, and 1.51-fold change, respectively. Meanwhile, the anti-apoptotic proteins (CDK-2, CDK-4, and CDK-6) were downregulated by 2.91, 2.01, and 9.15-fold change, respectively, ensuring the apoptotic potential of compound 5g. Accordingly, compound 5g was selected for further investigation of its effects on cell cycle progression in A375 cancer cells. Obviously, compound 5g prompted cell cycle arrest at the G0-G1 phase. Additionally, the investigated compounds showed eligible pharmacokinetic profiles with feasible oral bioavailability. Consequently, the synthesized compounds can be treated as lead multi-target anticancer ligands for future optimization.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11708207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-(4-Bromobenzyl) tethered 4-amino aryl/alkyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-<i>d</i>]pyrimidines: design, synthesis, anticancer assessment <i>via</i> dual topoisomerase-I/II inhibition, and <i>in silico</i> studies.","authors":"Sahil Arora, Bhagyshree Patra, Isha Dhamija, Santosh Kumar Guru, Raj Kumar","doi":"10.1039/d4md00817k","DOIUrl":"10.1039/d4md00817k","url":null,"abstract":"<p><p>A series of 2-(4-bromobenzyl) tethered 4-amino aryl/alkyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-<i>d</i>]pyrimidines (7a-7u) were designed, synthesized, characterized and screened against a panel of cancer cell lines. Compound 7a, in particular, emerged as a potent antiproliferative agent against FaDu cells (HTB-43) with an IC₅₀ value of 1.73 μM. 7a induced morphological alterations in FaDu cells were observed <i>via</i> brightfield microscopy and DAPI staining, confirming cytotoxicity. Autophagy and apoptotic effects of 7a were confirmed by acridine orange staining, Rhodamine 123 staining, and western blot analysis, which revealed dose-dependent increases in LC3A/B and cleaved caspase-3 levels, respectively. Further, 7a impaired cell migration and colony formation, as demonstrated by scratch and clonogenic assays. Additionally, 7a reduced oxidative stress and induced G2/M phase cell cycle arrest in MCF-7 cells. 7a emerged as a dual topoisomerase I and II inhibitor, and results were supported by molecular docking and simulation studies. In anti-inflammatory studies, 7a exhibited selective inhibition of COX-2 over COX-1, supporting its dual anticancer and anti-inflammatory properties.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinctive roles of aquaporins and novel therapeutic opportunities against cancer.","authors":"Dharmendra Kumar Yadav, Desh Deepak Singh, Dongyun Shin","doi":"10.1039/d4md00786g","DOIUrl":"10.1039/d4md00786g","url":null,"abstract":"<p><p>Aquaporins (AQPs) are integral membrane proteins responsible for facilitating the transmembrane transport of water and small solutes. Their involvement in diverse physiological functions extends to pathological conditions, including cancer, positioning them as promising targets for anticancer therapy. Tumor cells, particularly those with high metastatic potential, exhibit elevated AQP expression, reinforcing their critical role in tumor biology. Emerging evidence highlights AQPs' involvement in key oncogenic processes such as cell migration, proliferation, and tumor-associated edema, suggesting their potential as novel therapeutic targets. Despite this, the development of selective and potent AQP inhibitors has proven challenging. Efforts to produce small-molecule AQP inhibitors have largely been unsuccessful. However, recent advancements include monoclonal human IgG antibodies targeting extracellular domains of aquaporin-4, offering new therapeutic strategies, particularly in glioblastoma, where AQP-4 is overexpressed. However, recent advancements include monoclonal human IgG antibodies targeting extracellular domains of aquaporin-4, offering new therapeutic strategies, particularly in glioblastoma, where AQP-4 is over expressed. These antibodies hold promise for selectively targeting and eradicating AQP-4-expressing cells in malignant brain tumors. This review discusses the critical role AQPs play in cancer, including their contributions to tumor cell proliferation, migration, angiogenesis, and edema formation. Additionally, we explore innovative therapeutic approaches, such as antibody-based interventions, and outline potential future research directions in AQP-targeted cancer therapies.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of coumarin-inspired bifunctional hybrids as a new class of anti-Alzheimer's agents with potent <i>in vivo</i> efficacy.","authors":"Atamjit Singh, Aman Sharma, Karanvir Singh, Kirandeep Kaur, Pallvi Mohana, Jignesh Prajapati, Uttam Kaur, Dweipayan Goswami, Saroj Arora, Renu Chadha, Preet Mohinder Singh Bedi","doi":"10.1039/d4md00782d","DOIUrl":"10.1039/d4md00782d","url":null,"abstract":"<p><p>Considering the multifactorial and complex nature of Alzheimer's disease and the requirement of an optimum multifunctional anti-Alzheimer's agent, a series of triazole tethered coumarin-eugenol hybrid molecules was designed as potential multifunctional anti-Alzheimer's agents using donepezil and a template. The designed hybrid molecules were synthesized <i>via</i> a click chemistry approach and preliminarily screened for cholinesterase and Aβ_1-42 aggregation inhibition. Among them, AS15 emerged as a selective inhibitor of AChE (IC₅₀ = 0.047 μM) over butyrylcholinesterase (BuChE: IC₅₀ ≥ 10 μM) with desired Aβ_1-42 aggregation inhibition (72.21% at 50 μM) properties. In addition, AS15 showed protective effects against DNA damage caused by hydroxyl radicals originating from H₂O₂. Molecular docking and simulation studies confirmed the favorable interactions of AChE and the Aβ_1-42 monomer desired for their inhibition. AS15 exhibited an LD₅₀ value of 300 mg kg^-1 and showed significant improvements in memory and learning behavior in scopolamine-induced cognition impairment mouse-based animal models (Y-maze test and Morris water maze test) for behavioral analysis. Overall outcomes suggest AS15 as a potential preclinical multifunctional candidate for the management of Alzheimer's disease, and it serves as a promising lead for further development of potent and safer multifunctional anti-Alzheimer's agents.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulphonyl thiourea compounds containing pyrimidine as dual inhibitors of I, II, IX, and XII carbonic anhydrases and cancer cell lines: synthesis, characterization and <i>in silico</i> studies.","authors":"Nguyen Dinh Thanh, Vu Ngoc Toan, Vu Minh Trang","doi":"10.1039/d4md00816b","DOIUrl":"https://doi.org/10.1039/d4md00816b","url":null,"abstract":"<p><p>Some novel sulphonyl thiourea derivatives (7a-m) containing 4,6-diarylpyrimidine rings were designed and synthesized using a one-pot procedure. These compounds exhibited remarkable dual inhibitory activity against human carbonic anhydrase <i>h</i>CA I, <i>h</i>CA II, <i>h</i>CA IX, and XII isoenzymes and some cancer cell lines. Among them, some thioureas had significantly more potent inhibitory activities in the order of 7l > 7c > 7f (against the <i>h</i>CA I isoform), 7f > 7b > 7c (against the <i>h</i>CA II isoform), 7c > 7g > 7a > 7b (against the <i>h</i>CA IX isoform), and 7d > 7c > 7g > 7f (against the <i>h</i>CA XII isoform). The obtained inhibitory activity data against the <i>h</i>CA IX and XII isoforms showed that compound 7c was the most potent inhibitor in this sulphonyl thiourea series against enzyme <i>h</i>CA IX, with <i>K</i> _I = 125.1 ± 12.4 nM, while compound 7d was the most potent inhibitor against enzyme <i>h</i>CA XII, with <i>K</i> _I = 111.0 ± 12.3 nM. Compound 7c exhibited strong inhibitory activity among all four tested <i>h</i>CA enzymes, while thiourea 7f was a potent inhibitor for enzymes <i>h</i>CA I, II and XII. All these compounds demonstrated non-competitive inhibition of both enzymes. Some selected potential inhibitory compounds, including 7c, 7d, and 7g, exhibited remarkable cytotoxic activity against human cancer cell lines, including human breast adenocarcinoma (MCF-7), human liver adenocarcinoma (HepG2), human cervical epithelial carcinoma (HeLa), and human lung adenocarcinoma cells (A549). These compounds exhibited low cytotoxicity in the WI-38 cell line. The compounds 7c and 7d were the most potent inhibitors against tumour-associated <i>h</i>CA IX and <i>h</i>CA XII isoenzymes. Furthermore, these compounds exhibited remarkable inhibition against some cancer cell lines, such as MCF-7, HepG2, HeLa, and A549. They were subjected to <i>in silico</i> screening for molecular docking and molecular dynamics simulations. The results of <i>in vitro</i> and <i>in silico</i> studies revealed that compounds 7c and 7d were the most promising derivatives in this series owing to their significant effects on the studied <i>h</i>CA IX and <i>h</i>CA XII isoenzymes, respectively. The results showed that the sulphonyl thiourea moiety was deeply accommodated in the active site and interacted with zinc ions in the receptors.</p>","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}