Medicinal Chemistry最新文献

{"title":"Identification of Natural Terpenoid Compounds as Potential Inhibitors of Nucleoprotein of Influenza A Virus using in silico Approach: ADMET, Molecular Docking, and Molecular Dynamic Simulation.","authors":"Md Saddam Hossain, Md Mosahaq Ali, Prithbay Raj, Md Parvez Khondokar, S M Jahurul Haque, Yousef A Bin Jardan, Samir Ibenmoussa, Mohammed Bourhia","doi":"10.2174/0115734064311430240906112547","DOIUrl":"https://doi.org/10.2174/0115734064311430240906112547","url":null,"abstract":"<p><strong>Background: </strong>We continue to struggle with the prevention and treatment of the influenza virus. The 2009 swine flu pandemic, caused by the H1N1 strain of influenza A, resulted in numerous fatalities. The threat of influenza remains a significant concern for global health, and the development of novel drugs targeting these viruses is highly desirable.</p><p><strong>Objective: </strong>The objective of this study is to explore the inhibitory potential of terpenoid compounds against the Nucleoprotein (NP) of influenza A virus, which is a highly effective drug target due to its ability to facilitate the transcription and replication of viral RNA.</p><p><strong>Method: </strong>In silico research was performed to identify potential inhibitors of NP. Molecular docking studies were conducted to assess the binding of terpenoid compounds to the active site residues of the target protein. The most promising hits were then subjected to molecular dynamics simulations to examine the stability of the protein-ligand complexes. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies and Lipinski's rule of five were employed to evaluate the drug safety and druglikeness of the compounds.</p><p><strong>Result: </strong>Docking studies revealed that the terpenoid compounds bind strongly to the active site residues of the NP protein. Molecular dynamics simulations demonstrated the stability of the proteinligand complexes for the best-hit compounds. ADMET studies and Lipinski's filter indicated that the compounds exhibit desirable drug safety and drug-likeness profiles.</p><p><strong>Conclusion: </strong>This work may contribute significantly to drug discovery and the development of therapeutic agents against the influenza A virus. The identification of terpenoid compounds that bind strongly to the NP protein and exhibit favorable drug-like properties through in silico studies provides a promising foundation for further research and the development of potential inhibitors targeting this critical viral protein.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrative Computational Approach for the Identification of C-Abl Kinase Inhibitors from Anti-Parkinson Plant-Derived Bioactive.","authors":"Haruna Isiyaku Umar, Zainab Ashimiyu-Abdusalam, Neeraj Kumar, Najwa Ahmad Kuthi, Omoboyede Victor, Zainab Naeem Abdulsalam, Elizabeth Oluwabunmi Aribo, Ridwan Opeyemi Bello, Yousef A Bin Jardan, Hiba-Allah Nafidi, Mohammed Bourhia","doi":"10.2174/0115734064310145240822060730","DOIUrl":"https://doi.org/10.2174/0115734064310145240822060730","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential. Despite three generations of tyrosine kinase inhibitors (TKIs) being explored for PD treatment, they present significant concerns including poor blood-brain barrier penetration, off-target effects, and severe side effects. Notably, there are currently no FDA-approved c-Abl kinase inhibitors in clinical usage for PD treatment, highlighting the urgent need for potent, safe, and cost-effective alternatives.</p><p><strong>Objective: </strong>This study aims to identify potential c-Abl kinase inhibitors from plant-derived compounds with reported anti-Parkinson's potential and their derivatives using molecular docking, molecular dynamics simulations (MDS), and in silico pharmacokinetics and toxicity profiling.</p><p><strong>Methods: </strong>Seventy-eight compounds sourced from literature were docked against c-Abl kinase using Maestro 12.5. The top three hit compounds, along with nilotinib (control drug), were subjected to drug-likeness, ADMET profiling using the AI Drug Lab server and 100 ns MDS using Desmond.</p><p><strong>Results: </strong>Amburoside A, diarylheptanoid MS13, and dimethylaminomethyl-substituted-curcumin showed binding affinities close to nilotinib, with values of -12.615, -12.556, and -11.895 kcal/mol respectively, compared to nilotinib's -16.826 kcal/mol. The three plant-derived compounds exhibited excellent structural stability and favorable ADMET profiles, including optimal blood-brain barrier permeation Conclusion: The three hit compounds identified in this study show potential as c-Abl kinase inhibitors. Given the absence of FDA-approved c-Abl kinase inhibitors for PD, these findings are significant as they could contribute new therapeutic options for the treatment and management of PD. However, further in vitro and in vivo experiments are necessary to validate these findings.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoindoline-1,3-dione Derivatives as Prototypes for Anticonvulsant Drug Discovery.","authors":"Rafael Consolin Chelucci, Richard Chiquetto, Diego Eidy Chiba, Cauê Benito Scarim, Chung Man Chin, Jean Leandro Dos Santos","doi":"10.2174/0115734064336758241113180402","DOIUrl":"https://doi.org/10.2174/0115734064336758241113180402","url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy encompasses numerous syndromes characterized by spontaneous, intermittent, and abnormal electrical activity in the brain. Affecting about 1-2% of the population, it is estimated that approximately 30-40% of patients experience refractory epilepsy, which does not respond to traditional anticonvulsant drugs.</p><p><strong>Aims: </strong>Therefore, developing novel, safe, and effective antiepileptic drugs remains a medical need. In this study, we synthesized a series of isoindoline-1,3-dione derivatives and evaluated their anticonvulsant effects.</p><p><strong>Results: </strong>Compounds (2a-j) and (5) were obtained with yields ranging from 52-97%. These compounds were assessed for their protective effects on the following parameters: a) time to first seizure (seizure latency), b) seizure duration, and c) mortality rate post-seizure. The most active compound, (2a), increased seizure latency, reduced seizure duration, and lowered the mortality rate.</p><p><strong>Conclusion: </strong>These findings indicate that compound (2a) is a promising new anticonvulsant prototype, offering an alternative to current anticonvulsant drugs.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrazoline Derivatives: Exploring the Synthesis and Development of New Ligands for Anti-Cancer Therapy.","authors":"Renu Sharma, Salahuddin, Avijit Mazumder, Rajnish Kumar, Anurag Chauhan, Mohamed Jawed Ahsan, Mohammad Shahar Yar, Ramish Maqsood, Saurabh Singh","doi":"10.2174/0115734064339011241129075522","DOIUrl":"https://doi.org/10.2174/0115734064339011241129075522","url":null,"abstract":"<p><p>Pyrazoline is a 5-membered ring that has two adjacent nitrogen. It has gained advanced attention from medical and organic chemists due to very low cytotoxic activities. It is applicable and more applied in research fields and has various pharmacological activities, including cardiovascular, anti-tumor, and anti-cancer properties. In this review, the main objective is to study the pharmacological aspects of pyrazoline and its derivative analogs. The present synthetic pyrazolines are better scaffolds, which show more biological and medicinal characteristics. These compounds exhibit diverse pharmacological activities, showcasing their potential as promising candidates for cancer therapy. Pyrazolines demonstrate remarkable anti-proliferative and apoptosis-inducing effects on cancer cells, attributed to their distinctive molecular structure. This review highlights the growing significance of pyrazolines in medicinal chemistry, emphasizing their role in designing novel anticancer agents. The multifaceted properties of pyrazolines offer a compelling foundation for further research, driving innovation in the quest for effective and targeted anticancer drugs.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Developments in Azetidinone-Azole Conjugates: Emerging Antimicrobial Potentials.","authors":"Dinesh Kumar Mehta, Rajiv Chaurasiya, Rina Das","doi":"10.2174/0115734064355361241230063744","DOIUrl":"https://doi.org/10.2174/0115734064355361241230063744","url":null,"abstract":"<p><p>The emergence of multidrug-resistant microbial strains poses a significant challenge to global public health. In response, researchers have been exploring innovative antimicrobial agents with enhanced efficacy and novel mechanisms of action. One promising approach involves the synthesis of hybrid molecules combining azetidinone and azole moieties, capitalizing on the respective antimicrobial properties of both structural elements. Natural and synthetic azetidinone derivatives hold a prominent position among medicinally significant compounds due to their varied and potent antibiotic activities. Interest persists in discovering new synthetic methods and refining existing ones, as well as applying these methods to create novel, biologically active azetidinone derivatives. Additionally, azoles are highly regarded in pharmaceuticals for their broad efficacy, tolerability, and oral availability. By merging these two pharmacophores, researchers aim to create compounds with synergistic or additive antimicrobial effects, potentially overcoming existing resistance mechanisms. Various synthetic strategies, including click chemistry and multicomponent reactions, have been employed to prepare these hybrid molecules efficiently. The antimicrobial potential of azetidinone-azole conjugates has been extensively evaluated against a spectrum of pathogens, including bacteria, fungi, and protozoa. These studies have demonstrated promising results, with several compounds exhibiting potent activity against both Gram-positive and Gramnegative bacteria, as well as clinically relevant fungal strains. Furthermore, SAR studies have provided valuable insights into the key structural features governing the antimicrobial properties of these conjugates, facilitating further optimization and rational design. In conclusion, the development of azetidinone-azole hybrids represents a promising avenue in the quest for novel antimicrobial agents. This study presents a comprehensive overview of recent advancements in synthesis and antimicrobial evaluation of azetidinone-azole conjugates.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine-Derived Compound Targeting mTOR and FGFR-2: A Promising Strategy for Breast, Lung, and Colorectal Cancer Therapy.","authors":"Vijay Murali Ravi Mythili, Kumaran K, Sayantani Chattopadhyay, Shahjahan Ahmad Basha, Sruthi Sekar, Sowmya Senthil, Prabhu D, Kirubakaran Rangasamy, K N ArulJothi","doi":"10.2174/0115734064346419241104110015","DOIUrl":"https://doi.org/10.2174/0115734064346419241104110015","url":null,"abstract":"<p><strong>Introduction: </strong>The marine habitat is a plentiful source of diverse, active compounds that are extensively utilised for their medicinal properties. Pharmaceutical trends have currently changed towards utilising a diverse range of goods derived from the marine environment.</p><p><strong>Method: </strong>This study aimed to examine the inhibitory effects of bioactive chemicals derived from marine algae and bacteria. The identification of these compounds was carried out through the process of Gas Chromatography-Mass Spectrometry (GC-MS) profiling. Subsequently, these compounds were subjected to docking simulations against a specific set of target proteins that are known to be frequently overexpressed in three distinct types of cancer.</p><p><strong>Result: </strong>From the docking results, the ligand 1,4:3,6:5,7-Tribenzal-beta-mannoheptitol was found to be effective against the proteins mTOR (PDB ID: 4JSV) and FGFR2 (PDB ID:6V6Q). The findings of this study highlight the significant benefits offered by the tool under investigation, which effectively enhances the efficiency of the docking procedures.</p><p><strong>Conclusion: </strong>These compounds hold significant potential for further development and exploration in the field of cancer therapeutics.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extraction, Isolation and Purification of Catechins and their Applications.","authors":"Hong-Mei Cao, Jiao-Jiao Fang, Yi-Tao Zhao, Pei-Hong Zhao, Xin Chen","doi":"10.2174/0115734064353669241212064640","DOIUrl":"https://doi.org/10.2174/0115734064353669241212064640","url":null,"abstract":"<p><p>Catechins, the main active components of tea polyphenols, boast remarkable antioxidant activities because of their unique structures. This translates to a range of potential health benefits, including fighting antibacterial, inflammation, and even cancers. However, extracting these beneficial compounds can be tricky as they're prone to degradation. Thankfully, recent advancements have yielded successful methods for isolating and purifying catechins, allowing us to obtain them in their purest form. The power of catechins isn't just theoretical. In vitro and in vivo studies have demonstrated promising results in treating various conditions like inflammation, cancer, neurodegenerative diseases, cardiovascular diseases, diabetes, and more. This review dives deep into the methods used to extract, isolate, and purify catechins. Additionally, it explores their potent antioxidant activities and exciting possibilities for future applications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Antimicrobial Activity, DFT, Molecular Docking, and Dynamic Simulations of Trityl Mannopyranoside Derivatives for Potential Antibacterial Agents.","authors":"Sabina Akter, Sarkar M A Kawsar, Gassoumi Bouzid, Mabrouk Horchani, Md Z H Bulbul, Houcine Ghalla, Hichem Ben Jannet, Supriyo Saha, Yuki Fujii, Kabir M Uddin, Ajmal R Bhat, Sumeer Ahmed, Yasuhiro Ozeki","doi":"10.2174/0115734064339243241027024304","DOIUrl":"https://doi.org/10.2174/0115734064339243241027024304","url":null,"abstract":"<p><strong>Aim: </strong>There is an urgent need for new antimicrobial compounds with alternative modes of action for the treatment of drug-resistant bacterial and fungal pathogens.</p><p><strong>Background: </strong>Carbohydrates and their derivatives are essential for biochemical and medicinal research because of their efficacy in the synthesis of biologically active drugs.</p><p><strong>Objective: </strong>In the present study, a series of methyl α-D-mannopyranoside (MMP) derivatives (2-6) were prepared via direct acylation, and their biological properties were characterized.</p><p><strong>Methods: </strong>The structures of synthesized compounds were established by analyzing their physicochemical, elemental, and spectroscopic data and evaluating their in vitro antimicrobial activities through in silico studies.</p><p><strong>Results: </strong>In the antibacterial study, compound 3 was found to be mostly active toward most of the organisms, exhibiting maximum inhibition of S. abony and minimum inhibition of P. aeruginosa. However, the MIC and MBC values revealed that this compound is highly effective against Bacillus subtilis (MIC of 0.5 μg/L and MBC of 256 μg/L). In terms of antifungal activity, 3 and 6 showed the most promising activity toward Aspergillus flavus, with an inhibition of 95.90 ± 1.0% for compound 3 and 96.72 ± 1.1% for compound 6. Moreover, density functional theory (DFT) in conjunction with the BLYP/6-311G (d) basis sets was used to calculate the dipole moment and total energy for each compound, and the molecular electrostatic potential and Mulliken charge were considered to study the electrophilicity and nucleophilicity of the groups in each compound. For dipole moment calculations, the dipole moments are in the following order: 6 < 3 < 1 < 5 < 2 < 4, inferring that compounds 2 and 4 possess a high dipole moment in comparison with the other inhibitor systems. Furthermore, molecular docking was performed against threonine synthase from B. subtilis ATCC 6633 (PDB: 6CGQ) to identify the active site of the compounds, with compound 3 showing a maximum binding energy of -10.3 kcal/mol and compound 4 exhibiting a binding energy of -10.2 kcal/mol. In addition, a 100 ns MD simulation was performed, and the results revealed a stable conformation and binding pattern within the stimulating environment.</p><p><strong>Conclusion: </strong>Our synthetic, antimicrobial, and in silico experiments revealed that MMP derivatives exhibit potential activity, providing a therapeutic target for bacteria and fungi.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WITHDRAWN: Bismuth(III) Complexes with Schiff Bases: Synthesis, Characterization, Interaction with Biomolecules, Antioxidant and Antimicrobial Activity","authors":"Maxim Y Gvozdev, Natalia V Loginova, Galina A Ksendzova, Nikolai P Osipovich, Tat'yana V Koval'chuk-Rabchinskaya, Yaroslav V Faletrov, Alina M Khodosovskaya, Anatoly N Evtushenkov","doi":"10.2174/1573406419666221118104019","DOIUrl":"10.2174/1573406419666221118104019","url":null,"abstract":"<p><p>Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40700779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Computational Approach Using α-Carbonic Anhydrase to Find Anti-<i>Trypanosoma cruzi</i> Agents.","authors":"Eyra Ortiz-Perez, Domingo Mendez-Alvarez, Alfredo Juarez-Saldivar, Adriana Moreno-Rodríguez, Mariana de Alba Alvarado, Alonzo Gonzalez-Gonzalez, Karina Vazquez, Ana Veronica Martinez-Vazquez, Benjamin Nogueda-Torres, Edgar E Lara-Ramírez, Alma D Paz-Gonzalez, Gildardo Rivera","doi":"10.2174/0115734064310458240719071823","DOIUrl":"10.2174/0115734064310458240719071823","url":null,"abstract":"<p><strong>Background: </strong>Chagas disease has an ineffective drug treatment despite efforts made over the last four decades. The carbonic anhydrase of <i>Trypanosoma cruzi</i> (α-<i>Tc</i>CA) has emerged as an interesting target for the design of new antiparasitic compounds due to its crucial role in parasite processes.</p><p><strong>Objective: </strong>The aim in this study was identify potential α-<i>Tc</i>CA inhibitors with trypanocidal activity.</p><p><strong>Methods: </strong>A maximum common substructure (MCS) and molecular docking were used to carried out a ligand- and structure-based virtual screening of ZINC20 and MolPort databases. The compounds selected were evaluated in an <i>in vitro</i> model against the NINOA strain of <i>Trypanosoma cruzi</i>, and cytotoxicity was determined in a murine model of macrophage cells J774.2.</p><p><strong>Results: </strong>Five sulfonamide derivatives (C7, C9, C14, C19, and C21) had the highest docking scores (-6.94 to -8.31 kcal/mol). They showed key residue interactions on the active site of the α-<i>Tc</i>CA and good biopharmaceutical and pharmacokinetic properties. C7, C9, and C21 had half-maximal inhibitory concentration (IC₅₀) values of 26, 61.6, and 49 μM, respectively, against NINOA strain epimastigotes of <i>Trypanosoma cruzi</i>.</p><p><strong>Conclusion: </strong>Compounds C7, C9, and C21 showed trypanocidal activity; therefore, these results encourage the development of new trypanocidal agents based in their scaffold.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":"46-60"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}