Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/0115734064321632241022082028
Cristina Martinez-Nava, Cuauhtemoc Perez-Gonzalez, Miguel Ángel Zavala-Sanchez, Erick Cuauhtemoc Perez-Montiel, Francisco Javier Lopez-Munoz, Carlos Alberto Mendez-Cuesta
{"title":"Characterization of the Cytotoxic Effect of Naphthalenacetamides Hydrochlorides on Cervical Cancer-Derived Cells.","authors":"Cristina Martinez-Nava, Cuauhtemoc Perez-Gonzalez, Miguel Ángel Zavala-Sanchez, Erick Cuauhtemoc Perez-Montiel, Francisco Javier Lopez-Munoz, Carlos Alberto Mendez-Cuesta","doi":"10.2174/0115734064321632241022082028","DOIUrl":"10.2174/0115734064321632241022082028","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer is a global health problem due to its high incidence and prevalence in women, mainly in third-world countries. For the treatment of this disease, there are different therapeutic options, but these are not always effective, which gives rise to the search for new compounds using cheminformatics tools.</p><p><strong>Objective: </strong>The objective of this study was to design, synthesize, and biologically evaluate N-(2- morpholinoethyl)-2-(naphthalen-2-yloxy)acetamide hydrochloride (1) and 2-(naphthalen-2-yloxy)- N-(2-(piperidin-1-yl)ethyl)acetamide hydrochloride (2) on the HeLa cell line <i>in vitro</i>. The referenced cell line from the American Type Culture Collection (ATCC<sup>®</sup>CCL-2<sup>™</sup>) was used, and the effect on cell viability was determined by MTT metabolic reduction-based assay at 24, 48, and 72 h.</p><p><strong>Methods: </strong>Therapies directed at the σ1 receptor may be a treatment alternative since this receptor modulates the processes of cell proliferation and angiogenesis, producing cytoprotective or cytotoxic actions depending on the ligand with which it is coupled.</p><p><strong>Results: </strong>The analysis showed that compounds 1 and 2 presented activity on HeLa cancer cells and viability at micromolar concentrations (1.923 μmol/mL and 0.374 μmol/mL, respectively). Moreover, the effect was maintained for 72 h.</p><p><strong>Conclusion: </strong>Naphthaleneacetamide derivatives exhibited an inhibitory effect on the HeLa cell line, and the OSIRIS program predicted less toxicity than cisplatin.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 3","pages":"239-249"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605514","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}
Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/0115734064325532241002105426
Mikhail D Nekrasov, Dmitrii V Pyshnyi, Maxim S Kupryushkin
{"title":"Application of Iodine-Amine Oxidation Approach in the Synthesis of Various N-Alkyl Phosphoramidate Oligonucleotide Derivatives.","authors":"Mikhail D Nekrasov, Dmitrii V Pyshnyi, Maxim S Kupryushkin","doi":"10.2174/0115734064325532241002105426","DOIUrl":"10.2174/0115734064325532241002105426","url":null,"abstract":"<p><strong>Introduction: </strong>Nowadays, use of phosphate modifications in oligonucleotide backbone has become a common approach for imbuing its structure with the desired beneficial properties. The recent advances in successful application of different classes of phosphate modifications in the design of therapeutic oligonucleotides have led to a renewed interest in the development of approaches for introducing diverse classes of phosphate modifications.</p><p><strong>Methods: </strong>This study aims to investigate the efficiency and optimize protocols for the application of the iodine-amine oxidation reaction to produce various N-alkyl phosphoramidate oligonucleotide derivatives during the conventional solid-phase phosphoramidite synthesis method.</p><p><strong>Results: </strong>Various solvents and drying reagents were tested, and it was evaluated that even minor traces of water in a reaction mixture had a significant impact on yield. Using set of commercially available amines, it was shown that steric accessibility is a more critical parameter than nucleophilicity of the amino group in oxidative amination reaction. It was demonstrated that through use of amino alcohols and diamines during iodine-amine oxidation step various branched oligonucleotide structures can be synthesized.</p><p><strong>Conclusion: </strong>The obtained data indicates that the oxidative amination approach can be a promising tool for preparing various oligonucleotide derivatives during solid-phase synthesis without the use of specialized phosphoramidite monomers.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 3","pages":"229-238"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605507","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":"Exploring <i>Cannabis sativa L</i> for Anti-Alzheimer Potential: An Extensive Computational Study including Molecular Docking, Molecular Dynamics, and ADMET Assessments.","authors":"Hassan Nour, Imane Yamari, Oussama Abchir, Nouh Mounadi, Abdelouahid Samadi, Salah Belaidi, Samir Chtita","doi":"10.2174/0115734064318657240822064240","DOIUrl":"https://doi.org/10.2174/0115734064318657240822064240","url":null,"abstract":"<p><strong>Introduction: </strong>Cholinesterase enzymes play a pivotal role in hydrolyzing acetylcholine, a neurotransmitter crucial for memory and cognition, into its components, acetic acid, and choline. A primary approach in addressing Alzheimer's disease symptoms is by inhibiting the action of these enzymes.</p><p><strong>Methods: </strong>With this context, our study embarked on a mission to pinpoint potential Cholinesterase (ChE) inhibitors using a comprehensive computational methodology. A total of 49 phytoconstituents derived from <i>Cannabis sativa L</i> underwent <i>in silico</i> screening via molecular docking, pharmacokinetic and pharmacotoxicological analysis, to evaluate their ability to inhibit cholinesterase enzymes. Out of these, two specific compounds, namely tetrahydrocannabivarin and Δ-9- tetrahydrocannabinol, belonging to cannabinoids, stood out as prospective therapeutic agents against Alzheimer's due to their potential as cholinesterase inhibitors. These candidates showcased commendable binding affinities with the cholinesterase enzymes, highlighting their interaction with essential enzymatic residues.</p><p><strong>Results: </strong>They were predicted to exhibit greater binding affinities than Rivastigmine and Galantamine. Their ADMET assessments further classified them as viable oral pharmaceutical drugs. They are not expected to induce any mutagenic or hepatotoxic effects and cannot produce skin sensitization. In addition, these phytoconstituents are predicted to be BBB permeable and can reach the central nervous system (CNS) and exert their therapeutic effects. To delve deeper, we explored molecular dynamics (MD) simulations to examine the stability of the complex formed between the best candidate (Δ-9-tetrahydrocannabinol) and the target proteins under simulated biological conditions. The MD study affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes.</p><p><strong>Conclusion: </strong>Our research outcomes provide valuable insights, offering a clear direction for the pharmaceutical sector in the pursuit of effective anti-Alzheimer treatments.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 5","pages":"367-384"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317310","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 Step Towards Development and Bio-evaluation of a Novel Radio-ligand <sup>99m</sup>Tc-CYX-DTPA Targeting Sigma 2 Receptors.","authors":"Ritika Chaudhary, Shubhra Chaturvedi, Divya Gautam, Vishakha Chaudhary, Deepika Sharma, Presenjit, Aastha Garg, Madhu Chopra, Anil Kumar Mishra","doi":"10.2174/0115734064329861250122113332","DOIUrl":"https://doi.org/10.2174/0115734064329861250122113332","url":null,"abstract":"<p><strong>Introduction: </strong>Development of theranostics agents targeted towards particular receptors can effectively help in the management of cancer. The overexpression of the sigma-2 receptor (S2R) in tumors establishes it as a prominent biomarker for cancer cells.</p><p><strong>Methods: </strong>Radiotheranostics rely on the design of specific molecules having versatility in applications of diagnosis and therapy by merely changing the radioisotope. We have designed a novel radiotheranostic S2R-targeted ligand using cyclohexylpiperazine and performed docking studies to narrow down the potential efficacious ligand. The potential molecule with G-score = -7.0 kcal/mol, was then synthesized using a three steps reaction including conjugation of 2-(4- cyclohexylpiperazine-1-yl)ethyl(CYX) with DTPA chelator. Subsequently, the molecule has been radiolabelled with <sup>99m</sup>Tc using stannous chloride as a reducing agent, and a radiolabellieng efficiency of 95.0 ± 0.59% for <sup>99m</sup>Tc-CYX-DTPA. As proof of concept, the molecule has been evaluated for its binding affinity and specificity using sigma receptors isolated from the liver membrane homogenates of mice. The binding affinity was found to be K<sub>d</sub> = 12.84 ± 0.395 nM; B<sub>max</sub> = 0.5258 ± 0.001 fmol/mg, indicating a high affinity for the receptors.</p><p><strong>Results: </strong>In addition, the molecule was also assessed for biocompatibility using haemolysis analysis and cytotoxicity on HEK cells and MDA-MB-23, wherein the molecule showed no significant cytotoxicity up to 72 h on HEK cells and 32.42% cytotoxicity on MDA-MB-231 cells.</p><p><strong>Conclusion: </strong>The future work will concentrate on the demonstration of <i>in vivo</i> targeting and sitespecific accumulation of the molecule along with its suitability for theranostics applications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 6","pages":"582-593"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149491","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}
Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/0115734064333811240928105309
Soykan Agar
{"title":"<i>De novo</i> Drug Design and Repurposing to Suppress Liver Cancer <i>via</i> VEGF-R1 Mechanism: Comprehensive Molecular Docking, Molecular Dynamics Simulations and ADME Estimation.","authors":"Soykan Agar","doi":"10.2174/0115734064333811240928105309","DOIUrl":"https://doi.org/10.2174/0115734064333811240928105309","url":null,"abstract":"<p><strong>Aim: </strong>The aim is to halt the progression of liver cancer (Hepatocellular carcinoma) by suppressing the VEGF-R1 receptor using Myricetin and its <i>de novo</i>-designed analogues.</p><p><strong>Background: </strong>VEGF/VEGFR autocrine signalling promotes the growth, progression, and metastasis of Hepatocellular carcinoma, making the development of molecularly targeted therapies highly feasible. Invasive and metastatic behaviours in various cancers, including hepatocellular carcinoma (HCC), are closely monitored through the use of VEGF signalling pathway inhibitors. Specifically in HCC, VEGFR-1 facilitates the invasive capabilities of cancer cells primarily by triggering the epithelial-mesenchymal transition (EMT) process. VEGFR-1 significantly influences the activity of proteolytic enzymes that are critical for the invasive behaviour of HCC cells. Notably, a novel mechanism has been discovered where VEGFR-1 activation leads to the upregulation of MMP-9, thereby enhancing the invasiveness of HCC cells. The scientists, in their study, have elaborated on the various antiangiogenic agents developed for the treatment of HCC. They have highlighted clinical trials that explore the efficacy of these treatments, which include the application of monoclonal antibodies and small-molecule kinase inhibitors designed to target specific pathways involved in tumour angiogenesis and growth.</p><p><strong>Objective: </strong>Creating a pharmaceutical chemistry table regarding \"Structure-Activity Relationship of New Compounds on anticancer''. To do so, Myricetin and its <i>de novo</i> designed structured variants were used in molecular docking, molecular dynamics, cluster analyses, and 1H NMR estimation to specifically understand and enhance the mechanism of suppressing the VEGF-R1 receptor.</p><p><strong>Methods: </strong>Proper ligands (Myricetin and its analogues) and receptor (VEGF-R1) preparations, and optimizations were done using the density functional theory (DFT)/B3LYP function along with the 6-31G(d,p) basis set principle in the latest software programs such as Gaussian 09, Gauss View 6.0 and Avogadro. Then using PyRx and Autodock Vina 1.1.2., many molecular docking trials were achieved with 100 posed simulations in each run. An extensive cluster analysis was performed to identify the most optimal docking poses with the highest accumulation and most favourable binding interactions, ensuring the accuracy of the study. The docking configurations that exhibited the most precise and accurate poses with lowest inhibition constants were chosen as initial structured data for subsequent Molecular Dynamics (MD) simulations for each drug candidate. To verify the molecular docking results, MD runs were achieved in our supercomputers and the trajectory analyses were made. The data confirmed what was found in molecular docking results, verifying the high efficiency of the druggable molecules' inhibition towards VEGF-R1.</p><p><strong>Results: </stron","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 6","pages":"501-515"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149511","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}
Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/0115734064325144240823073504
Mohammad A Khanfar, Mohammad Saleh
{"title":"Design and Synthesis of 3-(Phenylsulfonamido)benzamide Derivatives as Potent Carbonic Anhydrase IX Inhibitors: Biological Evaluations and Molecular Modeling Studies.","authors":"Mohammad A Khanfar, Mohammad Saleh","doi":"10.2174/0115734064325144240823073504","DOIUrl":"10.2174/0115734064325144240823073504","url":null,"abstract":"<p><strong>Introduction: </strong>Carbonic anhydrase IX (CAIX) is known to be overexpressed in various tumors and plays a significant role in tumor development and progression.</p><p><strong>Methods: </strong>A series of 3-(benzylsulfonamido)benzamides derivatives was synthesized and tested for their CAIX inhibitory activities. The two most active compounds were subjected to cytotoxicity testing against a panel of 60 cancer cell lines.</p><p><strong>Results: </strong>Many of the synthesized compounds successfully inhibited CAIX activities, exhibiting IC<sub>50</sub> values in the low nanomolar range. The most potent CAIX inhibitor was compound 14, with an IC<sub>50</sub> of 140 nM. Structure-activity relationship analysis of the synthesized compounds supported with molecular docking revealed strong coordination of sulfonamide moiety with the catalytic Zn<sup>2+</sup> metal, hydrophobic interactions of the benzylsulfonamido ring with a hydrophobic pocket, and π- stacking interactions of the aryl ring with an aromatic surface. The two most active analogues (10 and 14) were further tested for their antiproliferative activities in the NCI-60 human tumor cell lines. Notably, compound 14 demonstrated potent growth inhibitory effects against several cancer cell lines.</p><p><strong>Conclusion: </strong>The synthesized analogues represent a novel scaffold for the treatment of different types of cancer by targeting CAIX.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 2","pages":"160-167"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502269","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}
Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/0115734064326002240912102121
Monika Chauhan, Sumitra Nain
{"title":"One-Pot Synthesis of Benzoxazoles: A Promising Approach to Aromatic Heterocyclic Compounds Preparation.","authors":"Monika Chauhan, Sumitra Nain","doi":"10.2174/0115734064326002240912102121","DOIUrl":"10.2174/0115734064326002240912102121","url":null,"abstract":"<p><p>Considering the necessity for broad synthetic operations, integrating various reactions into a single pot operation is an intriguing approach to improve synthetic efficiency. One-pot operations may serve as an effective way to minimize the amount of chemical waste generated, save time, avoid multiple purification processes, accomplish numerous transformations, and make multiple bonds in one pot. Therefore, \"pot economy\" should be considered while designing a synthesis process, since a one-pot reaction can be effective and environmentally safe. Outstanding synthesis has rapidly increased over the last ten years. This study's main goal was to illustrate various one-pot methods that lead to advantageous synthesis.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 4","pages":"251-263"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017585","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}
Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/0115734064318361240827072124
Raghav Mishra, Jayze da Cunha Xavier, Nitin Kumar, Gaurav Krishna, Prashant Kumar Dhakad, Helcio Silva Dos Santos, Paulo Nogueira Bandeira, Tigressa Helena Soares Rodrigues, Diego Romao Gondim, Walber Henrique Ferreira Ribeiro, Draulio Sales da Silva, Alexandre Magno Rodrigues Teixeira, Wandresa Francelino Pereira, Emmanuel Silva Marinho, Sucheta
{"title":"Exploring Quinoline Derivatives: Their Antimalarial Efficacy and Structural Features.","authors":"Raghav Mishra, Jayze da Cunha Xavier, Nitin Kumar, Gaurav Krishna, Prashant Kumar Dhakad, Helcio Silva Dos Santos, Paulo Nogueira Bandeira, Tigressa Helena Soares Rodrigues, Diego Romao Gondim, Walber Henrique Ferreira Ribeiro, Draulio Sales da Silva, Alexandre Magno Rodrigues Teixeira, Wandresa Francelino Pereira, Emmanuel Silva Marinho, Sucheta","doi":"10.2174/0115734064318361240827072124","DOIUrl":"10.2174/0115734064318361240827072124","url":null,"abstract":"<p><strong>Objectives: </strong>Malaria continues to be the primary cause of mortality worldwide, and timely recognition and prompt intervention are crucial in mitigating adverse consequences. This review article aims to examine the effectiveness and structural characteristics of quinoline-based compounds as antimalarial agents. It specifically focuses on their therapeutic effects as well as potential prospects for exploring structure-activity relationship (SAR). In addition, this study aims to identify lead compounds that can efficiently battle multidrug-resistant forms of <i>Plasmodium falciparum </i> and <i>Plasmodium vivax</i>.</p><p><strong>Methods: </strong>A comprehensive review was conducted to evaluate the effectiveness of quinoline-based antimalarial medications in eradicating <i>P. falciparum</i> and <i>P. vivax</i>. The mechanism of action and SAR of these compounds were analyzed.</p><p><strong>Results: </strong>Quinoline-based antimalarials demonstrated significant effectiveness in eliminating <i>P. falciparum</i> parasites, particularly in regions severely impacted by malaria, including Africa and Asia. These compounds were found to exhibit tolerance and immune-modulating properties, indicating their potential for more widespread utilization. The investigation identified various new quinoline compounds with improved antimalarial activity, including metal-chloroquine complexes, diaminealkyne chloroquines, and cinnamoylated chloroquine hybrids. This study explored different mechanisms by which these compounds interact with parasites, including their ability to accumulate in the parasite's acidic food vacuoles and disrupt heme detoxification. The derivatives demonstrated strong efficacy against chloroquine-resistant strains and yielded positive results.</p><p><strong>Conclusion: </strong>Quinoline-based compounds represent a promising avenue for combating malaria due to their demonstrated efficacy against <i>P. falciparum</i> and <i>P. vivax</i> parasites. Further research on their mechanisms of action and SAR could lead to the development of more effective antimalarial medications.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 2","pages":"96-121"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502270","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}
Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/0115734064310458240719071823
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
{"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 (IC<sub>50</sub>) 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}
Medicinal ChemistryPub Date : 2025-01-01DOI: 10.2174/157340642105250416095220
Yasuhiro Ozeki, S M Abe Kawsar
{"title":"Carbohydrates in Computational and Medicinal Chemistry.","authors":"Yasuhiro Ozeki, S M Abe Kawsar","doi":"10.2174/157340642105250416095220","DOIUrl":"https://doi.org/10.2174/157340642105250416095220","url":null,"abstract":"","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":"21 5","pages":"331-333"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317309","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}