{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:51Z","timestamp":1760060691221,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The current study outlines a synthetic method for creating a new class of indazol-pyrimidine derivatives 4a\u2013h and 5a\u2013h. The new derivatives were evaluated as in vitro cytotoxic agents against three types of cancer cell lines (MCF-7, A549 and Caco-2), utilizing the MTT assay. Compounds 4a, 4c, 4d, 5a and 5f demonstrated potent cytotoxic activity against MCF-7 cell line, showing higher activity than the reference drug Staurosporine. Among the examined compounds, 5f showed a strong cytotoxic effect against all three tested cancer cells (MCF-7, A549 and Caco-2), with IC50 values of 1.858, 3.628 and 1.056 \u00b5M, respectively. In comparison, the reference drug exhibited IC50 values of 8.029, 7.354 and 4.202 \u00b5M respectively, indicating promising anti-proliferative potential of compound 5f. On the other hand, Compound 4b demonstrated the greatest potency against Caco-2 cell line, with an IC50 of 0.827 \u00b5M, markedly outperforming reference compound\u2019s IC50 of 4.202 \u00b5M. Furthermore, compound 5h revealed significant anti-proliferative activity against A549 cell line, with an IC50 value of 1.378 \u00b5M, compared to the reference drug, with an IC50 value of 7.354 \u00b5M. Additionally, the molecular docking study revealed a strong binding affinity of compound 5f within the binding site of the c-Kit tyrosine kinase protein, and the molecular dynamics study confirmed its stability.<\/jats:p>","DOI":"10.3390\/molecules30183773","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T11:00:00Z","timestamp":1758106800000},"page":"3773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Indazol-Pyrimidine Hybrids: Design, Synthesis, and Antiproliferative Activity Against Human Cancer Cell Lines"],"prefix":"10.3390","volume":"30","author":[{"given":"Hanaa M.","family":"Al-Tuwaijri","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed A.","family":"El-Rashedy","sequence":"additional","affiliation":[{"name":"Department of Natural and Microbial Products National Research Center, El Buhouth Street, Dokki, Cairo 12622, Egypt"},{"name":"Department Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-2282","authenticated-orcid":false,"given":"Siddique Akber","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0181-6330","authenticated-orcid":false,"given":"Aliyah","family":"Almomen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamad M.","family":"Alkahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebtehal S.","family":"Al-Abdullah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mogedda E.","family":"Haiba","sequence":"additional","affiliation":[{"name":"Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Division, National Research Center, El Buhouth Street, Dokki, Cairo 12622, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jcrpr.2017.07.001","article-title":"Review of Cancer from Perspective of Molecular","volume":"4","author":"Hassanpour","year":"2017","journal-title":"J. Cancer Res. Pract."},{"key":"ref_2","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1080\/14796694.2024.2387526","article-title":"Identifying and Addressing the Needs of Caregivers of Patients with Cancer: Evidence on Interventions and the Role of Patient Advocacy Groups","volume":"20","author":"Dave","year":"2024","journal-title":"Futur. Oncol."},{"key":"ref_4","unstructured":"(2025, January 30). Global Cancer Burden Growing, Amidst Mounting Need for Services. Available online: https:\/\/www.who.int\/news\/item\/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tyli\u0144ska, B., Wiatrak, B., Czy\u017cnikowska, \u017b., Cie\u015bla-Niechwiadowicz, A., G\u0119barowska, E., and Janicka-K\u0142os, A. (2021). Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083825"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1021\/jo0524831","article-title":"N,N-Bond-Forming Heterocyclization: Synthesis of 3-Alkoxy-2H-Indazoles","volume":"71","author":"Mills","year":"2006","journal-title":"J. Org. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1021\/jm950556a","article-title":"Structure\u2212Activity Relationships among 2-Substituted 5,6-Dichloro-, 4,6-Dichloro-, and 4,5-Dichloro-1-[(2-Hydroxyethoxy)Methyl]- and -1-[(1,3-Dihydroxy-2-Propoxy)Methyl]Benzimidazoles","volume":"39","author":"Saluja","year":"1996","journal-title":"J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"132734","DOI":"10.1016\/j.molstruc.2022.132734","article-title":"An in Vitro and in Silico Study on the Synthesis and Characterization of Novel Bis(Sulfonate) Derivatives as Tyrosinase and Pancreatic Lipase Inhibitors","volume":"1259","author":"Korkmaz","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lolak, N., Akocak, S., T\u00fcrke\u015f, C., Taslimi, P., I\u015f\u0131k, M., Beydemir, \u015e., G\u00fcl\u00e7in, \u0130., and Durgun, M. (2020). Synthesis, Characterization, Inhibition Effects, and Molecular Docking Studies as Acetylcholinesterase, \u03b1-Glycosidase, and Carbonic Anhydrase Inhibitors of Novel Benzenesulfonamides Incorporating 1,3,5-Triazine Structural Motifs. Bioorg. Chem., 100.","DOI":"10.1016\/j.bioorg.2020.103897"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1124\/jpet.105.084145","article-title":"Role of Tyrosine Kinase Inhibitors in Cancer Therapy","volume":"315","author":"Arora","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.2174\/1871520618666180510113822","article-title":"Indazole Derivatives: Promising Anti-Tumor Agents","volume":"18","author":"Wan","year":"2018","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44247","DOI":"10.1039\/D0RA09198G","article-title":"Prescribed Drugs Containing Nitrogen Heterocycles: An Overview","volume":"10","author":"Heravi","year":"2020","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pandiyan, S., and Wang, L. (2024). In-Silico Design of Novel Potential HDAC Inhibitors from Indazole Derivatives Targeting Breast Cancer through QSAR, Molecular Docking and Pharmacokinetics Studies. Comput. Biol. Chem., 110.","DOI":"10.1016\/j.compbiolchem.2024.108035"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1080\/13543776.2018.1472240","article-title":"Indazole Derivatives and Their Therapeutic Applications: A Patent Review (2013\u20132017)","volume":"28","author":"Denya","year":"2018","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"839","DOI":"10.2174\/1871520620999200818160350","article-title":"Indazole as a Privileged Scaffold: The Derivatives and Their Therapeutic Applications","volume":"21","author":"Qin","year":"2021","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"869","DOI":"10.2174\/138955705774329564","article-title":"Pharmacological Properties of Indazole Derivatives: Recent Developments","volume":"5","author":"Cerecetto","year":"2005","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1007\/s00044-011-9631-3","article-title":"Indazole: A Medicinally Important Heterocyclic Moiety","volume":"21","author":"Thangadurai","year":"2012","journal-title":"Med. Chem. Res."},{"key":"ref_18","first-page":"439","article-title":"Pyrimidine-5-Carbonitriles: A Review of Available Synthetic Approaches and Biological Evaluation for Promising Compounds over the Last Decade","volume":"67","author":"Edris","year":"2024","journal-title":"Egypt. J. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.bmcl.2014.12.087","article-title":"Design and Synthesis of Novel 1,2,3-Triazole\u2013Pyrimidine\u2013Urea Hybrids as Potential Anticancer Agents","volume":"25","author":"Ma","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.bmcl.2008.09.067","article-title":"Synthesis and Biological Evaluation of Novel 2,4,5-Substituted Pyrimidine Derivatives for Anticancer Activity","volume":"19","author":"Xie","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s00044-019-02321-9","article-title":"Synthesis and Anticancer Activity Evaluation of Novel Oxacalix[2]Arene[2]Pyrimidine Derivatives","volume":"28","author":"Huang","year":"2019","journal-title":"Med. Chem. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ejmech.2016.04.068","article-title":"Design and synthesis of novel pyrazolo[1, 5-a]pyrimidine derivatives bearing nitrogen mustard moiety and evaluation of their antitumor activity in vitro and in vivo","volume":"119","author":"Zhao","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Al-Tuwaijri, H.M., Al-Abdullah, E.S., El-Rashedy, A.A., Ansari, S.A., Almomen, A., Alshibl, H.M., Haiba, M.E., and Alkahtani, H.M. (2023). New Indazol-Pyrimidine-Based Derivatives as Selective Anticancer Agents: Design, Synthesis, and In Silico Studies. Molecules, 28.","DOI":"10.3390\/molecules28093664"},{"key":"ref_24","first-page":"437","article-title":"Pazopanib (Votrient) in the management of renal cell cancer and soft tissue sarcomas","volume":"67","author":"Gennigens","year":"2012","journal-title":"Rev. Medicale De Liege"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/cbdd.12243","article-title":"Design, synthesis and biological evaluation of pazopanib derivatives as antitumor agents","volume":"83","author":"Jia","year":"2014","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_26","first-page":"739","article-title":"An efficient and practical synthesis of antibacterial linezolid","volume":"2009","author":"Zhang","year":"2009","journal-title":"J. Chem. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.molstruc.2019.05.081","article-title":"Efficient and Easy Synthesis of New Benzo[h]Chromene and Benzo[h]Quinoline Derivatives as a New Class of Cytotoxic Agents","volume":"1195","author":"Haiba","year":"2019","journal-title":"J. Mol. Struct."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mirzaei, S., Eisvand, F., Hadizadeh, F., Mosaffa, F., Ghasemi, A., and Ghodsi, R. (2020). Design, Synthesis and Biological Evaluation of Novel 5,6,7-Trimethoxy-N-Aryl-2-Styrylquinolin-4-Amines as Potential Anticancer Agents and Tubulin Polymerization Inhibitors. Bioorg. Chem., 98.","DOI":"10.1016\/j.bioorg.2020.103711"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8355","DOI":"10.1007\/s10570-021-04063-7","article-title":"Synthesis of Novel Heterocyclic Compounds Based on Dialdehyde Cellulose: Characterization, Antimicrobial, Antitumor Activity, Molecular Dynamics Simulation and Target Identification","volume":"28","author":"Hasanin","year":"2021","journal-title":"Cellulose"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s12013-018-0852-7","article-title":"Induced Mutation Proves a Potential Target for TB Therapy: A Molecular Dynamics Study on LprG","volume":"76","author":"Machaba","year":"2018","journal-title":"Cell Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"70681","DOI":"10.1371\/journal.pone.0070681","article-title":"Molecular Dynamics Study of Zn(A\u03b2) and Zn(A\u03b2)2","volume":"8","author":"Pan","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1080\/15216540500138246","article-title":"Conservation of Eubacterial Replicases","volume":"57","author":"Wijffels","year":"2005","journal-title":"IUBMB Life"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0022-2836(84)90231-6","article-title":"Solvent Accessible Surface Area and Excluded Volume in Proteins: Analytical Equations for Overlapping Spheres and Implications for the Hydrophobic Effect","volume":"178","author":"Richmond","year":"1984","journal-title":"J. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1021\/acs.jcim.7b00564","article-title":"Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations","volume":"57","author":"Cournia","year":"2017","journal-title":"J. Chem. Inf. Model."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/S1359-6446(04)03280-5","article-title":"Improving the Decision-Making Process in the Structural Modification of Drug Candidates: Enhancing Metabolic Stability","volume":"9","author":"Nassar","year":"2004","journal-title":"Drug Discov. Today"},{"key":"ref_36","first-page":"683","article-title":"Role and Significance of C-KIT Receptor Tyrosine Kinase in Cancer: A Review","volume":"22","author":"Sheikh","year":"2022","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1039\/C4CS00013G","article-title":"Guanidines: From Classical Approaches to Efficient Catalytic Syntheses","volume":"43","author":"Otero","year":"2014","journal-title":"Chem. Soc. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1542-2011.2011.00086.x","article-title":"Bacterial Vaginosis and Preterm Birth","volume":"56","year":"2011","journal-title":"J. Midwifery Women\u2019s Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31655","DOI":"10.1074\/jbc.M403319200","article-title":"Structural Basis for the Autoinhibition and STI-571 Inhibition of c-Kit Tyrosine Kinase","volume":"279","author":"Mol","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/prot.20660","article-title":"Very Fast Empirical Prediction and Rationalization of Protein pKa Values","volume":"61","author":"Li","year":"2005","journal-title":"Proteins"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"(2014). BETHANY HALFORD: Reflections on Chem Draw. Chem. Eng. News Arch., 92, 26\u201327.","DOI":"10.1021\/cen-09233-scitech1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: An Advanced Semantic Chemical Editor, Visualization, and Analysis Platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminform."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1758-2946-1-15","article-title":"Application of the PM6 Semi-Empirical Method to Modeling Proteins Enhances Docking Accuracy of AutoDock","volume":"1","author":"Bikadi","year":"2009","journal-title":"J. Cheminform."},{"key":"ref_46","unstructured":"Huey, R., and Molecular, G.M. (2006). Using Autodock with Autodocktools: A Tutorial, The Scripps Research Institute Molecular Graphics Laboratory."},{"key":"ref_47","first-page":"16391662","article-title":"Automated Docking Using a Lamarckian Genetic Algorithm and an Empirical Binding Free Energy Function","volume":"19","author":"Morris","year":"1639","journal-title":"J. Comput. Chem."},{"key":"ref_48","first-page":"37","article-title":"Molecular Dynamics Simulations: Advances and Applications","volume":"8","author":"Hospital","year":"2015","journal-title":"Adv. Appl. Bioinform. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1021\/acs.jcim.8b00462","article-title":"GPU-Accelerated Molecular Dynamics and Free Energy Methods in Amber18: Performance Enhancements and New Features","volume":"58","author":"Lee","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic Atom Type and Bond Type Perception in Molecular Mechanical Calculations","volume":"25","author":"Wang","year":"2006","journal-title":"J. Mol. Graph. Model."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular Dynamics with Coupling to an External Bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J. Chem. Phys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1021\/ci500161d","article-title":"OriginPro 9.1: Scientific Data Analysis and Graphing Software\u2014Software Review","volume":"54","author":"Seifert","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models","volume":"33","author":"Kollman","year":"2000","journal-title":"Acc. Chem. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1021\/ci4002475","article-title":"MMGBSA as a Tool to Understand the Binding Affinities of Filamin-Peptide Interactions","volume":"53","author":"Ylilauri","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"ref_56","unstructured":"Hayes, J.M., and Archontis, G. (2012). MM-GB(PB)SA Calculations of Protein-Ligand Binding Free Energies. Molecular Dynamics\u2014Studies of Synthetic and Biological Macromolecules, InTech Open."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the Performance of the MM\/PBSA and MM\/GBSA Methods. 1. The Accuracy of Binding Free Energy Calculations Based on Molecular Dynamics Simulations","volume":"51","author":"Hou","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1021\/ci300425v","article-title":"MM\/GBSA Binding Energy Prediction on the PDBbind Data Set: Successes, Failures, and Directions for Further Improvement","volume":"53","author":"Greenidge","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1021\/j100058a043","article-title":"Accurate Calculation of Hydration Free Energies Using Macroscopic Solvent Models","volume":"98","author":"Sitkoff","year":"1994","journal-title":"J. Phys. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/18\/3773\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:58Z","timestamp":1760035618000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/18\/3773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,17]]},"references-count":59,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["molecules30183773"],"URL":"https:\/\/doi.org\/10.3390\/molecules30183773","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2025,9,17]]}}}