{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T02:31:34Z","timestamp":1770604294038,"version":"3.49.0"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006565","name":"University of Johannesburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006565","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study details the synthesis, characterization, molecular docking and preliminary biological evaluation of a new heterocyclic compound, 2-((4-morpholino-1,2,5-thiadiazol-3-yl)oxy)benzaldehyde. This molecule was designed using an artificial intelligence (AI)-based molecular generative model. It was synthesized through a nucleophilic substitution between 3-chloro-4-morpholino-1,2,5-thiadiazole and 2-hydroxybenzaldehyde. Structural elucidation was performed using 1H NMR, 13C NMR, Elemental Analysis, and Single Crystal X-ray diffraction. AI-guided in silico predictions suggested promising pharmacophoric features and potential biological activity. Preliminary biological evaluation, primarily through anticancer assays, demonstrated moderate to significant activity, supporting further investigation. The findings therefore suggest that this AI-generated molecule could serve as a lead scaffold for developing drugs targeting cancer and other infectious diseases.<\/jats:p>","DOI":"10.3390\/molecules31030574","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:32:59Z","timestamp":1770395579000},"page":"574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis, Characterization, Molecular Docking, and Preliminary Biological Evaluation of 2-((4-Morpholino-1,2,5-thiadiazol-3-yl)oxy)benzaldehyde"],"prefix":"10.3390","volume":"31","author":[{"given":"Mokete","family":"Motente","sequence":"first","affiliation":[{"name":"Institute for Artificial Intelligent Systems, University of Johannesburg, P.O. Box 524, Johannesburg 2092, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uche A. K.","family":"Chude-Okonkwo","sequence":"additional","affiliation":[{"name":"Institute for Artificial Intelligent Systems, University of Johannesburg, P.O. Box 524, Johannesburg 2092, South Africa"},{"name":"Department of Chemical Sciences, University of Johannesburg, P.O. Box 524, Johannesburg 2092, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3390\/metabo2020303","article-title":"A historical overview of natural products in drug discovery","volume":"2","author":"Dias","year":"2012","journal-title":"Metabolites"},{"key":"ref_2","first-page":"52","article-title":"Leveraging Delaware\u2019s Public Health Resources to Mitigate Spread of Communicable Diseases in Congregate Settings","volume":"30","author":"Strmel","year":"2023","journal-title":"Dela. J. Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5714","DOI":"10.1021\/acs.jcim.0c00174","article-title":"The Synthesizability of Molecules Proposed by Generative Models","volume":"60","author":"Gao","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1758-2946-1-8","article-title":"Estimation of Synthetic Accessibility Score of Drug-Like Molecules Based on Molecular Complexity and Fragment Contributions","volume":"1","author":"Ertl","year":"2009","journal-title":"J. Cheminform."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.gendis.2022.02.007","article-title":"Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics","volume":"10","author":"Anand","year":"2022","journal-title":"Genes Dis."},{"key":"ref_6","first-page":"427","article-title":"Targeted cancer therapies","volume":"9","author":"Aggarwal","year":"2010","journal-title":"Nat. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"928901","DOI":"10.5402\/2012\/928901","article-title":"Synthesis, urease inhibition, antioxidant, antibacterial, and molecular docking studies of 1,3,4-oxadiazole derivatives","volume":"2012","author":"Hanif","year":"2012","journal-title":"ISRN Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1016\/j.ejmech.2010.07.031","article-title":"Synthesis of novel sulfanilamide-derived 1,2,3-triazoles and their evaluation for antibacterial and antifungal activities","volume":"45","author":"Wang","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","first-page":"117","article-title":"Preludin (phenmetrazine) in the treatment of obesity","volume":"15","author":"Martel","year":"1957","journal-title":"Can. Med. Assoc. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/med.21634","article-title":"Morpholine as a privileged structure: A review on the medicinal chemistry and pharmacological activity of morpholine-containing bioactive molecules","volume":"40","author":"Kourounakis","year":"2020","journal-title":"Med. Res. Rev."},{"key":"ref_11","unstructured":"Swathi, G. (2014). UGC-SERO\u2014Sponsored National Conference on \u201cBiodiversity, Environment Hazards\u2014Therapeutic Approaches and Drug Design\u201d, Academic Press."},{"key":"ref_12","first-page":"3750","article-title":"Pyran copolymer as an effective adjuvant to chemotherapy against a murine leukemia and solid tumor","volume":"35","author":"Mohr","year":"1975","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/s41598-024-81294-1","article-title":"New thiazole derivative as a potential anticancer and topoisomerase II inhibitor","volume":"15","author":"Shosha","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"71","DOI":"10.5578\/mb.20239906","article-title":"Evaluation of the Ex Vivo Cultivation Potential of Trypanosoma cruzi, Leishmania tropica, and Toxoplasma gondii Parasites in J774, Vero, and HeLa Cell Lines","volume":"57","author":"Yereli","year":"2023","journal-title":"Mikrobiyol. Bul."},{"key":"ref_15","first-page":"733","article-title":"Antiprotozoal activity of auranofin on Trypanosoma cruzi, Leishmania tropica and Toxoplasma gondii in vitro and ex vivo study","volume":"3","author":"Yereli","year":"2023","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chmovzh, T.N., Kudryashev, T.A., Alekhina, D.A., and Rakitin, O.A. (2023). Palladium-Catalyzed Direct (Het)arylation Reactions of Benzo [1,2-d:4,5-d\u2032]bis([1,2,3]thiadiazole) and 4,8-Dibromobenzo[1,2-d:4,5-d\u2032]bis([1,2,3]thiadiazole). Molecules, 28.","DOI":"10.3390\/molecules28093977"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6907","DOI":"10.1021\/acs.orglett.3c02673","article-title":"The Photochemical Mediated Ring Contraction of 4H-1,2,6- Thiadiazines To Afford 1,2,5Thiadiazol-3(2H)-one 1-Oxides","volume":"25","author":"Broumidis","year":"2023","journal-title":"Org. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112016","DOI":"10.1016\/j.ejmech.2019.112016","article-title":"Thiazole-containing compounds as therapeutic targets for cancer therapy","volume":"188","author":"Sharma","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/S0223-5234(97)86181-8","article-title":"2,4-Disubstituted thiazoles II. A novel class of antitumor agents, synthesis and biological evaluation","volume":"31","year":"1996","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1080\/00397911.2018.1557687","article-title":"Rapid access to novel 2-alkylthiopyrimidine derivatives and attempt of their Tacrine analogs synthesis","volume":"49","author":"Derabli","year":"2019","journal-title":"Synth. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yu, H., Zhang, W., Yu, Q., Huang, F.P., Bian, H.D., and Liang, H. (2017). Ni(II) Complexes with Schiff Base Ligands: Preparation, Characterization, DNA\/Protein Interaction and Cytotoxicity Studies. Molecules, 22.","DOI":"10.3390\/molecules22101772"},{"key":"ref_22","first-page":"714","article-title":"Synthesis, characterization and cytotoxic activity of new salicylaldehyde benzoylhydrazone derivatives as potential anti-proliferative agents","volume":"61","author":"Halachev","year":"2011","journal-title":"Arzneimittelforschung"},{"key":"ref_23","first-page":"233","article-title":"Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation","volume":"15","author":"Momekov","year":"2017","journal-title":"J. Appl. Biomed."},{"key":"ref_24","first-page":"27","article-title":"Crystal structure of 2-((4-morpholino-1,2,5-thiadiazol-3-yl)oxy)benzaldehyde, C13H13O3N3S","volume":"241","author":"Motente","year":"2025","journal-title":"Z. Kristallogr.\u2014N. Cryst. Struct."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/jnci\/83.11.757","article-title":"Feasibility of a High-Flux Anticancer Drug Screen Using a Diverse Panel of Cultured Human Tumor Cell Lines","volume":"83","author":"Monks","year":"1991","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/cmdc.201900682","article-title":"Morpholine as a Scaffold in Medicinal Chemistry: An Update on Synthetic Strategies","volume":"15","author":"Tzara","year":"2020","journal-title":"Chem. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"128027","DOI":"10.1016\/j.bmcl.2021.128027","article-title":"A facile method for vancomycin C-terminus functionalization and derivatization through hydrazide","volume":"41","author":"Hu","year":"2021","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9412","DOI":"10.1039\/D2DT00793B","article-title":"Silver(I) Complexes Bearing Heterocyclic Thioamide Ligands with NH2 and CF3 Substituents: Effect of Ligand Group Substitution on Antibacterial and Anticancer Properties","volume":"51","author":"Varna","year":"2022","journal-title":"Dalton Trans."},{"key":"ref_29","first-page":"832","article-title":"From Hybrids to New Scaffolds: The Latest Medicinal Chemistry Goals in Multi-Target Directed Ligands for Alzheimer\u2019s Disease","volume":"19","author":"Mallea","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Indelicato, S., Bongiorno, D., Mauro, M., and Cascioferro, S. (2025). Recent Developments of 1,3,4-Thiadiazole Compounds as Anticancer Agents. Pharmaceuticals, 18.","DOI":"10.3390\/ph18040580"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, M., Zhang, X., Lu, D., Luo, H., Zhou, Z., Qin, X., Wu, W., and Zhang, G. (2021). Synthesis and Bioactivities of Novel Galactoside Derivatives Containing 1,3,4-Thiadiazole Moiety. Front. Chem., 9.","DOI":"10.3389\/fchem.2021.645876"},{"key":"ref_32","unstructured":"(2004). Bruker SAINT-Plus (Version 7.12) and SADABS (Version 2004\/1), Bruker AXS Inc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"A short history of SHELX","volume":"A64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1107\/S0021889808042726","article-title":"OLEX2: A complete structure solution, refinement and analysis program","volume":"42","author":"Dolomanov","year":"2009","journal-title":"J. Appl. Cryst."},{"key":"ref_35","unstructured":"Brandenburg, K. (DIAMOND. Visual Crystal Structure Information System, 2005). DIAMOND. Visual Crystal Structure Information System, Version 3.0c."},{"key":"ref_36","unstructured":"ATCC (2025, December 10). Cell Lines by Tissue\/Organ: American Type Culture Collection. Available online: https:\/\/www.atcc.org."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/jnci\/51.5.1409","article-title":"A human cell line from a pleural effusion derived from a breast carcinoma","volume":"51","author":"Soule","year":"1973","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_38","first-page":"16","article-title":"Establishment and characterization of a human prostatic carcinoma cell line (PC-3)","volume":"17","author":"Kaighn","year":"1979","journal-title":"Investig. Urol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/227168a0","article-title":"Characteristics of a Human Diploid Cell Designated MRC-5","volume":"227","author":"Jacobs","year":"1970","journal-title":"Nature"},{"key":"ref_40","unstructured":"Freshney, R.I. (2021). Culture of Animal Cells: A Manual of Basic Technique and Specialized Applications, Wiley-Blackwell. [8th ed.]."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid Colorimetric Assay for Cellular Growth and Survival","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Method"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Motulsky, H.J., and Christopoulos, A. (2004). Fitting Models to Biological Data Using Linear and Nonlinear Regression: A Practical Guide to Curve Fitting, Oxford University Press.","DOI":"10.1093\/oso\/9780195171792.001.0001"},{"key":"ref_43","unstructured":"GraphPad Software (2025, October 18). GraphPad Prism Version 8.0 for Windows, Available online: https:\/\/www.graphpad.com."},{"key":"ref_44","unstructured":"Schr\u00f6dinger LLC (Schr\u00f6dinger Suite Release 2025-3, 2025). Schr\u00f6dinger Suite Release 2025-3."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D437","DOI":"10.1093\/nar\/gkaa1038","article-title":"RCSB Protein Data Bank: Powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences","volume":"49","author":"Burley","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"Comput.-Aided Mol. Des."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4291","DOI":"10.1021\/acs.jctc.1c00302","article-title":"OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space","volume":"17","author":"Harder","year":"2021","journal-title":"J. Chem. Theory Comput."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra Precision Glide:\u2009 Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein\u2212Ligand Complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/3\/574\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T05:13:58Z","timestamp":1770527638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/3\/574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["molecules31030574"],"URL":"https:\/\/doi.org\/10.3390\/molecules31030574","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}