{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:21:40Z","timestamp":1779909700063,"version":"3.53.1"},"reference-count":72,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic reprogramming in cancer is considered to be one of the most important hallmarks to drive proliferation, angiogenesis, and invasion. AMP-activated protein kinase activation is one of the established mechanisms for metformin\u2019s anti-cancer actions. However, it has been suggested that metformin may exert antitumoral effects by the modulation of other master regulators of cellular energy. Here, based on structural and physicochemical criteria, we tested the hypothesis that metformin may act as an antagonist of L-arginine metabolism and other related metabolic pathways. First, we created a database containing different L-arginine-related metabolites and biguanides. After that, comparisons of structural and physicochemical properties were performed employing different cheminformatic tools. Finally, we performed molecular docking simulations using AutoDock 4.2 to compare the affinities and binding modes of biguanides and L-arginine-related metabolites against their corresponding targets. Our results showed that biguanides, especially metformin and buformin, exhibited a moderate-to-high similarity to the metabolites belonging to the urea cycle, polyamine metabolism, and creatine biosynthesis. The predicted affinities and binding modes for biguanides displayed good concordance with those obtained for some L-arginine-related metabolites, including L-arginine and creatine. In conclusion, metabolic reprogramming in cancer cells by metformin and biguanides may be also driven by metabolic disruption of L-arginine and structurally related compounds.<\/jats:p>","DOI":"10.3390\/ijms24065316","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T05:02:17Z","timestamp":1678424537000},"page":"5316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Metformin May Alter the Metabolic Reprogramming in Cancer Cells by Disrupting the L-Arginine Metabolism: A Preliminary Computational Study"],"prefix":"10.3390","volume":"24","author":[{"given":"Bryan Alejandro","family":"Espinosa-Rodriguez","sequence":"first","affiliation":[{"name":"Universidad Autonoma de Nuevo Leon, School of Chemistry, Laboratory of Molecular Pharmacology and Biological Models, San Nicolas de los Garza 64570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Trevi\u00f1o-Almaguer","sequence":"additional","affiliation":[{"name":"Universidad Autonoma de Nuevo Leon, School of Chemistry, Laboratory of Molecular Pharmacology and Biological Models, San Nicolas de los Garza 64570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8944-9298","authenticated-orcid":false,"given":"Pilar","family":"Carranza-Rosales","sequence":"additional","affiliation":[{"name":"Centro de Investigacion Biomedica del Noreste, Laboratory of Cell Biology, Instituto Mexicano del Seguro Social, Monterrey 66720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica Azucena","family":"Ramirez-Cabrera","sequence":"additional","affiliation":[{"name":"Universidad Autonoma de Nuevo Leon, School of Chemistry, Laboratory of Molecular Pharmacology and Biological Models, San Nicolas de los Garza 64570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7840-7981","authenticated-orcid":false,"given":"Karla","family":"Ramirez-Estrada","sequence":"additional","affiliation":[{"name":"Universidad Autonoma de Nuevo Leon, School of Chemistry, Laboratory of Molecular Pharmacology and Biological Models, San Nicolas de los Garza 64570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0983-7558","authenticated-orcid":false,"given":"Eder Ubaldo","family":"Arredondo-Espinoza","sequence":"additional","affiliation":[{"name":"Universidad Autonoma de Nuevo Leon, School of Chemistry, Laboratory of Molecular Pharmacology and Biological Models, San Nicolas de los Garza 64570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1164-4544","authenticated-orcid":false,"given":"Luis Fernando","family":"Mendez-Lopez","sequence":"additional","affiliation":[{"name":"Universidad Autonoma de Nuevo Leon, School of Public Health and Nutrition, Center for Research on Nutrition and Public Health, Monterrey 66460, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaias","family":"Balderas-Renteria","sequence":"additional","affiliation":[{"name":"Universidad Autonoma de Nuevo Leon, School of Chemistry, Laboratory of Molecular Pharmacology and Biological Models, San Nicolas de los Garza 64570, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Weinberg","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, C.L., Hsu, S.C., Ann, D.K., Yen, Y., and Kung, H.J. 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