{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:54:48Z","timestamp":1778028888925,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria","award":["BG-RRP-2.004-0004-C01."],"award-info":[{"award-number":["BG-RRP-2.004-0004-C01."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Some studies performed in our laboratory on pyrrole and its derivatives pointed towards the enrichment of the evaluations of these promising chemical structures for the potential treatment of neurodegenerative conditions in general and Parkinson\u2019s disease in particular. A classical Paal-Knorr cyclization approach is applied to synthesize the basic hydrazine used for the formation of the designed series of hydrazones (15a\u201315g). The potential neurotoxic and neuroprotective effects of the newly synthesized derivatives were investigated in vitro using different models of induced oxidative stress at three subcellular levels (rat brain synaptosomes, mitochondria, and microsomes). The results identified as the least neurotoxic molecules, 15a, 15d, and 15f applied at a concentration of 100 \u00b5M to the isolated fractions. In addition, the highest statistically significant neuroprotection was observed for 15a and 15d at a concentration of 100 \u00b5M using three different injury models on subcellular fractions, including 6-hydroxydopamine in rat brain synaptosomes, tert-butyl hydroperoxide in brain mitochondria, and non-enzyme-induced lipid peroxidation in brain microsomes. The hMAOA\/MAOB inhibitory activity of the new compounds was studied at a concentration of 1 \u00b5M. The lack of a statistically significant hMAOA inhibitory effect was observed for all tested compounds, except for 15f, which showed 40% inhibitory activity. The most prominent statistically significant hMAOB inhibitory effect was determined for 15a, 15d, and 15f, comparable to that of selegiline. The corresponding selectivity index defined 15f as a non-selective MAO inhibitor and all other new hydrazones as selective hMAOB inhibitors, with 15d indicating the highest selectivity index of &gt;471. The most active and least toxic representative (15d) was evaluated in vivo on Rotenone based model of Parkinson\u2019s disease. The results revealed no microscopically visible alterations in the ganglion and glial cells in the animals treated with rotenone in combination with 15d.<\/jats:p>","DOI":"10.3390\/molecules30153154","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:05:47Z","timestamp":1753711547000},"page":"3154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Classical Paal-Knorr Cyclization for Synthesis of Pyrrole-Based Aryl Hydrazones and In Vitro\/In Vivo Evaluation on Pharmacological Models of Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-5002","authenticated-orcid":false,"given":"Maya","family":"Georgieva","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Sharkov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5885-7213","authenticated-orcid":false,"given":"Emilio","family":"Mateev","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1708-1287","authenticated-orcid":false,"given":"Diana","family":"Tzankova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgi","family":"Popov","sequence":"additional","affiliation":[{"name":"Department of Internal Non-Communicable Diseases, Pathology and Pharmacology, Faculty of Veterinary Medicine, University of Forestry, 10 St. Kliment Ohridski Blvd., 1797 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9306-3665","authenticated-orcid":false,"given":"Vasil","family":"Manov","sequence":"additional","affiliation":[{"name":"Department of Internal Non-Communicable Diseases, Pathology and Pharmacology, Faculty of Veterinary Medicine, University of Forestry, 10 St. Kliment Ohridski Blvd., 1797 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1695-8454","authenticated-orcid":false,"given":"Alexander","family":"Zlatkov","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-9053","authenticated-orcid":false,"given":"Rumyana","family":"Simeonova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-0870","authenticated-orcid":false,"given":"Magdalena","family":"Kondeva-Burdina","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","unstructured":"Zafar, S., and Yaddanapudi, S.S. (2023). Parkinson Disease. StatPearls, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/B978-0-323-85538-9.00015-8","article-title":"Biomarkers of diagnosis, prognosis, pathogenesis, response to therapy: Convergence or divergence? Lessons from Alzheimer\u2019s disease and synucleinopathies","volume":"192","author":"Sensi","year":"2023","journal-title":"Handb. Clin. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s11910-017-0738-x","article-title":"Subtypes of Parkinson\u2019s disease: What do they tell us about disease progression?","volume":"17","author":"Fereshtehnejad","year":"2017","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1001\/jamaneurol.2013.6233","article-title":"Parkinson disease subtypes","volume":"71","author":"Thenganatt","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1093\/brain\/awx118","article-title":"Clinical criteria for subtyping Parkinson\u2019s disease: Biomarkers and longitudinal progression","volume":"140","author":"Fereshtehnejad","year":"2017","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1136\/jnnp-2018-318337","article-title":"Developing and validating Parkinson\u2019s disease subtypes and their motor and cognitive progression","volume":"89","author":"Lawton","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/mds.23346","article-title":"Clinical subtypes of Parkinson\u2019s disease","volume":"26","author":"Colas","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and Treatment of Parkinson Disease: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1002\/mds.27372","article-title":"International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson\u2019s disease","volume":"33","author":"Fox","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"344","DOI":"10.31925\/farmacia.2022.2.21","article-title":"Design, synthesis, biological evaluation and molecular docking of pyrrole-based compounds as antioxidant and MAO-B inhibitory agents","volume":"70","author":"Mateev","year":"2022","journal-title":"Farmacia"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Georgieva, M., Mateev, E., Valkova, I., Kuteva, H., Tzankova, D., Stefanova, D., Yordanov, Y., Lybomirova, K., Zlatkov, A., and Tzankova, V. (2024). Neurotoxicity, Neuroprotection, In Vitro MAOA\/MAOB Inhibitory Activity Assessment, Molecular Docking, and Permeability Assay Studies of Newly Synthesized Hydrazones Containing a Pyrrole Ring. Molecules, 29.","DOI":"10.3390\/molecules29184338"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kondeva-Burdina, M., Mateev, E., Angelov, B., Tzankova, V., and Georgieva, M. (2022). In Silico Evaluation and In Vitro Determination of Neuroprotective and MAO-B Inhibitory Effects of Pyrrole-Based Hydrazones: A Therapeutic Approach to Parkinson\u2019s Disease. Molecules, 27.","DOI":"10.3390\/molecules27238485"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mateev, E., Karatchobanov, V., Dedja, M., Diamantakos, K., Mateeva, A., Muhammed, M.T., Irfan, A., Kondeva-Burdina, M., Valkova, I., and Georgieva, M. (2024). Novel Pyrrole Derivatives as Multi-Target Agents for the Treatment of Alzheimer\u2019s Disease: Microwave-Assisted Synthesis, In Silico Studies and Biological Evaluation. Pharmaceuticals, 17.","DOI":"10.3390\/ph17091171"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6924","DOI":"10.1021\/jo00024a040","article-title":"Intermediates in the Paal-Knorr synthesis of pyrroles","volume":"56","author":"Amarnath","year":"1991","journal-title":"J. Org. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"T\u00f6r\u00f6k, B., Sch\u00e4fer, C., and Kokel, A. (2021). Chapter 3.8\u2014Ring transformations by heterogeneous catalysis. Heterogeneous Catalysis in Sustainable Synthesis, Elsevier. [1st ed.].","DOI":"10.1016\/B978-0-12-817825-6.00011-2"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"430","DOI":"10.2174\/157018010791306588","article-title":"Pyrrole-based hydrazones synthesized and evaluated in vitro as potential tuberculostatics","volume":"7","author":"Bijev","year":"2010","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_17","first-page":"3","article-title":"Synthesis and comparative study of tuberculostatic activity of pyrrole-based hydra-zones related to structural variations","volume":"52","author":"Georgieva","year":"2010","journal-title":"Pharmacia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/B978-0-08-096805-6.00006-1","article-title":"Chapter 5.2\u2014Five-Membered Ring Systems: Pyrroles and Benzo Analogs","volume":"Volume 23","author":"Gribble","year":"2011","journal-title":"Progress in Heterocyclic Chemistry"},{"key":"ref_19","first-page":"924","article-title":"A New Facile Approach to Isoindole and Pyrrole Derivatives","volume":"6","author":"Yasmin","year":"2010","journal-title":"Synlett"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4512","DOI":"10.1016\/j.tetlet.2010.06.092","article-title":"CuCl-catalyzed cycloaddition of 1,3-butadiynes with primary amines: An atom-economic process for synthesis of 1,2,5-trisubsituted pyrroles","volume":"51","author":"Zheng","year":"2010","journal-title":"Tetrahedron Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1021\/ol1008685","article-title":"Access to 2,5-diamidopyrroles and 2,5-diamidofurans by Au(I)-catalyzed double hydroamination or hydration of 1,3-diynes","volume":"12","author":"Kramer","year":"2010","journal-title":"Org. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8032","DOI":"10.1039\/c0cc02357d","article-title":"Gold(I)\/Zn(II) catalyzed tandem hydroamination\/annulation reaction of 4-yne-nitriles","volume":"46","author":"Demir","year":"2010","journal-title":"Chem. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Huo, J., He, G., Chen, W., Hu, X., Deng, Q., and Chen, D. (2019). A minireview of hydroamination catalysis: Alkene and alkyne substrate selective, metal complex design. BMC Chem., 13.","DOI":"10.1186\/s13065-019-0606-7"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/ejoc.200300485","article-title":"Coupling Reactions of 1,4-Dicuprio-1,3-dienes: Formation of Carbocycles","volume":"2004","author":"Chen","year":"2004","journal-title":"Eur. J. Org. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2478\/acph-2020-0026","article-title":"Synthesis, in vitro safety and antioxidant activity of new pyrrole hydrazones","volume":"70","author":"Tzankova","year":"2020","journal-title":"Acta Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13321-015-0067-5","article-title":"Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets","volume":"7","author":"Feinstein","year":"2015","journal-title":"J. Cheminform."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1111\/bcp.13651","article-title":"A multiple treatment comparison meta-analysis of monoamine oxidase type B inhibitors for Parkinson\u2019s disease","volume":"84","author":"Binde","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s00228-020-02961-6","article-title":"Comparative effectiveness of dopamine agonists and monoamine oxidase type-B inhibitors for Parkinson\u2019s disease: A multiple treatment comparison meta-analysis","volume":"76","author":"Binde","year":"2020","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_29","first-page":"100136","article-title":"Parkinson\u2019s disease, treatment choice and survival over time","volume":"6","author":"Tvete","year":"2022","journal-title":"Clin. Park. Relat. Disord."},{"key":"ref_30","first-page":"9952743","article-title":"Time until Need for Levodopa among New Users of Dopamine Agonists or MAO-B Inhibitors","volume":"2021","author":"Binde","year":"2021","journal-title":"Park. Dis."},{"key":"ref_31","first-page":"e75647","article-title":"Parkinson\u2019s Disease: Current Treatment Modalities and Emerging Therapies","volume":"16","author":"Alotaibi","year":"2024","journal-title":"Cureus"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.chembiol.2025.01.001","article-title":"SynPull: An advanced method for studying neurodegeneration-related aggregates in synaptosomes using super-resolution microscopy","volume":"32","author":"Kedia","year":"2025","journal-title":"Cell Chem. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00292","DOI":"10.1016\/j.neurot.2023.10.002","article-title":"Mitochondrial dysfunction in neurodegenerative disorders","volume":"21","author":"Klemmensen","year":"2024","journal-title":"Neurotherapeutics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1136\/jnnp-2013-306787","article-title":"Impulse control disorder in patients with Parkinson\u2019s disease under dopamine agonist therapy: A multicentre study","volume":"85","author":"Barcenas","year":"2014","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1001\/archneurol.2009.294","article-title":"Dopamine agonist withdrawal syndrome in Parkinson disease","volume":"67","author":"Rabinak","year":"2010","journal-title":"Arch. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1136\/jnnp-2012-302684","article-title":"Clinical features of dopamine agonist withdrawal syndrome in a movement disorders clinic","volume":"84","author":"Pondal","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2238","DOI":"10.1212\/WNL.0000000000006643","article-title":"Levodopa-induced dyskinesia in Parkinson disease: A population-based cohort study","volume":"91","author":"Turcano","year":"2018","journal-title":"Neurology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1111\/j.1471-4159.1983.tb08123.x","article-title":"The metabolism of dopamine by both forms of monoamine oxidase in the rat brain and its inhibition by cimoxatone","volume":"40","author":"Fowler","year":"1983","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/BF02251224","article-title":"In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal L-DOPA and dopamine metabolism","volume":"10","author":"Brannan","year":"1995","journal-title":"J. Neural. Transm. Park Dis. Dement. Sect."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Nam, M.-H., Sa, M., Ju, Y.H., Park, M.G., and Lee, C.J. (2022). Revisiting the Role of Astrocytic MAOB in Parkinson\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084453"},{"key":"ref_41","first-page":"461","article-title":"The Role of Oxidative Stress in Parkinson\u2019s Disease","volume":"3","author":"Dias","year":"2013","journal-title":"J. Park. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"67","DOI":"10.33549\/physiolres.930578","article-title":"Tert-butyl hydroperoxide selectively inhibits mitochondrial respiratory-chain enzymes in isolated rat hepatocytes","volume":"54","author":"Drahota","year":"2005","journal-title":"Physiol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/0891-5849(95)00062-3","article-title":"Cellular injury induced by oxidative stress is mediated through lysosomal damage","volume":"19","author":"Brunk","year":"1995","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1042\/bj3040707","article-title":"Mitochondrial metabolism of a hydroperoxide to free radicals in human endothelial cells: An electron spin resonance spin-trapping investigation","volume":"304","author":"Burkitt","year":"1994","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.1751-1097.1993.tb09550.x","article-title":"Photodynamic effects of new silicon phthalocyanines: In vitro studies utilizing rat hepatic microsomes and human erythrocyte ghosts as model membrane sources","volume":"58","author":"Zaidi","year":"1993","journal-title":"Photochem. Photobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"506","DOI":"10.2174\/157018006778194790","article-title":"New heterocyclic hydrazones in the search for antitubercular agents: Synthesis and in vitro evaluations","volume":"3","author":"Bijev","year":"2006","journal-title":"Lett. Drug Des. Dis."},{"key":"ref_47","first-page":"1099","article-title":"Validation through re-docking, cross-docking and ligand enrichment in various well-resoluted mao-b receptors","volume":"13","author":"Mateev","year":"2022","journal-title":"Int. J. Pharmaceut. Sci. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1046\/j.1471-4159.1994.62041586.x","article-title":"Subcellular fractionation on Percoll gradient of mossy fiber synaptosomes: Morphological and biochemical characterization in control and degranulated rat hippocampus","volume":"62","author":"Taupin","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0161-813X(02)00093-1","article-title":"Induction of GADD45 and GADD153 in neuroblastoma cells by dopamine-induced toxicity","volume":"23","author":"Stokes","year":"2002","journal-title":"Neurotoxicology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/jnr.10193","article-title":"\u03b2-Amyloid peptide induces ultrastructural changes in synaptosomes and potentiates mitochondrial dysfunction in the presence of ryanodine","volume":"68","author":"Ferrera","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/0003-9861(71)90334-1","article-title":"Reaction of protein disulfide groups with Ellman\u2019s reagent: A case study of the number of sulfhydryl and disulfide groups in Aspergillus oryzae \u03b1-amylase, papain, and lysozyme","volume":"147","author":"Robyt","year":"1971","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1046\/j.1471-4159.2000.0750141.x","article-title":"trans-Resveratrol protects embryonic mesencephalic cells from tert-butyl hydroperoxide: Electron paramagnetic resonance spin trapping evidence for a radical scavenging mechanism","volume":"75","author":"Karlsson","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7688","DOI":"10.1007\/s11356-018-04119-5","article-title":"Th ameliorative effect of quercetin on bisphenol A-induced toxicity in mitochondria isolated from rats","volume":"26","author":"Shirani","year":"2019","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/0003-2697(90)90461-H","article-title":"Preparation of brain microsomes with cytochrome P450 activity using calcium aggregation method","volume":"187","author":"Ravindranath","year":"1990","journal-title":"Anal. Biochem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/0006-291X(86)91029-6","article-title":"A new potent inhibitor of lipid peroxidation in vitro and in vivo, the hepatoprotective drug anisyldithiolthione","volume":"135","author":"Mansuy","year":"1986","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","first-page":"82","article-title":"Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase\/monoamine oxidase inhibitors for the potential treatment of Alzheimer\u2019s disease","volume":"21","author":"Esteban","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_57","unstructured":"Bancroft, J., and Gamble, M. (2008). Theory and Practice of Histological Techniques, Churchill Livingstone (Elsevier Health Sciences). [6th ed.]."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/15\/3154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:17:21Z","timestamp":1760033841000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/15\/3154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":57,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["molecules30153154"],"URL":"https:\/\/doi.org\/10.3390\/molecules30153154","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]}}}