{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T21:57:12Z","timestamp":1767995832462,"version":"3.49.0"},"reference-count":118,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"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 rising tide of antibacterial drug resistance has given rise to the virtual elimination of numerous erstwhile antibiotics, intensifying the urgent demand for novel agents. A number of drugs have been found to possess potent antimicrobial action during the past several years and have the potential to supplement or even replace the antibiotics. Many of these \u2018non-antibiotics\u2019, as they are referred to, belong to the widely used class of neuroleptics, the phenothiazines. Another chemically and pharmacologically related class is the thioxanthenes, differing in that the aromatic N of the central phenothiazine ring has been replaced by a C atom. Such \u201ccarbon-analogues\u201d were primarily synthesized with the hope that these would be devoid of some of the toxic effects of phenothiazines. Intensive studies on syntheses, as well as chemical and pharmacological properties of thioxanthenes, were initiated in the late 1950s. Although a rather close parallelism with respect to structure activity relationships could be observed between phenothiazines and thioxanthenes; several thioxanthenes were synthesized in pharmaceutical industries and applied for human use as neuroleptics. Antibacterial activities of thioxanthenes came to be recognized in the early 1980s in Europe. During the following years, many of these drugs were found not only to be antibacterial agents but also to possess anti-mycobacterial, antiviral (including anti-HIV and anti-SARS-CoV-2) and anti-parasitic properties. Thus, this group of drugs, which has an inhibitory effect on the growth of a wide variety of microorganisms, needs to be explored for syntheses of novel antimicrobial agents. The purpose of this review is to summarize the neuroleptic and antimicrobial properties of this exciting group of bioactive molecules with a goal of identifying potential structures worthy of future exploration.<\/jats:p>","DOI":"10.3390\/molecules27010196","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Double-Edged Sword: Thioxanthenes Act on Both the Mind and the Microbiome"],"prefix":"10.3390","volume":"27","author":[{"given":"Marianne","family":"Poulsen","sequence":"first","affiliation":[{"name":"Memphys Center for Biomembrane Physics, Department of Physics and Chemistry, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujata","family":"Dastidar","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Kolkata 700154, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debalina","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Kolkata 700154, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shauroseni","family":"Palchoudhuri","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Kolkata 700154, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jette","family":"Kristiansen","sequence":"additional","affiliation":[{"name":"Memphys Center for Biomembrane Physics, Department of Physics and Chemistry, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Fey","sequence":"additional","affiliation":[{"name":"CelVivo ApS, 5220 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ahmed, U., Jones, H., and Adams, C.E. (2010). Chlorpromazine for psychosis induced aggression or agitation. Cochrane Database Syst. Rev., 4.","DOI":"10.1002\/14651858.CD007445.pub2"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1080\/0964704X.2012.664087","article-title":"The Chlorpromazine Enigma","volume":"22","author":"Baumeister","year":"2013","journal-title":"J. Hist. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1440-1819.2009.02033.x","article-title":"Relationship of psychopathological symptoms and cognitive function to subjective quality of life in patients with chronic schizophrenia","volume":"64","author":"Tomida","year":"2010","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.neubiorev.2017.02.006","article-title":"Neuronal and molecular effects of cannabidiol on the mesolimbic dopamine system: Implications for novel schizophrenia treatments","volume":"75","author":"Renard","year":"2017","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_5","first-page":"42","article-title":"Rediscovering clozapine: After a turbulent history, current guidance on initiating and monitoring","volume":"15","author":"Newman","year":"2016","journal-title":"Curr. Psychiatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1146\/annurev-med-050911-161504","article-title":"Update on typical and atypical antipsychotic drugs","volume":"64","author":"Meltzer","year":"2013","journal-title":"Annu. Rev. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s00213-012-2699-8","article-title":"Flupentixol: Relevance of stereoselective therapeutic drug monitoring","volume":"221","author":"Baumann","year":"2012","journal-title":"Psychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Behere, P.B., Das, A., and Behere, A.P. (2019). Antipsychotics. Clinical Psychopharmacology, Springer.","DOI":"10.1007\/978-981-13-2092-7"},{"key":"ref_9","unstructured":"Schatzberg, A.F., and Nemeroff, C.B. (2013). Classic Antipsychotic Medications. Essentials of Clinical Psychopharmacology, American Psychiatric Publishing Inc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1192\/bjp.bp.110.083766","article-title":"The rise and fall of the atypical antipsychotics","volume":"199","author":"Kendall","year":"2011","journal-title":"Br. J. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/BF00407980","article-title":"Chlorprothixene (\u201cTruxal\u201d) compared to chlorpromazine","volume":"2","author":"Remvig","year":"1961","journal-title":"Psychopharmacologia"},{"key":"ref_12","first-page":"148","article-title":"Extrapyramidal symptoms associated with antidepressants\u2014A review of the literature and an analysis of spontaneous reports","volume":"22","author":"Madhusoodanan","year":"2010","journal-title":"Ann. Clin. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.4088\/JCP.13078tx4c","article-title":"Mechanism of Action of Antipsychotic Medications","volume":"75","author":"Correll","year":"2014","journal-title":"J. Clin. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"s13","DOI":"10.1192\/bjp.195.52.s13","article-title":"Psychopharmacology and adverse effects of antipsychotic long-acting injections: A review","volume":"195","author":"Taylor","year":"2009","journal-title":"Br. J. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1177\/0269881113478281","article-title":"Comparison of the anti-dopamine D2 and anti-serotonin 5-HT 2A activities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof","volume":"27","author":"Suzuki","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4103\/2231-0738.150074","article-title":"Chlorpromazine-induced severe exfoliative photoallergic reaction","volume":"5","author":"Dhanasekaran","year":"2015","journal-title":"Int. J. Nutr. Pharm. Neurol. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/j.1600-0447.1971.tb03695.x","article-title":"Eye changes in connection with neuroleptic treatment especially concerning phenothiazines and thioxanthenes","volume":"47","author":"Edler","year":"1971","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_18","first-page":"90","article-title":"First Generation Antipsychotics: Pharmacokinetics, Pharmacodynamics, Therapeutic Effects and Side effects: A review","volume":"4","author":"Ayano","year":"2016","journal-title":"RRJChem"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Haddad, P., Lambert, T., and Lauriello, J. (2011). Pharmacology of antipsychotic long-acting injections. Antipsychotic Long-Acting Injections, Oxford University Press Inc.","DOI":"10.1093\/med\/9780199586042.001.0001"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.2174\/1568026616666160608084834","article-title":"Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future","volume":"16","author":"Li","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.cap.2017.08.020","article-title":"A theoretical study of the structural and electronic properties of trans and cis structures of chlorprothixene as a nano-drug","volume":"17","author":"Novir","year":"2017","journal-title":"Curr. Appl. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Stolerman, I.P. (2010). Flupenthixol. Encyclopedia of Psychopharmacology, Springer.","DOI":"10.1007\/978-3-540-68706-1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1592\/phco.29.1.64","article-title":"Antipsychotic-induced hyperprolactinemia","volume":"29","author":"Bostwick","year":"2009","journal-title":"Pharmacotherapy"},{"key":"ref_24","first-page":"1","article-title":"Flupenthixol versus low-potency first-generation antipsychotic drugs for schizophrenia","volume":"2014","author":"Tardy","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S0033-3182(71)71516-3","article-title":"Flupenthixol (fluanxol) in the treatment of psychosomatic disorders in medicine","volume":"12","year":"1971","journal-title":"Psychosomatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1192\/bjp.124.1.058","article-title":"Flupenthixol decanoate in schizophrenia","volume":"124","author":"Trueman","year":"1974","journal-title":"Br. J. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(13)60733-3","article-title":"Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple-treatments meta-analysis","volume":"382","author":"Leucht","year":"2013","journal-title":"Lancet"},{"key":"ref_28","unstructured":"Bradley, P.B., Flugel, F., and Hoch, P. (1964). 252 mit dem neuen Psykofarmakon Clopenthixol (Sordinol, Ciatyl) behandelte psychiatrische Patienten. Neuro-Psychopharmacology, Elsevier Publishing Co."},{"key":"ref_29","unstructured":"Gordon, M. (2017). Psychopharmacological Agents, Elsevier."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Schatzberg, A.F., and DeBattista, C. (2015). Manual of Clinical Psychopharmacology, American Psychiatric Publishing.","DOI":"10.1176\/appi.books.9781615370047"},{"key":"ref_31","first-page":"117","article-title":"Effects of dopaminergic agonist and antagonist drugs on cyclic 3\u2032,5\u2032 \u2013adenosine Monophosphate (cyclic AMP) production in rat brain homogenates","volume":"5","author":"Iversen","year":"1974","journal-title":"J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/BF00421933","article-title":"Pharmacology of neuroleptics upon repeated administration","volume":"34","author":"Fjalland","year":"1974","journal-title":"Psychopharmacologia"},{"key":"ref_33","unstructured":"Casey, D., and Christensen, A. (2012). Psychopharmacology: Current Trends: Current Trends, Springer Science & Business Media."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00335-013-9488-5","article-title":"The microbiome: Stress, health and disease","volume":"25","author":"Moloney","year":"2014","journal-title":"Mamm. Genome"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.euroneuro.2015.11.002","article-title":"Gut microbiota regulates key modulators of social behavior","volume":"26","author":"Parashar","year":"2016","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41564-018-0337-x","article-title":"The neuroactive potential of the human gut microbiota in quality of life and depression","volume":"4","author":"Falony","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.2174\/1568026619666181210151348","article-title":"Psychobiome Feeding Mind: Polyphenolics in Depression and Anxiety","volume":"18","author":"Matarazzo","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1007\/s12264-021-00730-8","article-title":"The Relationship Between the Gut Microbiome and Neurodegenerative Diseases","volume":"37","author":"Zhu","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1007\/s11427-016-5083-9","article-title":"Alzheimer\u2019s disease and gut microbiota","volume":"59","author":"Hu","year":"2016","journal-title":"Sci. China Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2016.11.018","article-title":"Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson\u2019s Disease","volume":"167","author":"Sampson","year":"2016","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105840","DOI":"10.1016\/j.phrs.2021.105840","article-title":"The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders","volume":"172","author":"Doboszewska","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_42","first-page":"1063","article-title":"Largactil in the treatment of tuberculosis","volume":"84","author":"Geiger","year":"1954","journal-title":"Schweiz. Med. Wochenschr."},{"key":"ref_43","first-page":"7","article-title":"The antimicrobial activity of non-antibiotics. Report from a congress on the antimicrobial effect of drugs other than antibiotics on bacteria, viruses, protozoa, and other organisms","volume":"100","author":"Kristiansen","year":"1992","journal-title":"Acta Pathol. Microbiol. Immunol. Scand. Suppl."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1699-0463.1993.tb00133.x","article-title":"Antimycobacterial activity of methdilazine (Md), an antimicrobic phenothiazine","volume":"101","author":"Chakrabarty","year":"1993","journal-title":"APMIS"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1179\/joc.2002.14.1.47","article-title":"Experimental studies on synergism between aminoglycosides and the antimicrobial antiinflammatory agent diclofenac sodium","volume":"14","author":"Annadurai","year":"2002","journal-title":"J. Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0255-0857(21)03067-X","article-title":"Evaluation of in vitro and in vivo antibacterial activity of dobutamine hydrochloride","volume":"21","author":"Sarkar","year":"2003","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_47","first-page":"285","article-title":"Amlodipine: A cardiovascular drug with powerful antimicrobial property","volume":"52","author":"Kumar","year":"2003","journal-title":"Acta Microbiol. Pol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1078\/0944-5013-00204","article-title":"Antimicrobial potentiality of a new non-antibiotic: The cardiovascular drug oxyfedrine hydrochloride","volume":"158","author":"Mazumdar","year":"2003","journal-title":"Microbiol. Res."},{"key":"ref_49","first-page":"192","article-title":"Antibacterial potential of an antispasmodic drug dicyclomine hydrochloride","volume":"118","author":"Karak","year":"2003","journal-title":"Indian J. Med. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3742\/OPEM.2006.6.2.126","article-title":"Assessment of antibacterial activity of the cardiovascular drug nifedipine","volume":"6","author":"Pal","year":"2006","journal-title":"Orient. Pharm. Exp. Med."},{"key":"ref_51","first-page":"847","article-title":"Studies on the antimicrobial potential of the cardiovascular drug lacidipine","volume":"21","author":"Dasgupta","year":"2007","journal-title":"In Vivo"},{"key":"ref_52","first-page":"355","article-title":"The antibacterial activity of the psychopharmacological agent clopenthixol and its two main metabolites","volume":"95","author":"Mortensen","year":"1987","journal-title":"Acta Pathol. Microbiol. Immunol. Scand. B"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ijantimicag.2005.08.014","article-title":"Antimicrobial potentiality of the thioxanthene flupenthixol through extensive in vitro and in vivo experiments","volume":"27","author":"Jeyaseeli","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.resmic.2012.10.007","article-title":"Thioridazine potentiates the effect of a beta-lactam antibiotic against Staphylococcus aureus independently of mecA expression","volume":"164","author":"Poulsen","year":"2013","journal-title":"Res. Microbiol."},{"key":"ref_55","first-page":"1","article-title":"Comparison of Antibacterial Activity of (\u2013) Thioridazine and Racemic Thioridazine in Staphylococcus aureus","volume":"1","author":"Poulsen","year":"2018","journal-title":"Am. J. Bioavailab. Bioequivalence"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1099\/jmm.0.071837-0","article-title":"Combination therapy with thioridazine and dicloxacillin combats meticillin-resistant Staphylococcus aureus infection in Caenorhabditis elegans","volume":"63","author":"Poulsen","year":"2014","journal-title":"J. Med. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s10096-011-1435-3","article-title":"Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol","volume":"31","author":"Jeyaseeli","year":"2012","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_58","first-page":"206","article-title":"A new vegetative stabilizer; 4560 RP","volume":"60","author":"Laborit","year":"1952","journal-title":"Presse Med."},{"key":"ref_59","first-page":"150","article-title":"3-Chloro-10-(3\u2032-dimethylaminopropyl)-phenothiazine hydrochloride in current neuro-psychiatry","volume":"54","author":"Sigwald","year":"1953","journal-title":"Bull. Mem. Soc. Med. Hop. Paris"},{"key":"ref_60","first-page":"514","article-title":"R\u00e9actions biologiques observ\u00e9es au cours du traitement par le chlorhydrate de dim\u00e9thyl-amino-propyl-N-chloroph\u00e9nothiazine (4560 R.P.)","volume":"50","author":"Delay","year":"1952","journal-title":"CR Congr\u00e9s M\u00e9dicine Ali\u00e9n Neurol."},{"key":"ref_61","first-page":"212","article-title":"Effects of chlorpromazine on bacteria and bacteriostatic complex in vitro","volume":"67","author":"Popper","year":"1959","journal-title":"Presse Med."},{"key":"ref_62","first-page":"876","article-title":"Contribution to the study of the antibiotic properties of chlorpromazine or 4560 RP","volume":"101","author":"Bourdon","year":"1961","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1159\/000239036","article-title":"Chlorpromazine: A drug potentially useful for treating mycobacterial infections","volume":"38","author":"Crowle","year":"1992","journal-title":"Chemotherapy"},{"key":"ref_64","first-page":"393","article-title":"The antibacterial effect of selected phenothiazines and thioxanthenes on slow-growing mycobacteria","volume":"94","author":"Kristiansen","year":"1986","journal-title":"Acta Pathol. Microbiol. Immunol. Scand. B"},{"key":"ref_65","first-page":"521","article-title":"Studies on antituberculotic action of some phenothiazine derivatives in vitro","volume":"239","year":"1977","journal-title":"Zent. Bakteriol. Orig. A"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1128\/AAC.47.3.917-922.2003","article-title":"Clinical concentrations of thioridazine kill intracellular multidrug-resistant Mycobacterium tuberculosis","volume":"47","author":"Ordway","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1093\/jac\/38.6.1049","article-title":"Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: Potential use for initial therapy of freshly diagnosed tuberculosis","volume":"38","author":"Amaral","year":"1996","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1574-6968.1993.tb06337.x","article-title":"Trifluoperazine inhibits the incorporation of labelled precursors into lipids, proteins and DNA of Mycobacterium tuberculosis H37Rv","volume":"110","author":"Ratnakar","year":"1993","journal-title":"Fems Microbiol. Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/j.ijantimicag.2013.01.001","article-title":"Activity of the efflux pump inhibitor SILA 421 against drug-resistant tuberculosis","volume":"41","author":"Simons","year":"2013","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ijantimicag.2009.02.015","article-title":"In vitro activity of thioridazine against mycobacteria","volume":"34","author":"Amaral","year":"2009","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_71","first-page":"1","article-title":"Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present","volume":"18","author":"Kristiansen","year":"2015","journal-title":"Int. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1135\/cccc19750719","article-title":"2- And 3-fluoro derivatives of clorotepin and related compounds; 6- And 7-fluoro derivative of chlorprothixene","volume":"40","author":"Protiva","year":"1975","journal-title":"Collect. Czechoslov. Chem. Commun."},{"key":"ref_73","first-page":"437","article-title":"Stereo-isomeric dissociation of the antibacterial and the neuroleptic effect of clopenthixol","volume":"89","author":"Kristiansen","year":"1981","journal-title":"Acta Pathol. Microbiol. Scand. B"},{"key":"ref_74","unstructured":"Smith, D.F. (1984). Antipsychotic Drugs: Configurational Stereoisomers. Handbook of Stereoisomers: Drugs in Psychopharmacology, CRC Press Inc."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1600-0773.1991.tb01260.x","article-title":"Effect of Selected Neuroleptic Agents and Stereo-Isomeric Analogues on Virus and Eukaryotic Cells","volume":"69","author":"Kristiansen","year":"1991","journal-title":"Pharmacol. Toxicol."},{"key":"ref_76","first-page":"77","article-title":"Involvement of calmodulin in granulocyte chemotaxis: The effect of calmodulin inhibitors","volume":"38","author":"Elferink","year":"1982","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/0006-291X(81)91631-4","article-title":"Inhibition of the neutrophil oxidative burst and degranulation by phenothiazines","volume":"102","author":"Ochs","year":"1981","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_78","first-page":"677","article-title":"Effects of trifluoperazine on human neutrophil function","volume":"44","author":"Smith","year":"1981","journal-title":"Immunology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/0006-2952(79)90287-9","article-title":"Chlorpromazine inhibits phagocytosis and exocytosis in rabbit polymorphonuclear leukocytes","volume":"28","author":"Elferink","year":"1979","journal-title":"Biochem. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/0006-2952(81)90223-9","article-title":"Decreased viscosity of human erythrocyte suspension induced by chlorpromazine and isoxsuprine","volume":"30","author":"Suda","year":"1981","journal-title":"Biochem. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0005-2736(81)90422-3","article-title":"Fluidity of human erythrocyte membrane and effect of chlorpromazine on fluidity and phase separation of membrane","volume":"649","author":"Ogiso","year":"1981","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_82","first-page":"199","article-title":"In vitro modulation of human neutrophil chemotaxis by cis(Z)- and trans(E)-clopenthixol, and chlorpromazine","volume":"93","author":"Rechnitzer","year":"1985","journal-title":"Acta Pathol. Microbiol. Immunol. Scand. C"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"20865","DOI":"10.1039\/C4RA16551A","article-title":"Molar ratios of therapeutic water-soluble phenothiazine\u00b7water-insoluble phospholipid adducts reveal a Fibonacci correlation and a putative link for structure\u2013activity relationships","volume":"5","author":"Keyzer","year":"2015","journal-title":"RSC Adv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.4049\/jimmunol.124.4.1963","article-title":"Lipid requirements for leukocyte chemotaxis and phagocytosis: Effects of inhibitors of phospholipid and cholesterol synthesis","volume":"124","author":"Pike","year":"1980","journal-title":"J. Immunol."},{"key":"ref_85","unstructured":"Usdin, E., Forrest, I. (1977). The Thioxanthenes. Psychotherapeutic Drugs, Part II, Marcel Dekker Inc."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/j.1600-0773.1982.tb00976.x","article-title":"A study on inhibition of cholera toxin-induced intestinal hypersecretion by neuroleptics","volume":"50","author":"Larsen","year":"1982","journal-title":"Acta Pharmacol. Toxicol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1600-0773.1992.tb00576.x","article-title":"The antibacterial effect of some neuroleptics on strains isolated from patients with meningitis","volume":"71","author":"Mortensen","year":"1992","journal-title":"Pharmacol. Toxicol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0924-8579(99)00157-0","article-title":"Inhibition of HIV replication by neuroleptic agents and their potential use in HIV infected patients with AIDS related dementia","volume":"14","author":"Kristiansen","year":"2000","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7448","DOI":"10.1073\/pnas.85.20.7448","article-title":"Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates","volume":"85","author":"Sarin","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","first-page":"149","article-title":"The Fight Against Malaria: An Industrial Necessity for Our African Colonies","volume":"2","author":"Ross","year":"1903","journal-title":"J. R. Afr. Soc."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0035-9203(84)90122-6","article-title":"Concomitant resistance to pyrimethamine and cycloguanil of chloroquine-resistant falciparum malaria from East Africa: An in vitro study of 12 isolates","volume":"78","author":"Schapira","year":"1984","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1080\/00034983.1983.11811723","article-title":"RII-RIII chloroquine resistant Plasmodium falciparum malaria from East Africa: Studies of the in vivo and in vitro response to chloroquine","volume":"77","author":"Jepsen","year":"1983","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_93","first-page":"953","article-title":"\u00dcber die wirkung des MethylenBlau bei Malaria","volume":"28","author":"Guttmann","year":"1891","journal-title":"Berl. Klin. Wochenschr."},{"key":"ref_94","first-page":"249","article-title":"The susceptibility of Plasmodium falciparum in vitro to chlorpromazine and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol","volume":"93","author":"Kristiansen","year":"1985","journal-title":"Acta Pathol. Microbiol. Immunol. Scand. B"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1128\/AAC.16.6.710","article-title":"Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique","volume":"16","author":"Desjardins","year":"1979","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_96","first-page":"235","article-title":"Inhibition of bacterial plasmid replication by stereoselective binding by tricyclic psychopharmacons","volume":"43","author":"Nakamura","year":"1984","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2174\/1568026013395605","article-title":"Multidrug efflux in Pseudomonas aeruginosa: Components, mechanisms and clinical significance","volume":"1","author":"Poole","year":"2001","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0006-2952(00)00291-4","article-title":"Antibiotic efflux pumps","volume":"60","author":"Balzi","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/S0140-6736(00)04403-2","article-title":"Whole genome sequencing of meticillin-resistant Staphylococcus aureus","volume":"357","author":"Kuroda","year":"2001","journal-title":"Lancet"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1128\/AAC.43.10.2404","article-title":"Multiple novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus","volume":"43","author":"Markham","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"6630","DOI":"10.1021\/bi983038l","article-title":"A single amino acid residue contributes to distinct mechanisms of inhibition of the human multidrug transporter by stereoisomers of the dopamine receptor antagonist flupentixol","volume":"38","author":"Dey","year":"1999","journal-title":"Biochemistry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1699-0463.1988.tb00984.x","article-title":"Synergy between a non-neuroleptic thioxanthene stereo-isomer and penicillin in vivo","volume":"96","author":"Kristiansen","year":"1988","journal-title":"APMIS"},{"key":"ref_103","first-page":"105","article-title":"Structural features determining activity of phenothiazines and related drugs for inhibition of cell growth and reversal of multidrug resistance","volume":"35","author":"Ford","year":"1989","journal-title":"Mol. Pharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/0006-2952(90)90210-C","article-title":"Tricyclic drugs reduce proton motive force in Leishmania donovani promastigotes","volume":"39","author":"Zilberstein","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1128\/AAC.47.2.719-726.2003","article-title":"Phenothiazines and thioxanthenes inhibit multidrug efflux pump activity in Staphylococcus aureus","volume":"47","author":"Kaatz","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_106","first-page":"418","article-title":"The Accepted \u201cClinical Interaction Model\u201d: A Special Case of Reality","volume":"9","author":"Kristiansen","year":"2017","journal-title":"J. Bioequiv. Availab."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Nehme, H., Saulnier, P., Ramadan, A.A., Cassisa, V., Guillet, C., Eveillard, M., and Umerska, A. (2018). Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0189950"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"31","DOI":"10.18433\/J3BG65","article-title":"Multidrug resistance reversal effects of aminated thioxanthones and interaction with cytochrome P450 3A4","volume":"15","author":"Palmeira","year":"2012","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Torregrosa-Chinillach, A., and Chinchilla, R. (2021). Synthesis of xanthones, thioxanthones and Acridones by a metal-free photocatalytic oxidation using visible light and molecular oxygen. Molecules, 26.","DOI":"10.3390\/molecules26040974"},{"key":"ref_110","first-page":"1","article-title":"Density functional theory study of structural and electronic properties of trans and cis structures of thiothixene as a nano-drug","volume":"23","author":"Balali","year":"2017","journal-title":"J. Mol. Model."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Wrzesinski, K., Aln\u00f8e, S., Jochumsen, H.H., Mikkelsen, K., Bryld, T.D., Vistisen, J.S., Aln\u00f8e, P.W., and Fey, S.J. (2021). A Purpose-Built System for Culturing Cells as In Vivo Mimetic 3D Structures. BioMechanics and Functional Tissue Engineering [Working Title], IntechOpen.","DOI":"10.5772\/intechopen.96091"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.celrep.2016.04.074","article-title":"Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis","volume":"15","author":"Mattei","year":"2016","journal-title":"Cell Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.addr.2017.12.013","article-title":"Engineered cell and tissue models of pulmonary fibrosis","volume":"129","author":"Sundarakrishnan","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1016\/j.celrep.2019.01.108","article-title":"Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions","volume":"26","author":"Co","year":"2019","journal-title":"Cell Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e01404","DOI":"10.1128\/AAC.01404-19","article-title":"Clostridioides difficile-associated antibiotics alter human mucosal barrier functions by microbiome-independent mechanisms","volume":"64","author":"Kester","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Jensen, A.S. (2014). Cardiac Action Potential Prolongation Induced by Isolated Thioridazine Enantiomers, Aalborg University.","DOI":"10.13052\/rp-9788793237421"},{"key":"ref_117","first-page":"7","article-title":"Differential effects of thioridazine enantiomers on action potential duration in rabbit papillary muscle","volume":"747C","author":"Jensen","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1055\/s-0039-1690834","article-title":"Synthesis of the Enantiomers of Thioridazine","volume":"4","author":"Antonsen","year":"2020","journal-title":"SynOpen"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/1\/196\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:55:38Z","timestamp":1760169338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/1\/196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,29]]},"references-count":118,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["molecules27010196"],"URL":"https:\/\/doi.org\/10.3390\/molecules27010196","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,29]]}}}