title: Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present.
abstract: Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-antibiotics evolved in this background. From the antimalarial and antitrypanosomial dye methylene blue, chemically similar compounds, the phenothiazines, were developed. The phenothiazines were first recognised for their antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-antibiotics. The emergence of highly drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several phenothiazines awakened the interest among scientists to determine their antimycobacterial activity. Chlorpromazine, trifluoperazine, methdilazine and thioridazine were found to have distinct antitubercular action. Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (-) thioridazine is a more active antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down thioridazine and its (-) form to be combined with other antitubercular drugs to treat infections by drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease.
authors.affiliation: Memphys Centre for Biomembrane Physics, Department of Physics and Chemistry, University of Southern Denmark, Odense, Denmark.
authors.forename: Jette E
authors.initials: JE
authors.lastname: Kristiansen
authors.affiliation: Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Saraldighi (E), Boral, Kolkata, India.
authors.forename: Sujata G
authors.initials: SG
authors.lastname: Dastidar
authors.affiliation: Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Saraldighi (E), Boral, Kolkata, India.
authors.forename: Shauroseni
authors.initials: S
authors.lastname: Palchoudhuri
authors.affiliation: Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Saraldighi (E), Boral, Kolkata, India.
authors.forename: Debalina Sinha
authors.initials: DS
authors.lastname: Roy
authors.affiliation: Department of Physics, Jadavpur University, Kolkata, India.
authors.forename: Sukhen
authors.initials: S
authors.lastname: Das
authors.affiliation: King Christian X Hospital for Rheumatic Diseases, University of Southern Denmark, Grasten, Denmark.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hendricks
authors.affiliation: Department of Chemistry, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jørn B
authors.initials: JB
authors.lastname: Christensen
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002746:Chlorpromazine / Q000627:therapeutic use; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D010640:Phenothiazines / Q000627:therapeutic use*; D013881:Thioridazine / Q000627:therapeutic use; D014268:Trifluoperazine / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D000995:Antitubercular Agents; D010640:Phenothiazines; D014268:Trifluoperazine; C044642:methdilazine; D013881:Thioridazine; D002746:Chlorpromazine
keywords: Mycobacterium tuberculosis; phenotiazines; thioridazine; tuberculosis