Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present Authors Jette E. Kristiansen Memphys Centre for Biomembrane Physics, Department of Physics and Chemistry, University of Southern Denmark, Odense. Sujata G. Dastidar Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Saraldighi (E), Boral, Kolkata. Shauroseni Palchoudhuri Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Saraldighi (E), Boral, Kolkata. Debalina Sinha Roy Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Saraldighi (E), Boral, Kolkata. Sukhen Das Department of Physics, Jadavpur University, Kolkata. Oliver Hendricks King Christian X Hospital for Rheumatic Diseases, University of Southern Denmark, Grasten. Jørn B. Christensen Department of Chemistry, University of Copenhagen, Copenhagen. Keywords: Mycobacterium tuberculosis, phenotiazines, thioridazine, tuberculosis 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. [Int Microbiol 2015; 18(1):1-12]Keywords: Mycobacterium tuberculosis · phenotiazines · thioridazine · tuberculosis Downloads PDF Issue Vol. 18 No. 1 (2015) Section Research Reviews License Submission of a manuscript to International Microbiology implies: that the work described has not been published before, including publication in the World Wide Web (except in the form of an Abstract or as part of a published lecture, review, or thesis); that it is not under consideration for publication elsewhere; that all the coauthors have agreed to its publication. The corresponding author signs for and accepts responsability for releasing this material and will act on behalf of any and all coauthors regarding the editorial review and publication process.If an article is accepted for publication in International Microbiology, the authors (or other copyright holder) must transfer to the journal the right–not exclusive–to reproduce and distribute the article including reprints, translations, photographic reproductions, microform, electronic form (offline, online) or any other reproductions of similar nature. Nevertheless, all article in International Microbiology will be available on the Internet to any reader at no cost. The journal allows users to freely download, copy, print, distribute, search, and link to the full text of any article, provided the authorship and source of the published article is cited. The copyright owner's consent does not include copying for new works, or resale. In these cases, the specific written permission of International Microbiology must first be obtained.Authors are requested to create a link to the published article on the journal's website. The link must be accompanied by the following text: "The original publication is available on LINK at <http://www.im.microbios.org>. Please use the appropiate URL for the article in LINK. Articles disseminated via LINK are indexed, abstracted, and referenced by many abstracting and information services, bibliographic networks, subscription agencies, library networks, and consortia.
