Kristiansen Jette E, Dastidar Sujata G, Palchoudhuri Shauroseni, Roy Debalina Sinha, Das Sukhen, Hendricks Oliver, Christensen Jørn B
Memphys Centre for Biomembrane Physics, Department of Physics and Chemistry, University of Southern Denmark, Odense, Denmark.
Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, Saraldighi (E), Boral, Kolkata, India.
Int Microbiol. 2015 Mar;18(1):1-12. doi: 10.2436/20.1501.01.229.
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.
从历史上看，合成化合物具有多种作用是普遍现象而非个别情况。非抗生素科学就是在这样的背景下发展起来的。从抗疟疾和抗锥虫的染料亚甲蓝出发，开发出了化学结构相似的化合物——吩噻嗪类。吩噻嗪类最初因其抗精神病特性而被认可，但不久后其抗菌功能也为人所知，随后这类化合物被归类为非抗生素。高度耐药细菌的出现引发了对新型平价化合物的迫切需求。几种吩噻嗪类引起了科学家们的兴趣，促使他们去测定其抗分枝杆菌活性。氯丙嗪、三氟拉嗪、甲硫达嗪和硫利达嗪被发现具有明显的抗结核作用。硫利达嗪处于领先地位，因为研究人员多次宣称其具有潜力。尽管硫利达嗪以其对中枢神经系统和心脏的毒性副作用而闻名，但多个研究小组广泛且反复进行的体外和体内研究表明，只需极少量的硫利达嗪就能杀死肺部巨噬细胞内的结核杆菌，而结核杆菌正是试图在肺部悄悄存活和繁殖的。如此小的剂量不会产生副作用。最近的研究表明，（-）硫利达嗪是一种更具活性的抗菌剂，且没有通常会出现的毒副作用。这篇综述描述了将硫利达嗪及其（-）形式与其他抗结核药物联合使用以治疗耐多药结核分枝杆菌感染并试图根除这种致命疾病的可能性。
