{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T05:23:35Z","timestamp":1704864215803},"reference-count":12,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,12,23]],"date-time":"2010-12-23T00:00:00Z","timestamp":1293062400000},"content-version":"vor","delay-in-days":3796,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotech and App Biochem"],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:p>It has been shown previously that tricyclic neuroleptics like clomipramine and chlorpromazine have lethal effects on <jats:italic>Leishmania donovani<\/jats:italic> and <jats:italic>L. major<\/jats:italic>, and other studies indicate that the phenothiazine inhibitors of trypanothione reductase are potential anti\u2010trypanosomal and anti\u2010leishmanial drugs. With this in mind and our original observation on the presence of trypanothione in <jats:italic>Entamoeba histolytica<\/jats:italic> HK9, we examined the possible inhibitory effects of various phenothiazine and tricyclic derivatives on this human parasite. We found that drugs like clomipramine (KD002), the most potent <jats:italic>in vitro<\/jats:italic> inhibitor of trypanothione reductase among 30 tricyclic compounds tested, at 25 \u03bcM after 24 h of culture under aerobic conditions, caused a substantial decrease in the number of <jats:italic>E. histolytica<\/jats:italic> HK9 trophozoites, from approx. 15\u00d710<jats:sup>6<\/jats:sup> to 5\u00b737\u00d710<jats:sup>6<\/jats:sup> cells, and at 100 \u03bcM to 0\u00b78\u00d710<jats:sup>6<\/jats:sup> cells. A substantial inhibitory effect on cell proliferation could also be demonstrated with metronidazol (used clinically against amoebiasis). Under similar experimental conditions other tricyclic and phenothiazine derivatives (OFKs), designed originally to inhibit the trypanothione reductase of trypanosomatides, had an inhibitory effect of 16 to 95%. For comparison, similar results were obtained using clomipramine and a phenothiazine derivative (OFK006) with <jats:italic>Trypanosoma cruzi<\/jats:italic> and <jats:italic>Crithidia luciliae<\/jats:italic>, except that with the latter the inhibitory effect of clomipramine was less dramatic. Experiments comparing two <jats:italic>E. histolytica<\/jats:italic> strains showed that normal cell proliferation under anaerobiosis was higher in strain HK9 than in HM1, which is highly virulent, but that metronidazol and clomipramine were less effective against HM1. Two other drugs tested, diphenydramine (KD005) and a phenothiazine derivative (OFK008), also had significant but lower inhibitory effects on both strains. The inhibitory activity on cell proliferation and the lytic effects on this human parasite by the tricyclic compounds clomipramine, chlorpromazine and others, as well as by the phenothiazine derivatives, indicate that they can be considered potential anti\u2010amoebic agents.<\/jats:p>","DOI":"10.1042\/ba19990099","type":"journal-article","created":{"date-parts":[[2003,11,26]],"date-time":"2003-11-26T16:18:11Z","timestamp":1069863491000},"page":"61-67","source":"Crossref","is-referenced-by-count":11,"title":["Inhibitory and lytic effects of phenothiazine derivatives and related tricyclic neuroleptic compounds, on <i>Entamoeba histolytica<\/i> HK9 and HM1 trophozoites"],"prefix":"10.1002","volume":"32","author":[{"given":"Ra\u00fal N.","family":"Ondarza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ang\u00e9lica","family":"Iturbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Hurtado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,12,23]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm960814j"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6124040"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.25.5.571"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6505677"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(89)90102-1"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6322306"},{"key":"e_1_2_5_8_2","first-page":"S73","volume":"28","author":"Ondarza R.N.","year":"1997","journal-title":"Arch. 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