{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T02:24:57Z","timestamp":1784946297897,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T00:00:00Z","timestamp":1398124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Thiourea derivatives display a broad spectrum of applications in chemistry, various industries, medicines and various other fields. Recently, different thiourea derivatives have been synthesized and explored for their anti-microbial properties.  In this study, four carbonyl thiourea derivatives were synthesized and characterized,  and then further tested for their anti-amoebic properties on two potential pathogenic species of Acanthamoeba, namely A. castellanii (CCAP 1501\/2A) and A. polyphaga (CCAP 1501\/3A). The results indicate that these newly-synthesized thiourea derivatives are active against both Acanthamoeba species. The IC50 values obtained were in the range  of 2.39\u20138.77 \u00b5g\u00b7mL\u20111 (9.47\u201330.46 \u00b5M) for A. castellanii and 3.74\u20139.30 \u00b5g\u00b7mL\u20111 (14.84\u201331.91 \u00b5M) for A. polyphaga. Observations on the amoeba morphology indicated that the compounds caused the reduction of the amoeba size, shortening of their acanthopodia structures, and gave no distinct vacuolar and nuclear structures in the amoeba cells. Meanwhile, fluorescence microscopic observation using acridine orange and propidium iodide (AOPI) staining revealed that the synthesized compounds induced compromised-membrane in the amoeba cells. The results of this study proved that these new carbonyl thiourea derivatives, especially compounds M1 and M2 provide potent cytotoxic properties toward pathogenic Acanthamoeba to suggest that they can be developed as new anti-amoebic agents for the treatment of Acanthamoeba keratitis.<\/jats:p>","DOI":"10.3390\/molecules19045191","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T12:18:37Z","timestamp":1398169117000},"page":"5191-5204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Anti-Amoebic Properties of Carbonyl Thiourea Derivatives"],"prefix":"10.3390","volume":"19","author":[{"given":"Maizatul","family":"Ibrahim","sequence":"first","affiliation":[{"name":"School of Fundamental Science, Universiti Malaysia Terengganu, Kuala Terengganu, Terengganu 21030, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd","family":"Mohd Yusof","sequence":"additional","affiliation":[{"name":"School of Fundamental Science, Universiti Malaysia Terengganu, Kuala Terengganu, Terengganu 21030, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nakisah","family":"Amin","sequence":"additional","affiliation":[{"name":"School of Fundamental Science, Universiti Malaysia Terengganu, Kuala Terengganu, Terengganu 21030, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S385","DOI":"10.1093\/clind\/13.Supplement_5.S385","article-title":"Ecology of Acanthamoeba","volume":"13","year":"1991","journal-title":"Rev. Infect. Dis."},{"key":"ref_2","unstructured":"Page, F.C. (1988). Freshwater Biological Association, Culture Collection of Algae and Protozoa."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/00003226-200203000-00016","article-title":"Development and application of an in vitro susceptibility test for Acanthamoeba species isolated from keratitis to polyhexamethylene biguanide and chlorhexidine","volume":"21","author":"Narasimhan","year":"2002","journal-title":"Cornea"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1128\/CMR.16.2.273-307.2003","article-title":"Acanthamoeba spp. as agents of disease in humans","volume":"16","author":"Cabral","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0140-6736(95)90670-3","article-title":"Chemotherapy for Acanthamoeba keratitis","volume":"345","author":"Elder","year":"1995","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0161-6420(92)31994-3","article-title":"Treatment of Acanthamoeba keratitis with polyhexamethylene biguanide","volume":"99","author":"Larkin","year":"1992","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/sj.eye.6700563","article-title":"Acanthamoeba keratitis update\u2014Incidence, molecular epidemiology and new drugs for treatment","volume":"17","author":"Seal","year":"2003","journal-title":"Eye"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1442-9071.1998.tb01317.x","article-title":"Acanthamoebakeratitis in New Zealand, including two cases with in vivo resistance to polyhexamethylene biguanide","volume":"26","author":"Murdoch","year":"1998","journal-title":"Aust. New Zeal. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/jac\/46.1.27","article-title":"Emergence of resistance to biocides during differentiation of Acanthamoeba castellanii","volume":"46","author":"Turner","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/eye.1990.132","article-title":"Acanthamoeba keratitis: Resistance to medical therapy","volume":"4","author":"Ficker","year":"1990","journal-title":"Eye"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1016\/j.ejmech.2007.12.007","article-title":"Synthesis and anti-amoebic activity of metronidazole thiosemicarbazone analogues","volume":"43","author":"Abid","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/j.ejmech.2007.10.026","article-title":"Syntheses and evaluation of 3-(3-bromophenyl)-5-phenyl-1-(thiazolo[4,5-b]quinoxaline-2-yl)-2pyrazoline derivatives","volume":"43","author":"Budakoti","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/(SICI)1098-2280(1998)31:4<362::AID-EM9>3.0.CO;2-K","article-title":"S-Oxygenation of thiourea results in the formation of genotoxic products","volume":"31","author":"Nill","year":"1998","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1016\/j.ejmech.2007.12.012","article-title":"Synthesis, characterization and in vitro antibacterial activity of thiourea and urea derivatives of steroids","volume":"43","author":"Khan","year":"2008","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.carres.2007.11.024","article-title":"Synthesis of acyl thiourea derivatives of chitosan and their anti-microbial activities in vitro","volume":"343","author":"Zhong","year":"2008","journal-title":"Carbohydr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijbiomac.2005.12.009","article-title":"Antifungal efficacy of chitosan and its thiourea derivatives upon the growth of some sugar-beet pathogens","volume":"38","author":"Eweis","year":"2006","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.carbpol.2004.11.020","article-title":"Preparation of high anti-microbial activity chitosan-Ag+ complex","volume":"60","author":"Chen","year":"2005","journal-title":"Carbohydr. Polym."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0014-827X(02)01250-8","article-title":"Synthesis and anti-microbial activity of some pyridinyliminothiazoline derivatives","volume":"57","year":"2002","journal-title":"Il Farmaco"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"53123","DOI":"10.1074\/jbc.M311209200","article-title":"Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis","volume":"278","author":"Phetsuksiri","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/0273-2300(88)90009-8","article-title":"Goitrogens and thyroid follicular cell neoplasia. Evidence for a threshold process","volume":"8","author":"Paynter","year":"1988","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_21","first-page":"o828","article-title":"3-(3-Benzoylthioureido) propionic acid","volume":"E59","author":"Yusof","year":"2003","journal-title":"Acta Crystallogr."},{"key":"ref_22","first-page":"o1536","article-title":"1-(4-Chlorobutanoyl)-3-(2-chloro phenyl)thiourea","volume":"E68","author":"Yusof","year":"2012","journal-title":"Acta Crystallogr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0378-8741(01)00270-7","article-title":"A search for natural bioactive compounds in Bolivia through a multi disciplinary sciences approach. Part V. Evaluation of the antimalarial activity of plants used by the Tacana Indians","volume":"77","author":"Deharo","year":"2001","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1128\/JCM.43.2.629-634.2005","article-title":"Development of colorimetric microtiter plate assay for assessment of anti-microbials against Acanthamoeba","volume":"43","author":"McBride","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Patnaik, P. (2007). A Comprehensive Guide to the Hazardous Properties of Chemical Substances, Wiley-Interscience.","DOI":"10.1002\/9780470134955"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6475","DOI":"10.1016\/S0040-4020(01)00539-7","article-title":"Novel strategy for the synthesis of fluorinated \u03b2-amino acid derivatives from \u03942-oxazolines","volume":"57","author":"Fustero","year":"2001","journal-title":"Tetrahedron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0039-128X(93)90015-F","article-title":"Synthesis of new amino acid and peptide derivatives of estradiol and their binding affinities for the estrogen receptor","volume":"58","author":"Ye","year":"1993","journal-title":"Steroids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jsps.2010.05.002","article-title":"Synthesis and anti-microbial activity of new 4-thiazolidinone derivatives containing 2-amino-6-methoxybenzothiazole","volume":"18","author":"Patel","year":"2010","journal-title":"Saudi Pharm. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1083\/jcb.39.1.95","article-title":"The fine structure of Acanthamoeba castellanii, kinetics and morphology. I. The Trophozoite","volume":"39","author":"Bowers","year":"1968","journal-title":"J. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s002840010325","article-title":"Pathogenicity, morphology, and differentiation of Acanthamoeba","volume":"43","author":"Khan","year":"2001","journal-title":"Curr. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1083\/jcb.62.2.533","article-title":"Localization of lipophosphonoglycan on both sides of Acanthamoeba plasma membrane","volume":"62","author":"Bowers","year":"1974","journal-title":"J. Cell Biol."},{"key":"ref_32","unstructured":"Khan, N.A. (2008). Emerging Protozoan Pathogens, Taylor & Francis Group."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev.mi.30.100176.001201","article-title":"Differentiation in Acanthamoeba castellanii","volume":"30","author":"Weisman","year":"1976","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_34","unstructured":"Coder, D.M. (1997). Current Protocols in Cytometry, Wiley. [2nd ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-0320(19970101)27:1<1::AID-CYTO2>3.0.CO;2-L","article-title":"Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death (necrosis)","volume":"27","author":"Darzynkiewicz","year":"1997","journal-title":"Cytometry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1089\/154065804322966315","article-title":"Use of multiple assay endpoints to investigate the effects of incubation time, dose of toxin, and plating density in cell-based cytotoxicity assays","volume":"2","author":"Riss","year":"2004","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0091-679X(08)60989-9","article-title":"Fluorescence labeling and microscopy of DNA","volume":"30","author":"Jovin","year":"1989","journal-title":"Methods Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hannun, Y.A., and Boustany, R.M. (1999). Apoptosis in Neurobiology, CRC Press.","DOI":"10.1201\/9780367801946"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1128\/AAC.39.2.339","article-title":"Amoebicidal efficiencies of various diamidines against two strains of Acanthamoeba polyphaga","volume":"39","author":"Perrine","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s11274-011-0927-8","article-title":"Anti-amoebic properties of a Malaysian marine sponge Aaptos sp. on Acanthamoeba castellanii","volume":"28","author":"Nakisah","year":"2012","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/0020-7519(94)90162-7","article-title":"In vitro assessment of susceptibility of Acanthamoeba polyphaga to drugs using combined methods of dye-binding assay and uptake of radiolabeled adenosine","volume":"24","author":"Asiri","year":"1994","journal-title":"Int. J. Parasitol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1128\/AAC.32.11.1725","article-title":"Use of microdilution to assess in vitro anti-amoebic activities of Bruceajavanica fruits, Simaroubaamara Stem, and a number of Quassinoids","volume":"32","author":"Wright","year":"1988","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1046\/j.1537-2995.2000.40060693.x","article-title":"HPC viability measurement: Trypan blue versus acridine orange and propidium iodide","volume":"40","author":"Mascotti","year":"2000","journal-title":"Transfusion"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/4\/5191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:10:34Z","timestamp":1760217034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/19\/4\/5191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,22]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2014,4]]}},"alternative-id":["molecules19045191"],"URL":"https:\/\/doi.org\/10.3390\/molecules19045191","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,22]]}}}