ANTI-AMOEBIC ACTIVITIES OF SYNTHETIC AMINOTHIOUREA DERIVATIVES AGAINST Acanthamoeba castellanii
NAKISAH, M.A.1,3*, MOHD SUKERI, M.Y.2 and NORHANIMAH, F.1
1Department of Biological Sciences, 2Department of Chemical Sciences, Faculty of Science and Technology, 3Institute of Oceanography, Universiti Malaysia Terengganu, 21030, Kuala Terengganu, Terengganu, Malaysia. *E-mail:
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ABSTRACT
This study was carried out to observe the cytotoxicity and genotoxicity properties of three novel compounds of synthetic aminothiourea derivatives on a pathogenic Acanthamoeba castellanii (IMR isolate) in order to search for a new anti- acanthamoeba agent especially for treatment of Acanthamoeba keratitis. In cytotoxicity study, viability of cells and CD50 of the compounds on A. castellanii were determined using eosin dye assay. The amoebae were treated with three aminothiourea derivatives compounds at different concentrations at 30°C for 72h. The compounds used were N- (benzyl(carboxy)carbamothioyl)-2-methylbenzamide, 3-(1–carbamoyl–3-(4–chlorobenzoyl)thioureido)propanoic acid, and 2- [3-(Furan-2-carbonylthioureido]acetic acid that were labeled in this study as C1, C2 and C3, respectively to facilitate discussion. Genotoxicity effect of the synthetic aminothiourea derivatives on A. castellanii was performed at compound concentrations of CD10, CD25 and CD50 using the Comet assay. The CD50 values of C1, C2 and C3 compounds obtained in this study were 45.0 µg/mL, 62.5 µg/mL and 45.0 µg/mL, respectively. The DNA damage observed in A. castellanii cells after treated with C1, C2 and C3 compounds varied depending on the compounds and their concentrations used. In general, DNA damage observed in individual cells of A. castellanii by the C2 compound treatment was more severe than the treatment with C1 and C3. Due to higher CD50 value in C2 compared to C1 and C3 based on the DNA damage imposed on the amoeba, C2 compound which is the 3-(1–carbamoyl–3-(4–chlorobenzoyl)thioureido)propanoic acid is considered the most potent compound with anti-Acanthamoeba activities observed in the present study.
ABSTRAK
Kajian ini dilakukan untuk melihat sifat-sifat kesitotoksikan dan kegenotoksikan tiga sebatian terbitan aminotiourea ke atas patogen Acanthamoeba castellanii (isolat IMR). Dalam kajian kesitotoksikan, daya hidup sel ameba dan CD50 sebatian tersebut ditentukan dengan menggunakan cerakin pewarna eosin. Ameba dirawat dengan tiga sebatian terbitan aminotiourea pada kepekatan yang berbeza selama 72 jam pada 30°C. Sebatian yang digunakan adalah asid N-(benzal(karboksi)karbamotiol-2- metilbenzamida, asid propanoik 3-(1-karboksi-3-(4-klorobenzoil)tioureido) dan asid asetik 2-(3-furan-2-karboniltioreido) yang dilabel sebagai C1, C2 and C3, masing-masing bagi memudahkan perbincangan. Kesan kegenotoksikan sebatian-sebatian terbitan ini ke atas Acanthamoeba dilakukan pada kepekatan CD10, CD25 dan CD50 dengan menggunakan cerakin Comet. Nilai CD50 yang diperolehi untuk C1, C2 and C3 adalah 45.0 µg/mL, 62.5 µg/mL dan 45.0 µg/mL, masing-masing. Tahap kerosakan DNA pada sel Acanthamoeba adalah berlainan bergantung kepada sebatian dan juga kepekatan yang digunakan. Secara umumnya, tahap kerosakan DNA pada sel yang dirawat dengan C2 lebih teruk dibandingkan dengan sel yang dirawat dengan C1 dan C3. Walaupun nilai CD50 C2 lebih tinggi daripada C1 dan C3, berdasarkan kerosakan DNA ameba, sebatian C2 iaitu asid propanoik 3-(1-karboksi-3-(4-klorobenzoil)tioureido) dianggap sebatian yang paling kuat mempunyai aktiviti anti-Acanthamoeba dalam kajian ini.
Key words: Aminothiourea derivatives, Acanthamoeba, genotoxicity, cytotoxicity, CD50
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