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العنوان
Identification of Cytotoxicity of Novel Trisubstituted Thiazoles Antimicrobial Compounds /
المؤلف
Mohammed, Mohammed Abdelhadi.
هيئة الاعداد
باحث / محمد عبد الهادى محمد
مشرف / عادل شحاته محمود
مناقش / على حسين عبد الرحمن
مناقش / أحمد عبد الباقى الشرقاوى
الموضوع
Veterinary Toxicology.
تاريخ النشر
2016.
عدد الصفحات
80 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Veterinary (miscellaneous)
الناشر
تاريخ الإجازة
29/9/2016
مكان الإجازة
جامعة أسيوط - كلية الطب البيطري - Forensic Medicine and Toxicology
الفهرس
Only 14 pages are availabe for public view

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Abstract

In the present study we investigated the potential toxicity of five thiazole antimicrobial compounds (1A, 19A,R1, 11M and 12M) on murine macrophage cell line (J774A.1) (ATCC® TIB-67™) obtained from American Type Culture Collection (ATCC). The used cytotoxicity and cell proliferation assays were, 1) assays based on metabolic activity such as a) Cell Proliferation assay and b) ATP content assay, 2) Plasma membrane integrity assay, and 3) assays based on DNA activity/effect such as a) thermal denaturation study, and b) DNA intercalator/unwinding assay.
The results for estimation of mean inhibitory concentration (IC50) for different investigated novel thiazole compounds (1A, 19A, R1, 11M and 12M) at different concentrations for each (40, 50, 60, 70, 80, 90, 100 and 110µg) were recorded as 66.87, 65.79, 74.97, 76.57 and 80.77µg respectively. The obtained results revealed that the compound 19A (IC50= 65.79µg) was the most inhibitory one. On the other hand compound 12M (IC50= 80.77 µg) was the least inhibitory one. Concerning the previous result 12M is the safest one.
The obtained results regarding the effect of novel thiazole compounds (1A, 19A, R1, 11M and 12M) at different concentrations for each (128, 64, 32 and 16 µg) showed a significant decrease in the % of ATP luminescence at 128 and 64 µg respectively compared to the negative control DMSO. While the novel thiazole compound 11M showed a significant decrease in the % of ATP luminescence at 128 µg compared to the negative control DMSO. On the other hand the novel thiazole compound 12M showed no significant decrease in the % of ATP luminescence at any concentration compared to the negative control DMSO.
The recorded result for the effect of novel thiazole compounds (1A, 19A, R1, 11M and 12M) on membrane permeability of murine mammalian cells (J774A.1) indicated by % of stained cells showed no propidium Iodide dye uptake in all cells treated by the all novel thiazole compounds compared to the positive control TritonX-100.
The recorded result for the effect of novel thiazole compounds (1A, 19A, R1, 11M and 12M) on DNA thermal denaturation showed no DNA thermal denaturation of all the novel thiazoles compared to the positive control Amsacrine which is a known DNA intercalator.
The recorded results for the effect of novel thiazole compounds (1A, 19A, R1, 11M and 12M) on DNA intercalator/unwinding study showed In the absence of DNA intercalation, relaxed plasmid migrates as a series of discrete topomers bands, with a characteristic ladder pattern which is shown in all novel thiazoles compounds. In contrast, intercalation agents such as Amsacrine results in a change in linking number, resulting in a change in the migration pattern (supercoiled).
Taken altogether, thestudy indicated that novel thiazole compounds exhibit good safety profile and warrant further development and improvement.