Yeni Hidroksipiranonların Sentezi ve Farklı Hücre Hatlarında Sitotoksisitelerinin Araştırılması

Abstract

Kojik asitten sentezlenen mannich bazlarının çok çeşitli biyolojik aktivitelere sahip olduğu çalışma grubumuz tarafından yapılan kapsamlı çalışmalarda tespit edilmiştir. Bu çalışmada antikanser aktivitesi yüksek olan bileşiklerden yola çıkılarak yeni antikanser etkili bileşikler sentezlenmiştir. Bileşiklerin yapıları spektroskopik yöntemler ve element analizleri kullanılarak belirlendi. Bileşiklerin sitotoksisite taraması, farklı insan kanser hücre dizileri üzerinde MTT deneyi ile yapıldı. İyodometil grubu taşıyan Bileşik 1, 8,11 ila 21,24 µg/mL aralığındaki IC50 değerleriyle dikkat çekici sitotoksisite gösterdi. Vero hücrelerindeki (Afrika yeşil maymun böbreği epiteli) IC50 değeri 100 µg/mL'nin üzerinde belirlendi, bu da sağlıklı hücrelere karşı düşük sitotoksisite anlamına gelir. Buna kıyasla SK-MEL hücreleri 12 kat daha az IC50 değerine sahiptir ve terapötik indeksi 12'nin üzerindedir. Daha önce sitotoksik ajan olarak bildirilen KOJI MG84'e ​​en yakın sitotoksik etkinlik Bileşik 1'deki SK-MEL hücre hattında 4 kat daha az sitotoksik aktivite ile gözlenmiştir.

Keywords

• kojik asit
• Mannich bazları
• sitotoksisite
• antikanser

Synthesis and Investigation of Cytotoxicity in Different Cell Lines of Novel Hydroxypyranones

Abstract

Mannich bases synthesized from kojic acid have been determined in extensive studies conducted by our study group that they have a wide variety of biological activities. In this study, new anticancer-active compounds were synthesized from compounds with high anticancer activity. The compounds’ structures were identified through the utilization of spectroscopic methods and elemental analyses. The cytotoxicity screening of the compounds were done by MTT assay on different human cancer cell lines including MCF-7 and MDA-MB-231 (human breast cancer), SK-MEL (human melanoma), HT-29 (human colon adenocarcinoma), A549 (human lung carcinoma) cell line.Compound 1 bearing iodomethyl moiety, showed remarkable cytotoxicity with IC50 values in the range of 8.11 and 21.24 μg/mL. The IC50 value on Vero (African green monkey kidney epithelial) is over 100 μg/mL which means low cytotoxicity against healthy cells. Compared to this, SK-MEL cells have 12 times less IC50 value, with a therapeutic index over 12. The closest cytotoxic effectivity to KOJI MG84 which is previously reported as a cytotoxic agent, is observed on the SK-MEL cell line in compound 1, with 4 times less cytotoxic activity.

Keywords

• kojic acid
• Mannich bases
• cytotoxicity
• anticancer

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