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

Year 2024, Issue: Special Issue / International Multidisciplinary Symposium on Drug Research and Development, DRD-2023, 1 - 10, 01.07.2024

Pelin Nur Üçkan , Gülşah Karakaya , Beyza Düzleyen , Canan Sevimli Gür , Mutlu Aytemir

https://doi.org/10.52794/hujpharm.1374319

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

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

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