Necla KULABAŞ, Merve GÜRBOĞA, Özlem BİNGÖL ÖZAKPINAR, Jianyang LİU, Per-johan JAKOBSSON, Özkan DANIŞ, Ayşe OGAN, İlkay KÜÇÜKGÜZEL

Yeni Parasetamol-Triazol Konjugatlarının Sentezi ve Biyolojik Değerlendirmesi

Başlangıç maddesi olarak parasetamol kullanılarak bazı yeni triazol içeren asetamid türevleri 9-20 sentezlendi ve yapıları FTIR, 1H-NMR, 13C-NMR ve kütle spektral verileri ile karakterize edildi. Beş kanser hücre hattına (insan akciğer kanseri A549, insan kronik miyelojenöz lösemi K562, insan meme kanseri MCF-7, insan prostat kanseri PC-3, insan nöroblastoma SH-SY5Y hücre hatları) karşı sentezlenen tüm moleküllerin in vitro sitotoksik aktiviteleri incelendi ve ayrıca seçiciliği tanımlamak için fare embriyonik fibroblast hücreleri (NIH/3T3) üzerinde sitotoksik etkileri test edildi. Bu in vitro aktivite çalışmalarında MTT testi kullanıldı. Ek olarak on iki hedef bileşik 9-20, mPGES-1 ve COX-1/2 inhibe edici aktiviteleri açısından tarandı. Sentezlenen bileşiklerin hiçbiri hem kanser hücrelerine hem de mPGES-1 ve COX-1/2 enzimlerine karşı anlamlı bir inhibisyon göstermezken, sağlıklı hücrelere karşı da sitotoksik olmakları belirlendi. Son olarak, yeni sentezlenmiş bileşiklerin ilaç benzeri özellikleri hesaplamalı yöntemlerle tahmin edilerek ADMET verileri sunuldu.

Anahtar Kelimeler:

parasetamol, 1, 2, 4-triazol, kanser, mPGES-1, COX-1/2

Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates

Some new triazole containing acetamide derivatives 9-20 using paracetamol as starting material were synthesized and their structure were characterized by FTIR, 1H-NMR, 13C-NMR and MS data. In vitro cytotoxic activities of all synthesized molecules against five cancer cell lines (human lung cancer A549, human chronic myelogenous leukemia K562, human breast cancer MCF-7, human prostate cancer PC-3, human neuroblastoma SH-SY5Y cell lines) were examined and were also tested their cytotoxic effect on mouse embryonic fibroblast cells (NIH/3T3) to define selectivity. MTT assay were used these in vitro activity studies. Additionally, twelve target compounds 9-20 were screened for their mPGES-1 and COX-1/2 inhibitory activities. While none of the synthesized compounds showed a significant inhibition against both cancer cells and mPGES-1 as well as COX-1/2, it was determined that they were not cytotoxic against healthy cells, too. Finally, ADMET data were presented by predicting the drug-like properties of newly synthesized compounds using computational methods.

Keywords:

paracetamol, 1, 2, 4-triazole, cancer, mPGES-1, COX-1/2,

PDF

___

Bülbül, B., Ding, K., Zhan, C. G., Çiftçi, G., Yelekçi, K., Gürboğa, M., … Küçükgüzel, İ. (2022). Novel 1,2,4-triazoles derived from Ibuprofen: synthesis and in vitro evaluation of their mPGES-1 inhibitory and antiproliferative activity. Molecular Diversity, (Early Access). https://doi.org/10.1007/ s11030-022-10551-0
Chang, H. H., Song, Z., Wisner, L., Tripp, T., Gokhale, V., & Meuillet, E. J. (2012). Identification of a novel class of anti-inflammatory compounds with anti-tumor activity in colorectal and lung cancers. Investigational New Drugs, 30, 1865–1877.