Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates

Yıl 2023, Cilt: 48 Sayı: 3, 395 - 410, 18.10.2023

Necla Kulabaş , Merve Gürboğa Özlem Bingöl Özakpınar , Jianyang Liu Per-johan Jakobsson Özkan Danış , Ayşe Ogan , İlkay Küçükgüzel

https://doi.org/10.55262/fabadeczacilik.1336831

Öz

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.

Anahtar Kelimeler

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

Destekleyen Kurum

TÜBİTAK

Proje Numarası

218S549

Teşekkür

This work was supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK - Grant no. 218S549) and European Union’s Horizon 2020 research project ArthritisHeal under the Marie Skłodowska-Curie grant agreement (No. 812890).

Yeni Parasetamol-Triazol Konjugatlarının Sentezi ve Biyolojik Değerlendirmesi

Öz

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

Proje Numarası

218S549

Kaynakça

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• 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.