Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates

kulabaş, necla; GURBOGA, MERVE; Bingöl Özakpınar, Özlem; Liu, Jianyang; Jakobson, Per-Johan; Danış, Özkan; Ogan, Ayse; Küçükgüzel, İlkay

Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates

Necla KULABAŞ, (Marmara Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, İstanbul, Türkiye)

Merve GÜRBOĞA, (Marmara Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul, Türkiye)

Özlem BİNGÖL ÖZAKPINAR, (Marmara Üniversitesi, Eczacılık Fakültesi, Biyokimya Anabilim Dalı, İstanbul, Türkiye)

Jianyang LIU, (Rheumatology Division, Department of Medicine, Solna, Karolinska Institutet & Karolinska University Hospital, Stockholm, Sweden)

Per-Johan JAKOBSSON, (Rheumatology Division, Department of Medicine, Solna, Karolinska Institutet & Karolinska University Hospital, Stockholm, Sweden)

Özkan DANIŞ, (Marmara Üniversitesi, Fen Fakültesi, Kimya Bölümü, İstanbul, Türkiye)

Ayşe OĞAN, (Marmara Üniversitesi, Fen Fakültesi, Kimya Bölümü, İstanbul, Türkiye)

İlkay KÜÇÜKGÜZEL (Fenerbahçe Üniversitesi, Eczacılık Fakültesi, Farmasötik Kimya Anabilim Dalı, İstanbul, Türkiye)

FABAD Journal of Pharmaceutical Sciences

5 0

Yıl: 2023 Cilt: 48 Sayı: 3 Sayfa Aralığı: 395 - 410 Metin Dili: İngilizce İndeks Tarihi: 01-12-2023

Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates

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 Kelime: Paracetamol 1 2 4-triazole cancer mPGES-1 COX- 1/2

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, NMR (1H and 13C) ve kütle spektral verileri ile karakterize edildi. Beş insan kanser hücre hattına (akciğer kanseri A549, kronik miyelojenöz lösemi K562, meme kanseri MCF-7, prostat kanseri PC-3, 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 MTT yöntemiyle test edildi. Ek olarak, on iki hedef bileşik 9-20, mPGES-1 ve COX-1/2 inhibe edici etkileri 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 olmadıkları belirlendi. Son olarak yeni sentezlenen bileşiklerin ADMET özellikleri in siliko yöntemler kullanılarak tahmin edildi.

Anahtar Kelime: Parasetamol 1 2 4-triazol kanser mPGES-1 COX-1/2

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	kulabaş n, GURBOGA M, Bingöl Özakpınar Ö, Liu J, Jakobson P, Danış Ö, Ogan A, Küçükgüzel İ (2023). Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. , 395 - 410.
Chicago	kulabaş necla,GURBOGA MERVE,Bingöl Özakpınar Özlem,Liu Jianyang,Jakobson Per-Johan,Danış Özkan,Ogan Ayse,Küçükgüzel İlkay Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. (2023): 395 - 410.
MLA	kulabaş necla,GURBOGA MERVE,Bingöl Özakpınar Özlem,Liu Jianyang,Jakobson Per-Johan,Danış Özkan,Ogan Ayse,Küçükgüzel İlkay Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. , 2023, ss.395 - 410.
AMA	kulabaş n,GURBOGA M,Bingöl Özakpınar Ö,Liu J,Jakobson P,Danış Ö,Ogan A,Küçükgüzel İ Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. . 2023; 395 - 410.
Vancouver	kulabaş n,GURBOGA M,Bingöl Özakpınar Ö,Liu J,Jakobson P,Danış Ö,Ogan A,Küçükgüzel İ Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. . 2023; 395 - 410.
IEEE	kulabaş n,GURBOGA M,Bingöl Özakpınar Ö,Liu J,Jakobson P,Danış Ö,Ogan A,Küçükgüzel İ "Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates." , ss.395 - 410, 2023.
ISNAD	kulabaş, necla vd. "Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates". (2023), 395-410.

APA	kulabaş n, GURBOGA M, Bingöl Özakpınar Ö, Liu J, Jakobson P, Danış Ö, Ogan A, Küçükgüzel İ (2023). Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. FABAD Journal of Pharmaceutical Sciences, 48(3), 395 - 410.
Chicago	kulabaş necla,GURBOGA MERVE,Bingöl Özakpınar Özlem,Liu Jianyang,Jakobson Per-Johan,Danış Özkan,Ogan Ayse,Küçükgüzel İlkay Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. FABAD Journal of Pharmaceutical Sciences 48, no.3 (2023): 395 - 410.
MLA	kulabaş necla,GURBOGA MERVE,Bingöl Özakpınar Özlem,Liu Jianyang,Jakobson Per-Johan,Danış Özkan,Ogan Ayse,Küçükgüzel İlkay Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. FABAD Journal of Pharmaceutical Sciences, vol.48, no.3, 2023, ss.395 - 410.
AMA	kulabaş n,GURBOGA M,Bingöl Özakpınar Ö,Liu J,Jakobson P,Danış Ö,Ogan A,Küçükgüzel İ Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. FABAD Journal of Pharmaceutical Sciences. 2023; 48(3): 395 - 410.
Vancouver	kulabaş n,GURBOGA M,Bingöl Özakpınar Ö,Liu J,Jakobson P,Danış Ö,Ogan A,Küçükgüzel İ Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates. FABAD Journal of Pharmaceutical Sciences. 2023; 48(3): 395 - 410.
IEEE	kulabaş n,GURBOGA M,Bingöl Özakpınar Ö,Liu J,Jakobson P,Danış Ö,Ogan A,Küçükgüzel İ "Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates." FABAD Journal of Pharmaceutical Sciences, 48, ss.395 - 410, 2023.
ISNAD	kulabaş, necla vd. "Synthesis and Biological Evaluation of Novel Paracetamol-Triazole Conjugates". FABAD Journal of Pharmaceutical Sciences 48/3 (2023), 395-410.