Synthesis, characterization and biological evaluation of thioureas, acylthioureas and 4-thiazolidinones as anticancer and antiviral agents

Year 2017, Volume: 21 Issue: 2, 371 - 384, 01.04.2017

Necla Kulabaş Özlem Bingöl Özakpınar Derya Özsavcı Pieter Leyssen Johan Neyts İlkay Küçükgüzel

https://doi.org/10.12991/marupj.300913

Abstract

In this study, thiourea derivatives [1-4] were synthesized

by using 2-amino-4-substituted pyridine compounds and

these compounds have been used as the starting materials for

synthesis of 2-imino-1,3-thiazolidin-4-one ring [5, 6]. Two

different procedures for 4-thiazolidinone ring closure and

synthesis method were optimized. The synthesized compounds

were identified by the help of elemental analysis, IR, 1H-NMR,

13C-NMR and mass spectral data while the purities of them were

proved with TLC. Synthesized compounds were evaluated for

their antiviral and anticancer activity. Antiviral activity against

Murine norovirus, Yellow fever, Enterovirus and Chikungunya

strains of the test compounds were investigated and EC50 values

of these compounds were determined higher than 0,3 μM.

Cytotoxicity of test compounds was examined on NIH3T3

cell line. When the anticancer activity of test compounds was

examined against PC-3, A549, HeLa, HT-29, MCF-7, SJSA1

and K562 cell lines, the percent proliferation values of these

compounds were observed over 61% for all cell lines.

Keywords

Acylthioureas, anticancer, antiviral, tautomerism, thiourea, 2-amino-1, 3-thiazol-4-one, 2-imino-1, 3-thiazolidin- 4-one

Tiyoüreler, açiltiyoüreler ve 4-tiyazolidinonların sentezi, karakterizasyonu ve antikanser ve antiviral etkilerinin değerlendirilmesi

Abstract

Bu çalışma kapsamında 2-amino-4-sübstitüe piridin

bileşiklerinden hareketle sentezlenen tiyoüre türevleri [1-

4], 2-imino-1,3-tiyazolidin-4-on halkalarının [5, 6] sentez

başlangıç maddelerini oluşturmaktadır. 4-Tiyazolidinon halka

kapaması ve sentezi için iki farklı yöntem optimize edilmiştir.

Sentezlenen bileşiklerin yapıları elementel analiz, IR, 1H-NMR,

13C-NMR ve kütle spektrumu ile kanıtlanmış, saflıkları ise

İTK ile kontrol edilmiştir. Elde edilen bileşikler antiviral ve

antikanser etkinlikleri açısından değerlendirilmiştir. Murine

norovirus, Yellow fever, Enterovirus ve Chikungunya suşlarına

karşı antiviral etkileri incelenen bileşiklerin 0,3 μM’dan yüksek

EC50 değerine sahip oldukları tespit edilmiştir. Sitotoksisiteleri

NIH3T3 hücre hattı üzerinde incelenen bileşiklerin antikanser

etkileri PC-3, A549, HeLa, HT-29, MCF-7, SJSA1 ve K562

hücre hatlarına karşı incelenmiş %61’in üzerinde proliferasyon

değerine sahip oldukları gözlemlenmiştir.

Keywords

Açiltiyoüre; antikanser; antiviral; tautomerizm; tiyoüre; 2-amino-1, 3-tiyazol-4-on; 2-imino-1, 3- tiyazolidin-4-on

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