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Pregled bibliografske jedinice broj: 873190

Novel amidino substituted benzimidazole and benzothiazole benzo[b]thieno-2-carboxamides exert strong antiproliferative and DNA binding properties


Cindrić, Maja; Jambon, Samy; Harej, Anja; Depauw, Sabine; David-Cordonnier, Marie-Hélène; Kraljević Pavelić, Sandra; Karminski-Zamola, Grace; Hranjec, Marijana
Novel amidino substituted benzimidazole and benzothiazole benzo[b]thieno-2-carboxamides exert strong antiproliferative and DNA binding properties // European journal of medicinal chemistry, 136 (2017), 468-479 doi:10.1016/j.ejmech.2017.05.014 (međunarodna recenzija, članak, znanstveni)


Naslov
Novel amidino substituted benzimidazole and benzothiazole benzo[b]thieno-2-carboxamides exert strong antiproliferative and DNA binding properties

Autori
Cindrić, Maja ; Jambon, Samy ; Harej, Anja ; Depauw, Sabine ; David-Cordonnier, Marie-Hélène ; Kraljević Pavelić, Sandra ; Karminski-Zamola, Grace ; Hranjec, Marijana

Izvornik
European journal of medicinal chemistry (0223-5234) 136 (2017); 468-479

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Amidines, antiproliferative activity, benzimidazoles, benzo[b]thieno-2-carboxamides, benzothiazoles, DNA binding, topoisomerase poisoning

Sažetak
Within this manuscript design, synthesis of novel 2-imidazolinyl substituted benzo[b]thieno-2-carboxamides bearing either benzimidazole or benzothiazole subunit and biological activity are presented and described. The antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity while cytotoxicity on normal fibroblasts was lower in comparison with 5- fluorouracile. The variations of 2-imidazolinyl substituent at heteroaromatic subunits in different positions led to different cytotoxic properties. The strongest selective activity against HeLa cells was observed for the benzothiazole derivative 4d with 2-imidazolinyl group at the benzo[b]thiophene subunit with a corresponding IC50 = 1.16 M. Additionally, several biological experiments were performed to explain the mode of biological action. Fluorescence microscopy evidenced nuclear subcellular localization of compounds 3a, 4a and 4c. Additionally, detailed DNA binding studies confirmed a strong DNA groove binding for derivatives 4a and 4c while DNase I footprinting experiments evidenced sequence- selective binding of compound 4c in the A-T rich side. Furthermore, topoisomerase suppressive effect was for compounds 4a-4c.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
HRZZ-IP-2013-11-5596 - SINTEZA I CITOSTATSKA ISPITIVANJA BIBLIOTEKE NOVIH DUŠIKOVIH HETEROCIKLA (Silvana Raić-Malić, )

Ustanove
Fakultet kemijskog inženjerstva i tehnologije, Zagreb,
Sveučilište u Rijeci - Odjel za biotehnologiju

Citiraj ovu publikaciju

Cindrić, Maja; Jambon, Samy; Harej, Anja; Depauw, Sabine; David-Cordonnier, Marie-Hélène; Kraljević Pavelić, Sandra; Karminski-Zamola, Grace; Hranjec, Marijana
Novel amidino substituted benzimidazole and benzothiazole benzo[b]thieno-2-carboxamides exert strong antiproliferative and DNA binding properties // European journal of medicinal chemistry, 136 (2017), 468-479 doi:10.1016/j.ejmech.2017.05.014 (međunarodna recenzija, članak, znanstveni)
Cindrić, M., Jambon, S., Harej, A., Depauw, S., David-Cordonnier, M., Kraljević Pavelić, S., Karminski-Zamola, G. & Hranjec, M. (2017) Novel amidino substituted benzimidazole and benzothiazole benzo[b]thieno-2-carboxamides exert strong antiproliferative and DNA binding properties. European journal of medicinal chemistry, 136, 468-479 doi:10.1016/j.ejmech.2017.05.014.
@article{article, year = {2017}, pages = {468-479}, DOI = {10.1016/j.ejmech.2017.05.014}, keywords = {amidines, antiproliferative activity, benzimidazoles, benzo[b]thieno-2-carboxamides, benzothiazoles, DNA binding, topoisomerase poisoning}, journal = {European journal of medicinal chemistry}, doi = {10.1016/j.ejmech.2017.05.014}, volume = {136}, issn = {0223-5234}, title = {Novel amidino substituted benzimidazole and benzothiazole benzo[b]thieno-2-carboxamides exert strong antiproliferative and DNA binding properties}, keyword = {amidines, antiproliferative activity, benzimidazoles, benzo[b]thieno-2-carboxamides, benzothiazoles, DNA binding, topoisomerase poisoning} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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