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Pregled bibliografske jedinice broj: 1237563

Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles


Rep Kaulić, Valentina; Racané, Livio; Leventić, Marijana; Šubarić, Domagoj; Rastija, Vesna; Glavaš-Obrovac, Ljubica; Raić-Malić, Silvana
Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles // International journal of molecular sciences, 23 (2022), 24; 15843, 35 doi:10.3390/ijms232415843 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 1237563 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles

Autori
Rep Kaulić, Valentina ; Racané, Livio ; Leventić, Marijana ; Šubarić, Domagoj ; Rastija, Vesna ; Glavaš-Obrovac, Ljubica ; Raić-Malić, Silvana

Izvornik
International journal of molecular sciences (1422-0067) 23 (2022), 24; 15843, 35

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

Ključne riječi
benzothiazoles ; benzimidazoles ; anticancer ; QSAR ; cell cycle perturbation ; mitochondrial membrane potential

Sažetak
Syntheses of 6-halogen-substituted benzothiazoles were performed by condensation of 4- hydroxybenzaldehydes and 2-aminotiophenoles and subsequent O-alkylation with appropriate halides, whereas 6-amidino-substituted benzothiazoles were synthesized by condensation of 5-amidino-2- aminothiophenoles and corresponding benzaldehydes. While most of the compounds from non-substituted and halogen-substituted benzothiazole series showed marginal antiproliferative activity on tested tumor cell lines, amidino benzazoles exhibited stronger inhibitory activity. Generally, imidazolyl benzothiazoles showed pronounced and nonselective activity, with the exception of 36c which had a strong inhibitory effect on HuT78 cells (IC50 = 1.6 µM) without adverse cytotoxicity on normal BJ cells (IC50 >100 µM). Compared to benzothiazoles, benzimidazole structural analogs 45a–45c and 46c containing the 1, 2, 3-triazole ring exhibited pronounced and selective antiproliferative activity against HuT78 cells with IC50 < 10 µM. Moreover, compounds 45c and 46c containing the methoxy group at the phenoxy unit were not toxic to normal BJ cells. Of all the tested compounds, benzimidazole 45a with the unsubstituted phenoxy central core showed the most pronounced cell growth inhibition on THP1 cells in the nanomolar range (IC50 = 0.8 µM ; SI = 70). QSAR models of antiproliferative activity for benzazoles on T cell lymphoma (HuT78) and non-tumor MDCK-1 cells elucidated the effects of the substituents at position 6 of benzazoles, demonstrating their dependence on the topological and spatial distribution of atomic mass, polarizability, and van der Waals volumes. A notable cell cycle perturbation with higher accumulation of cells in the G2/M phase, and a significant cell increase in subG0/G1 phase were found in HuT78 cells treated with 36c, 42c, 45a–45c and 46c. Apoptotic morphological changes, an externalization of phosphatidylserine, and changes in the mitochondrial membrane potential of treated cells were observed as well.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekti:
HRZZ-IP-2018-01-4682 - Novi spojevi temeljeni na bioizosterima purina za ispitivanje njihovih antitumorskih i antipatogenih djelovanja (PurBioCaPa) (Raić-Malić, Silvana, HRZZ - 2018-01) ( CroRIS)

Ustanove:
Fakultet agrobiotehničkih znanosti Osijek,
Tekstilno-tehnološki fakultet, Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb,
Medicinski fakultet, Osijek

Poveznice na cjeloviti tekst rada:

doi www.mdpi.com

Citiraj ovu publikaciju:

Rep Kaulić, Valentina; Racané, Livio; Leventić, Marijana; Šubarić, Domagoj; Rastija, Vesna; Glavaš-Obrovac, Ljubica; Raić-Malić, Silvana
Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles // International journal of molecular sciences, 23 (2022), 24; 15843, 35 doi:10.3390/ijms232415843 (međunarodna recenzija, članak, znanstveni)
Rep Kaulić, V., Racané, L., Leventić, M., Šubarić, D., Rastija, V., Glavaš-Obrovac, L. & Raić-Malić, S. (2022) Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles. International journal of molecular sciences, 23 (24), 15843, 35 doi:10.3390/ijms232415843.
@article{article, author = {Rep Kauli\'{c}, Valentina and Racan\'{e}, Livio and Leventi\'{c}, Marijana and \v{S}ubari\'{c}, Domagoj and Rastija, Vesna and Glava\v{s}-Obrovac, Ljubica and Rai\'{c}-Mali\'{c}, Silvana}, year = {2022}, pages = {35}, DOI = {10.3390/ijms232415843}, chapter = {15843}, keywords = {benzothiazoles, benzimidazoles, anticancer, QSAR, cell cycle perturbation, mitochondrial membrane potential}, journal = {International journal of molecular sciences}, doi = {10.3390/ijms232415843}, volume = {23}, number = {24}, issn = {1422-0067}, title = {Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles}, keyword = {benzothiazoles, benzimidazoles, anticancer, QSAR, cell cycle perturbation, mitochondrial membrane potential}, chapternumber = {15843} }
@article{article, author = {Rep Kauli\'{c}, Valentina and Racan\'{e}, Livio and Leventi\'{c}, Marijana and \v{S}ubari\'{c}, Domagoj and Rastija, Vesna and Glava\v{s}-Obrovac, Ljubica and Rai\'{c}-Mali\'{c}, Silvana}, year = {2022}, pages = {35}, DOI = {10.3390/ijms232415843}, chapter = {15843}, keywords = {benzothiazoles, benzimidazoles, anticancer, QSAR, cell cycle perturbation, mitochondrial membrane potential}, journal = {International journal of molecular sciences}, doi = {10.3390/ijms232415843}, volume = {23}, number = {24}, issn = {1422-0067}, title = {Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles}, keyword = {benzothiazoles, benzimidazoles, anticancer, QSAR, cell cycle perturbation, mitochondrial membrane potential}, chapternumber = {15843} }

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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