Pregled bibliografske jedinice broj: 1237563
Synthesis, Antiproliferative Evaluation and QSAR Analysis of Novel Halogen- and Amidino-Substituted Benzothiazoles and Benzimidazoles
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
Profili:
Domagoj Šubarić
(autor)
Livio Racane
(autor)
Vesna Rastija
(autor)
Valentina Rep Kaulić
(autor)
Silvana Raić-Malić
(autor)
Ljubica Glavaš Obrovac
(autor)
Marijana Jukić
(autor)
Citiraj ovu publikaciju:
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