Some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives overcome imatinib resistance by induction of apoptosis and reduction of P-glycoprotein activity

Basit Öğe Kaydı
dc.contributor.authorHekmatshoar, Yalda
dc.contributor.authorÖzkan, Tülin
dc.contributor.authorAlp, Mehmet
dc.contributor.authorGürkan-Alp, A. Selen
dc.contributor.authorSunguroğlu, Asuman
dc.date.accessioned2023-10-04T13:46:04Z
dc.date.available2023-10-04T13:46:04Z
dc.date.issued2023en_US
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri, Tıbbi Biyoloji Ana Bilim Dalıen_US
dc.description.abstractImatinib (IMA) is a tyrosine kinase inhibitor (TKI) introduced for the chronic myeloid leukemia (CML) therapy. Emergence of IMA resistance leads to the relapse and failure in CML therapy. Benzimidazole is a heterocyclic organic compound which is widely investigated for the development of anticancer drugs. In this study, we aimed to explore the anticancer effects of some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives on K562S (IMA-sensitive) and K562R (IMA-resistant) cells. To analyze the cytotoxic and apoptotic effects of the compounds, K562S, K562R, and L929 cells were exposed to increasing concentrations of the derivatives. Cytotoxic effects of compounds on cell viability were analyzed with MTT assay. Apoptosis induction, caspase3/7 activity were investigated with flow cytometry and BAX, BIM, and BAD genes expression levels were analyzed with qRT-PCR. Rhodamine123 (Rho-123) staining assays were carried out to evaluate the effect of compounds on P-glycoprotein (P-gp) activity. The hit compounds were screened using molecular docking, and the binding preference of each compounds to BCR-ABL protein was evaluated. Our results indicated that compounds triggered cytotoxicity, caspase3/7 activation in K562S and K562R cells. Rho-123 staining showed that compounds inhibited P-gp activity in K562R cells. Overall, our results reveal some benzimidazole derivatives as potential anticancer agents to overcome IMA resistance in CML.en_US
dc.identifier.citationHekmatshoar, Y., Ozkan, T., Alp, M., Gurkan‐Alp, A. S., & Sunguroglu, A. (2023). Some 2‐[4‐(1H‐benzimidazol‐1‐yl) phenyl]‐1H‐benzimidazole derivatives overcome imatinib resistance by induction of apoptosis and reduction of P‐glycoprotein activity. Chemical Biology & Drug Design, 102(6), 1521-1533.en_US
dc.identifier.endpage1533en_US
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285
dc.identifier.issue6en_US
dc.identifier.scopus2-s2.0-85171444228
dc.identifier.scopusqualityQ2
dc.identifier.startpage1521en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12939/4070
dc.identifier.volume102en_US
dc.identifier.wosWOS:001069287900001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorHekmatshoar, Yalda
dc.language.isoen
dc.relation.ispartofChemical Biology & Drug Design
dc.relation.isversionof10.1111/cbdd.14343en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBenzimidazoleen_US
dc.subjectChronic Myeloid Leukemiaen_US
dc.subjectDrug Resistanceen_US
dc.subjectImatiniben_US
dc.titleSome 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives overcome imatinib resistance by induction of apoptosis and reduction of P-glycoprotein activity
dc.typeArticle

Dosyalar

Lisans paketi
Listeleniyor 1 - 1 / 1
[ X ]
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu
Temel Tıp Bilimleri Bölümü Koleksiyonu
WoS İndeksli Yayınlar Koleksiyonu