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Investigating the effect of polymerase inhibitors on cellular proliferation: Computational studies, cytotoxicity, CDK1 inhibitory potential, and LC-MS/MS cancer cell entrapment assays.
Farouk, Faten; Ibrahim, Ibrahim M; Sherif, Salma; Abdelhamed, Heba Gamal; Sharaky, Marwa; Al-Karmalawy, Ahmed A.
Afiliación
  • Farouk F; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
  • Ibrahim IM; Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt.
  • Sherif S; Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt.
  • Abdelhamed HG; Chemistry and Zoology Department, Faculty of Science, Cairo University, Giza, Egypt.
  • Sharaky M; Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
  • Al-Karmalawy AA; Biochemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt.
Chem Biol Drug Des ; 103(3): e14500, 2024 03.
Article en En | MEDLINE | ID: mdl-38467555
ABSTRACT
Directly acting antivirals (DAAs) are a breakthrough in the treatment of HCV. There are controversial reports on their tendency to induce hepatocellular carcinoma (HCC) in HCV patients. Numerous reports have concluded that the HCC is attributed to patient-related factors while others are inclined to attribute this as a DAA side-effect. This study aims to investigate the effect of polymerase inhibitor DAAs, especially daclatasivir (DLT) on cellular proliferation as compared to ribavirin (RBV). The interaction of DAAs with variable cell-cycle proteins was studied in silico. The binding affinities to multiple cellular targets were investigated and the molecular dynamics were assessed. The in vitro effect of the selected candidate DLT on cancer cell proliferation was determined and the CDK1 inhibitory potential in was evaluated. Finally, the cellular entrapment of the selected candidates was assessed by an in-house developed and validated LC-MS/MS method. The results indicated that polymerase inhibitor antiviral agents, especially DLT, may exert an anti-proliferative potential against variable cancer cell lines. The results showed that the effect may be achieved via potential interaction with the multiple cellular targets, including the CDK1, resulting in halting of the cellular proliferation. DLT exhibited a remarkable cell permeability in the liver cancer cell line which permits adequate interaction with the cellular targets. In conclusion, the results reveal that the polymerase inhibitor (DLT) may have an anti-proliferative potential against liver cancer cells. These results may pose DLT as a therapeutic choice for patients suffering from HCV and are liable to HCC development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis C / Carcinoma Hepatocelular / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Chem Biol Drug Des Asunto de la revista: BIOQUIMICA / FARMACIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis C / Carcinoma Hepatocelular / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: Chem Biol Drug Des Asunto de la revista: BIOQUIMICA / FARMACIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Reino Unido