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Exploring the anticancer properties of a new nicotinamide analogue: Investigations into in silico analysis, antiproliferative effects, selectivity, VEGFR-2 inhibition, apoptosis induction, and migration suppression.
Eissa, Ibrahim H; Yousef, Reda G; Sami, Muhammad; Elkaeed, Eslam B; Alsfouk, Bshra A; Ibrahim, Ibrahim M; Husein, Dalal Z; Elkady, Hazem; Metwaly, Ahmed M.
Afiliación
  • Eissa IH; Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
  • Yousef RG; Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
  • Sami M; Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
  • Elkaeed EB; Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia. Electronic address: ekaeed@um.edu.sa.
  • Alsfouk BA; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
  • Ibrahim IM; Biophysics Department, Faculty of Science, Cairo University, Giza 12613, Egypt.
  • Husein DZ; Chemistry Department, Faculty of Science, New Valley University, El-Kharja 72511, Egypt.
  • Elkady H; Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt.
  • Metwaly AM; Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt; Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexan
Pathol Res Pract ; 252: 154924, 2023 Dec.
Article en En | MEDLINE | ID: mdl-37956639
BACKGROUND: This study focuses on the development and evaluation of (E)-N-(3-(1-(2-(4-bromobenzoyl)hydrazono)ethyl)phenyl)nicotinamide (BHEPN) as a potential inhibitor of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2). METHODS: Computational investigations as density function theory (DFT), docking, molecular dynamics (MD) simulations, and ADMET) in addition to in vitro (VEGFR-2 inhibition, cytotoxicity against HepG2 and MCF-7 cancer cell lines, selectivity index, cells cycle analysis, apoptosis investigation, and cells migration assay) studies were conducted. RESULTS: DFT calculations determined the three-dimensional structure and indicated the reactivity of BHEPN. Molecular docking, and MD simulations analysis showed the BHEPN's binding affinity and its potential as a VEGFR-2 inhibitor. ADMET assessments predicted BHEPN's safety and drug-like characteristics. In vitro investigations confirmed the inhibition of VEGFR-2 with an IC50 value of 0.320 ± 0.012 µM. BHEPN also exhibited remarkable cytotoxic effects against HepG2 and MCF-7 cancer cell lines, with IC50 values of 0.19 ± 0.01 µM and 1.18 ± 0.01 µM, respectively, outperforming Sorafenib's IC50 values (2.24 ± 0.06 µM and 3.17 ± 0.01 µM), respectively. Notably, BHEPN displayed a higher IC50 value of 4.11 ± 0 µM against the non-carcinogenic Vero cell lines, indicating selectivity index values of 21.6 and 3.4 against the tested cancer cell lines, respectively. In a flow cytometry assay, BHEPN induced HepG2 cell cycle arrest at the G1/S phase. Moreover, BHEPN increased the incidence of early and late apoptosis in HepG2 cell lines (from 1.38% and 0.22%) in control cells to (4.11-26.02%) in the treated cells, respectively. Additionally, the percentage of necrosis raised to 13.39%, in contrast to 0.62% in control cells. Finally, BHEPN was able to reduce the migration and wound healing abilities in HepG2 cells to 38.89% compared to 87.92% in untreated cells after 48 h. These in vitro results aligned with the computational predictions, providing strong evidence of BHEPN's efficacy and safety in anticancer applications. CONCLUSIONS: BHEPN is a promising candidate for the development of novel anticancer agents through further in vitro and in vivo investigations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor 2 de Factores de Crecimiento Endotelial Vascular / Antineoplásicos Límite: Humans Idioma: En Revista: Pathol Res Pract Año: 2023 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptor 2 de Factores de Crecimiento Endotelial Vascular / Antineoplásicos Límite: Humans Idioma: En Revista: Pathol Res Pract Año: 2023 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Alemania