Medicinal Chemistry Research

, Volume 23, Issue 1, pp 76–86 | Cite as

Synthesis, molecular docking of novel 1,8-naphthyridine derivatives and their cytotoxic activity against HepG2 cell lines

  • Ahmad F. EweasEmail author
  • Nagy M. Khalifa
  • Nisreen S. Ismail
  • Mohamed A. Al-Omar
  • Abdel Mohsen M. Soliman
Original Research


A series of novel 2,7-dimethyl-1,8-naphthyridine derivatives substituted with Mannich bases 2ad, N-β-glycosides 6ae, 7ae, Schiff’s bases 8ac, pyrazolone 9, and S-alkylated derivatives 10ac have been synthesized in good yields starting from 4-hydroxy-2,7-dimethyl-1,8-naphthyridine 1 through multi-step synthesis. The newly synthesized title compounds were evaluated for their HepG2 cell growth inhibition, the results revealed that all the tested compounds process inhibitory effects on the growth of HepG2 liver cancer cells. Compound 8b showed the highest inhibition activity against HepG2 cell line (IC50 equals 3.2 μg/mL) among all tested compounds. The results were compared to 5-Fluorouracil (5-FU) and doxorubicin as reference drugs, (IC50 5 and 3.56 μg/mL). Furthermore, molecular docking of compounds 3b, 6a, and 8b into the binding site of topoisomerase II was carried out. The results of the binding energy scores of these compounds were compared to the docking score of Vosaroxin, a known 1,8-naphthyridine derivative which is in clinical trials as potential anticancer drug. Compound 8b docking result revealed that it is the only tested compound that intercalate with DNA segment of the topoisomerase II, similar to Vosaroxin which was used as reference drug for docking comparison.

Graphical Abstract


2,7-Dimethyl-1,8-naphthyridine derivatives Sugar hydrazones Cytotoxic activity HepG2 cell line Molecular docking 


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ahmad F. Eweas
    • 1
    • 2
    Email author
  • Nagy M. Khalifa
    • 1
    • 3
  • Nisreen S. Ismail
    • 1
  • Mohamed A. Al-Omar
    • 3
    • 4
  • Abdel Mohsen M. Soliman
    • 1
  1. 1.Department of Medicinal ChemistryNational Research CentreCairoEgypt
  2. 2.Pharmaceutical Chemistry Department, College of PharmacyTaif UniversityTaifSaudi Arabia
  3. 3.Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud UniversityRiyadhSaudi Arabia
  4. 4.Pharmaceutical Chemistry DepartmentCollege of Pharmacy, King Saud UniversityRiyadhSaudi Arabia

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