ABSTRACT Three sets of differentphenylene-bis(hydrazone) derivatives namely,Gc, Gd and Ge,were designed, synthesized and evaluated for their molecular properties andin vitro anticancer activity against human osteosarcoma MG-63 cells. All compounds showed potent anticancer activity against the MG63 cells with IC50ranging from 18.27 to 21.68µM. Among three sets of compounds,Ge showed the most potent anticancer activity against osteosarcoma MG63 cells and was superior to standard anticancer reference drug,methotrexate (MTX). All compounds were characterized by spectroscopic studies (FTIR, 1H NMR, and13C NMR). In silicomolecular properties and drug-like properties were predicted by using Osiris property explorer software. None of Gc and Ge set of compounds violated Lipinski’s boundaries thereby suggesting good oral bioavailability. All the synthesized compounds possessed good pharmacokinetic properties in terms of absorption, distribution, metabolism and toxicity (ADMET). However, the GdSeries compoundswere predicted to be capableof crossing BBB due to their high lipophilicity. The Gc and Ge series of compounds showed good pharmacokinetic parameters within the acceptable range. All the synthesized drugs were predicted to have better pharmacokinetic properties thanthe MTX reference drug.Taken together, our study suggests that Ge series derivatives may be considered as lead drug molecules for possible anticancer applications to be useful against osteosarcoma.