Synthesis of bioactive benzopyridazine derivatives as antiproliferative agents against different cancer cell lines

New bioactive benzopyridazine derivatives 5a-d and 7a,b were successfully synthesized as antiproliferative agents via nucleophilic substitution reaction of 1-chloro-4-phenyl benzopyridazine 1 with the aromatic diamines 2a,b respectively to form the free amines 3a,b, The free amines 3a,b coupled with phenyl isocyanates 4a, phenyl isothiocyanate 4b or 2-naphthalene sulfonyl chloride 6 to form 5a-d and 7a,b derivatives. The establishment of the synthesized benzopyridazine derivatives was affirmed via different spectroscopic methods. Moreover, the antiproliferative activity of the synthesized derivatives were investigated against different human cancer cell lines such as HCT-116, HepG-2, MCF-7. The new synthesized benzopyridazine derivatives were found to have promising antiproliferative agents against the three cancer cell lines compared to the reference drug doxorubicin. Notably, 5b-d were found to be more selective towards HepG-2 cancer cell line with IC50 :1.6, 1.5, 1.6 µM as well as 7a, b with IC50: 1.6, 1.8 µM respectively higher than doxorubicin with IC50: 3.8 µM. The selective toxicity of the synthesized derivatives was evaluated using BJ-1 normal cell showing low toxicity towards the healthy normal cells compared to the reference drug.