Synthesis, spectroscopic characterizations and cytotoxic activities of some novel 1,2-bis-(tetrasubstituted-benzylidene) hydrazine analogues

Abstract

ABSTRACT. The present work describes an efficient and convenient synthesis of a library of novel 1, 2-bis-(tetrasubstituted-benzylidene) hydrazine an analogue (3-7) 1,2-bis (3-methoxy-2-hydroxybenzlidene) hydrazine (3) and 1,2-bis (6-bromo-3-methoxy 2-hydroxybenzylidene) hydrazine (4), were obtained via opening of ester coumarin derivatives (1 and 2) with hydrazine hydrate under reflux. Diazotization of compound 4 with aryldiazonium chloride led to the formation of 1,2-bis (6-bromo-5-arylazo-3-methoxy-2-hydroxybenzylidene) hydrazine (6a,b). Acetylation of compounds 4 and 6a with acetic anhydride afforded the corresponding 1,2-bis (6-bromo-5-substituted-3-methoxy-2-acetoxy benzylidene) hydrazines (5 and 7). The cytotoxicity screening of some synthesized 1,2-bis (tetra substituted benzylidene) hydrazines (4-7) against breast cancer cell lines (MCF-7), and it was found several active compounds. Meanwhile compound 5 exhibited cytotoxic activity compared to reference drug. The DNA flow cytometry on MCF-7 cells of compound 5 was determined, it was found to cause G2/M phase arrest and induce apoptosis in all G1/M phases. In addition, compound 5 has been tested in other trials against aromatase inhibitors and tyrosinase inhibitors.

KEY WORDS: Synthesis, Hydrazine derivatives, ¹H NMR, Mass spectra, MCF-7 cell lines, Cytotoxicity

Bull. Chem. Soc. Ethiop. 2023, 37(6), 1503-1520.
DOI: https://dx.doi.org/10.4314/bcse.v37i6.16