Synthesis, Antitumor, and DNA Binding Behavior of Novel 4-(2-Hydroxyquinolin-3-yl)-6-Phenyl-5, 6 Dihydropyrimidin Derivatives in Aqueous Medium

Abstract

This article deals with the synthesis of 4-(2-hydroxyquinolin-3-yl)-6-phenyl-5,6-dihydropyrimidin derivatives (2a–f), on condensation with various aromatic aldehydes and ketones in aqueous ethanolic NaOH solution yielding the corresponding chalcones (3). These chalcones were further reacted with thiourea/urea in the presence of a base, which led to the formation of the titled derivatives (2a–f). The newly synthesized heterocyles were characterized by elemental analysis, FTIR, ¹HNMR, and electronic and mass spectral data. The compounds (2a and 2b) were evulated for in vitro cyctotoxicity against human breast adenocarcinoma cell (MCF-7). In MTT cytotoxicity studies, both quinolinde derivatives were found most effective. The binding interaction behavior of the compound (2a) and (2d) with calf thymus-DNA (CT-DNA) was studied by electronic spectra, viscosity measurements, and thermal denaturation studies. On binding to CT-DNA, the absorption spectrum underwent bathochromic and hypochromic shifts. The binding constant (K_b) observed 4.3 × 10⁵ M⁻¹ for (2a), and 3.8 × 10⁵ M⁻¹ for (2d) suggested that compound (2a) binds more strongly with base pairs than (2d).

Keywords:

• Quinoline
• Claisen Schmidt condensation
• antitumor activity
• MTT assay
• DNA binding
• viscosity measurements
• aqueous medium

D. S. L. thanks Indian Institute of Science Bangalore, Karnataka University Dharwad for providing spectral data. K. R. V. R. would like to thank associate professor Dr. Sreedhra Pai, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University for the in vitro antitumor activity; project students, Shilashree, Sindura, Vinaya, and Preyadhrshini Sathish; and Kuvempu University for awarding the research fellowship.