Yordanka Ivanova

New heterocyclic chalcones. Part 6. Synthesis and cytotoxic activities of 5- or 6-(3-aryl- 2-propenoyl)-2(3H)-benzoxazolones

Abstract A number of chalcones bearing an oxazole cycle were synthesized by Claisen-Schmidt condensation of 5-acetyl-2(3H)-benzoxazolone or 6-acetyl-2(3H)-benzoxazolone and the appropriate aldehydes. The chalcones were evaluated for cytotoxic activity against several tumor cell lines – BV-173 (human B cell precursor leukemia), MCF-7 and MDA-MB-231 (human breast adenocarcinoma) using the MTT-dye reduction assay. The tested compounds exhibit concentration-dependent cytotoxic effects at micromolar concentrations. Exposure of the BV-173 tumor cell line to compound 3f results in strong mono- and oligonucleosomal fragmentation of genomic DNA, as evidenced by a ‘cell death detection’ ELISA kit, which unambiguously indicates that the induction of apoptosis is implicated in the cytotoxic mode of action of the tested compound.

6-[1-Acetyl-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-3-yl]-2(3H)-benzoxazolone

The title compound, 6-[1-acetyl-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-2(3H)-benzoxazolone, was synthesized by condensation of 6-[3-(4-methoxyphenyl)-2-propenoyl]-2(3H)-benzoxazolone (1) and hydrazine hydrate in acetic acid in 84% yield. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

(E)-3-Methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2 (3H)-benzothiazolone

The title compound, (E)-3-methyl-6-(3-oxo-3-(thiophen-2-yl)-1-propenyl)-2(3H)-benzothiazolone, was synthesized by Claisen-Schmidt condensation of 3-methyl-2(3H)-benzothiazolone-6-carbaldehyde with 2-acetylthiophene in 94% yield. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

(E)-3-Methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2(3H)-benzothiazolone

The title compound, (E)-3-methyl-6-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)-2(3H)-benzothiazolone, was synthesized by both an acid- and base-catalyzed aldol condensation of 3-methyl-6-acetyl-2(3H)-benzothiazolone and 3,4,5-trimethoxyacetophenone. The structure of the target compound was confirmed using 1H-NMR, 13C-NMR, IR, MS, and elemental analysis.

6-[(4-Chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-3-methyl-2(3H)-benzoxazolone

A new hybrid molecule containing a triazole and a benzoxazolone ring was synthesized. The structure of 6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl) methyl]-3-methyl-2(3H)-benzoxazolone was confirmed by IR, 1H-, 13C-NMR, MS and elemental analysis.

3-(2-Oxopropyl)-2(3H)-benzoxazolone

The title compound is an important intermediate for the preparation of 3,4- and 3,4,5-substituted 1-(2-hydroxy-phenyl)imidazolin-2-ones [1,2] and 6-methyl-4-(2-hydroxyphenyl)-1,2,4-triazin-3-ones [3].[...]