Preliminary evaluation of acute cytogenotoxicity of a novel phenylboronic acid derivative; 2-(bromoacetamido) phenylboronic acid using the Allium cepa chromosome aberrations assay

Abstract

Phenylboronic acids and their conjugates as well as methods for their preparation and use have been the subject of several US patents. A novel phenylboronic acid derivative, 2-(bromoacetamido) phenylboronic acid (2-BAPBA), which may be useful in treatment of the human or animal diseases, has recently been prepared. Questions that need to be answered include: whether 2-BAPBA has any potential cytogenotoxic effects; and if so, whether they are commensurate with a reasonable risk/benefit ratio for its intended use. In this study, a well-established in vivo assessment bioassay, the Allium cepa test, was used to examine the effect of a dimethyl sulfoxide (DMSO) solution of 2-BAPBA at doses equivalent to 1/4, 1/2, 1 EC50 (half maximal effective concentration) and 2 EC50 (2.23, 4.45, 8.90, or 17.8 mg l^–1, respectively) for 24 or 48 h. The EC50 of 2-BAPBA was 8.9 mg l^–1. The compound was found to be cytotoxic, causing statistically significant reductions in root growth and mitotic index in a dose- and time-dependent manner. Furthermore, 2-BAPBA induced significant increases in the percentage of aberrant cells (% Abc) at all concentrations tested. It induced chromosome and nuclear aberrations, as well as morphological alterations in shape and size of cells, spindle disturbance and polar deviation in root tip meristem cells of Allium cepa. Under the present experimental conditions, 2-BAPBA is cytotoxic and genotoxic in onion root tips. The described work is the first of its type. To reach more definitive conclusions about this subject, further studies should be performed with different test systems.

Keywords:

• Allium cepa assay
• 2-(bromoacetamido) phenylboronic acid
• chromosome/nuclear aberrations
• micronucleus formation