Evaluation of M86 and M87 compounds against lead, cadmium, and arsenic toxicity in 2D and 3D liver cell models.

Increasing environmental pollution increases the risk of human exposure to toxic metals. Therefore, there is a need for substances to protect individuals against the harmful effects caused by toxic metals. This study investigates the 1:1 and 1:2 mole ratios of 3-methoxy catechol with 1,4-phenyl diboronic acid, resulting in the synthesis of 1,4-bis(4-methoxybenzo[d][1,3,2]dioxaborol-2-yl)phenyl)boronic acid (M86) and 1,4-bis(4-methoxybenzo[d][1,3,2]dioxaborol-2-yl)benzene (M87), and evaluates their protective effects against lead (Pb), cadmium (Cd), and arsenic (As) toxicity in the THLE-2 liver cell line. The structures of synthesized compounds M86 and M87 were characterized by 1 H, 13 C NMR, LC-MS-IT-TOF, UV-Vis., FTIR. The biological activities of these compounds were evaluated by DPPH, ABTS, CUPRAC, anticholinesterase, antiurease and antithyrosinase tests. 2D and 3D cell models were used in THLE-2 cell line. The protective effects of M86 and M87 against Pb, Cd and As toxicity were examined by XTT test and ATP colorimetric method and IC50 values were determined. In antioxidant tests, it was observed that M86 and M87 exhibited high activity in ABTS, DPPH and CUPRAC tests compared to standard antioxidants α-tocopherol (α-TOC) and butylated hydroxytoluene (BHT). Enzyme inhibition tests showed that M86 and M87 significantly suppressed acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activities. These compounds were found to reverse the decrease in cell proliferation following Pb, Cd and As exposure. In conclusion, M86 and M87 have the potential to be versatile therapeutic agents that provide effective protection against metal toxicity. In the future, with the evaluation of the efficacy of these compounds in in vivo models and clinical studies, it is thought that their use against metal toxicity may be possible.