Phthalate monoesters are important metabolites of phthalate esters (PAEs) which have been extensively utilized in industry. This study aims to investigate the inhibition of phthalate monoesters on the activity of various isoforms of UDP-glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of environmental endocrine disruptors from the new perspectives. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human UGT isoforms. 100 μM phthalate monoesters exhibited negligible inhibition towards the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A10, UGT2B4, UGT2B7, UGT2B15 and UGT2B17. The activity of UGT1A7 was strongly inhibited by monoethylhexyl phthalate (MEHP), but slightly inhibited by all the other phthalate monoesters. UGT1A9 was broadly inhibited by monobenzyl phthalate (MBZP), monocyclohexyl phthalate (MCHP), MEHP, monohexyl phthalate (MHP) and monooctyl phthalate (MOP), respectively. MEHP exhibited competitive inhibition towards UGT1A7, and MBZP, MCHP, MEHP, MHP and MOP showed competitive inhibition towards UGT1A9. The inhibition kinetic parameters (K_i) were calculated to be 11.25 μM for MEHP-UGT1A7, and 2.13, 0.09, 1.17, 7.47, 0.16 μM for MBZP-UGT1A9, MCHP-UGT1A9, MEHP-UGT1A9, MHP-UGT1A9, MOP-UGT1A9, respectively. Molecular docking indicated that both hydrogen bonds formation and hydrophobic interactions significantly contributed to the interaction between phthalate monoesters and UGT isoforms. All these information will be beneficial for understanding the adverse effects of PAEs.

邻苯二甲酸单酯是邻苯二甲酸酯（PAE）的重要代谢产物，已广泛用于工业中。这项研究旨在研究邻苯二甲酸单酯对UDP-葡萄糖醛酸糖基转移酶（UGTs）各种同工型的抑制作用，试图从新的角度阐明环境内分泌干扰物的毒性机制。体外重组UGTs催化4-甲基伞形酮（4-MU）的葡萄糖醛酸苷化反应，以评估11种主要的人类UGT同工型中的8种邻苯二甲酸单酯。100μM邻苯二甲酸单酯对UGT1A1，UGT1A3，UGT1A6，UGT1A8，UGT1A10，UGT2B4，UGT2B7，UGT2B15和UGT2B17的抑制作用微不足道。邻苯二甲酸单乙基己酯（MEHP）强烈抑制了UGT1A7的活性，但所有其他邻苯二甲酸单酯均略微抑制了UGT1A7的活性。UGT1A9分别被邻苯二甲酸单苄基酯（MBZP），邻苯二甲酸单环己基酯（MCHP），MEHP，邻苯二甲酸单己酯（MHP）和邻苯二甲酸单辛酯（MOP）广泛抑制。MEHP对UGT1A7表现出竞争抑制作用，而MBZP，MCHP，MEHP，MHP和MOP对UGT1A9表现出竞争抑制作用。抑制动力学参数（K _i）对于MEHP-UGT1A7计算为11.25μM，对于MBZP-UGT1A9，MCHP-UGT1A9，MEHP-UGT1A9，MHP-UGT1A9，MOP-UGT1A9分别计算为2.13、0.09、1.17、7.47、0.16μM。分子对接表明，氢键形成和疏水性相互作用均显着促进了邻苯二甲酸酯单酯与UGT同工型之间的相互作用。所有这些信息将有助于理解PAE的不利影响。