Molecular Docking Studies and the Effect of Fluorophenylthiourea Derivatives on Glutathione‐Dependent Enzymes

Abstract

Cancer is a serious problem affecting the health of all human societies. Chemotherapy refers to the use of drugs to kill cancer or the origin of cancer. In the past three decades, researchers have studied about proteins and their roles in the production of cancer cells. Glutathione S-transferases (GSTs) are a superfamily of enzymes that play a key role in cellular detoxification, protecting against reactive electrophiles attacks, including chemotherapeutic agents. Glutathione reductase (GR) is an important antioxidant enzyme involved in protecting the cell against oxidative stress. In this current study, GST and GR enzymes were purified from human erythrocytes using affinity chromatography. GR was obtained with a specific activity of 5.95 EU/mg protein and a 52.38 % yield. GST was obtained with a specific activity of 4.88 EU/mg protein and a 74.88 % yield. The effect of fluorophenylthiourea derivatives on the purified enzymes was investigated. Afterward, K I values were found to range from 23.04 � 4.37 μM-59.97 � 13.45 μM for GR and 7.22 � 1.64 μM -41.24 � 2.55 μM for GST. 1-(2,6difluorophenyl)thiourea was showed the best inhibition effect for both GST and GR enzymes. The relationships of inhibitors with 3D structures of GST and GR were explained by molecular docking studies.

The effects of morin and methotrexate on pentose phosphate pathway enzymes and GR/GST/TrxR enzyme activities: An in vivo and in silico study

“…[ 29 ] According to the previous studies regarding GR, the fluorophenylthiourea compounds displayed low µM IC 50 and K I values, with IC 50 values ranging from 8.85 ± 0.20 to 21.62 ± 0.27 µM and K I constants from 23.04 ± 4.37 to 59.97 ± 13.45 µM. [ 30 ] Li et al [ 31 ] investigated the time‐ and concentration‐dependent inhibition of yeast GR and human GR by phenethyl and benzyl isothiocyanates. The inhibiting effects of N ‐methylpyrrole derivatives on GR were described by Kocaoğlu et al [ 32 ] All the agents tested outperformed the potent GR inhibitor N , N ‐bis(2‐chloroethyl)‐ N ‐nitrosourea in terms of inhibitory efficacy, which researchers discovered.…”

Naringenin, Hesperidin and Quercetin Ameliorate Radiation‐Induced Damage In Rats: In Vivo And In Silico Evaluations

“…This enzyme is a crucial component of the defense system against dangerous substances. [75,76] Moreover, this lessens cellular damage brought on by toxic agents. In the current study, GST EU/mg values for eye tissue: quercetin (0.040 � 0.004) > naringenin (0.043 � 0.007) > quarcetin + RT (0.044 � 0.005) > naringenin + RT (0.061 � 0.004) > RT (0.079 � 0.006) > hesperidin (0.085 � 0.009) > normal control (0.110 � 0.013) > hesperidin + RT (0.115 � 0.007).…”

“…GST metabolizes toxins like carcinogens and possesses various functions, including antioxidant and anti‐inflammatory capabilities. This enzyme is a crucial component of the defense system against dangerous substances [75,76] . Moreover, this lessens cellular damage brought on by toxic agents.…”

Structure‐Activity Relationship of Methyl 4‐Aminobenzoate Derivatives as Being Drug Candidate Targeting Glutathione Related Enzymes: in Vitro and in Silico Approaches

“…Other authors investigated the in vitro primary effects of some active pharmaceutical ingredients on GST and GR enzymes, which are closely related to drug response in treating many diseases [42–44] . In some research, it was documented that antifungal, antibacterial, and antibiotic agents and calcium channel blockers showed high inhibition potency on hGSTpi [45–47] .…”