Table 1.
The summary of studies on CYP1-ligand interactions.
| Cytochrome P450 | Ligand | Methods | Notes | References |
|---|---|---|---|---|
| CYP1A1 and other cytochromes | ||||
| CYP1A1 and CYP1A2 | Aromatic amines, heterocyclic amines, aromatic hydrocarbons (benzo(a)pyrenemethylcholantrene), phenacetin, furafylline, and 7-methoxyresorufin | Homology modeling based on the CYP102 crystal structure | Human, mouse, rabbit, and trout CYP sequences | [22] |
| CYP1A1 | 7-Ethoxyresorufin, 7-methoxyresorufin, and benzo[a]pyrene | Homology modeling | [28] | |
| CYP1A1, CYP1A2, and CYP1B1 | Rutaecarpine and its derivatives | Homology modeling | [29] | |
| CYP1A1 | Arachidonic acid and eicosopentaenoic acid | Homology modeling | Molecular docking explains regiospecificity of metabolism | [30] |
| CYP1A1 and CYP1A2 | 7-Methoxyresorufin and 7-ethoxyresorufin | Homology modeling | Active site mutations in human CYP1A1 and CYP1A2 | [31] |
| CYP1A1 and CYP1A2 | Dietary flavonoids | Homology modeling | [32] | |
| CYP1A1 | B[a]P, B[a]P-7R, 8R-dihydrodiol, B[a]P-7S, 8S-dihydrodiol, eicosapentaenoate, and arachidonate | Homology modeling | Regioselectivity | [33] |
| CYP1A1 | Ethoxyresorufin | Homology modeling | [34] | |
| CYP1A1 | B[a]P | Wild-type and exon 6 del CYP1A1 homology models | [35] | |
| CYP1A1, CYP1A2, and CYP1B1 | Alkoxyl derivatives of 7,8-dehydrorutaecarpine | Homology models based on the crystal structure of rabbit CYP2C5 | [36] | |
| CYP1A1 | B[a]P, TCB, and TCDD | Rat, human, scup, and killifish homology models | [37] | |
| CYP1A1 | Representative ligands: α-naphthoflavone and benzothiazole | Homology modeling | [38] | |
| CYP1A1 and CYP1A2 (CYP2A6 and CYP2B1) | Arylacetylenes | CYP1A2 crystal structure (PDB: 2HI4) and homology model of CYP1A1 | Distances of ligands to heme, Fe, and Phe residues were analyzed | [39] |
| CYP1A1 | Benzoxazoles and benzothiazoles | CoMFA, homology modeling, and molecular docking | [40] | |
| CYP1A1, CYP1A2, and CYP1B1 (CYP2C9 and CYP3A4) | 33 flavonoid derivatives | PDB: 2HI4 and homology models of CYP1A1 and CYP1B1 | Hydroxyl and methoxy derivatives of flavone more potent as CYP inhibitors | [41] |
| CYP1A1, CYP1A2, and CYP1B1 | Methoxyflavonoids | PDB: 2HI4 and homology models of CYP1A1 and CYP1B1 | Important amino acid residues | [42] |
| CYP1A1 and CYP2B1 | p-Aminophenol-succinic acid derivatives (acetylcholinesterase inhibitors) | Homology modeling of rat CYPs based on structures of CYP1A2 and CYP3A4 and molecular dynamics | Biological experiments on rat microsomes induced with 5,6-benzoflavone and phenobarbital | [43] |
| CYP1A1, CYP1A2, and CYP1B1 | 17-β-Estradiol | PDB: 2HI4 and homology models of CYP1A1 and CYP1B1 | Important amino acid residues | [44] |
| CYP1A1 | 3,3′,4,4′,5-Pentachlorobiphenyl | Homology modeling | Rat and human recombinant microsomes | [45] |
| CYP1A1 and CYP1B1 | Resveratrol and its derivatives | Homology modeling based on CYP1A2 crystal structure | [46] | |
| CYP1A1 and CYP1B1 | Dietary flavonoids | Homology models based on the structure of CYP1A2 (PDB: 2HI4) | [47] | |
| CYP1A1 and CYP1A2 (CYP1A6 and CYP2B1) | Flavone propargyl ethers | CYP1A2 crystal structure (PDB: 2HI4) and homology model of CYP1A1 | Flavone propargyl ethers are more potent inhibitors of CYP1A1 and CYP1A2 than the parent hydroxy flavones | [48] |
| CYP1A1 and CYP1A2 | Phenacetin and acetaminophen | CYP1A2 crystal structure (PDB: 2HI4) and homology model of CYP1A1 | Isoform-selective metabolism | [49] |
| CYP1A1 and CYP1B1 | Polycyclic aromatic hydrocarbons | Homology modeling | [50] | |
| CYP1A1 | Sulforaphane | The tertiary structure of CYP1A1 was generated with the combination methods of threading, ab initio modeling, and structural refinement | Sulforaphane failed to reduce the genotoxic effect of TCDD in yeast cells | [51] |
| CYP1A1 | Pyrimidobenzothiazole (NSC745689) | Homology modeling and molecular dynamics | [52] | |
| CYP1A1, CYP1A2, and CYP1B1 (CYP2A6 and CYP2B1) | Pyranoflavones | Molecular surface images generated from UCSF Chimera | [53] | |
| CYP1A1 and CYP1A2 | Ethynylflavones | PDB: 4I8V and PDB: 2HI4 | Selective inhibitory activity toward CYP1A1 | [54] |
| CYP1A1 | Polychlorinated dibenzo-p-dioxins and coplanar polychlorinated biphenyls | Homology modeling | Rat and human CYP1A1 | [55] |
| CYP1A1, CYP1A2, and CYP1B1 | Polymethoxystilbenes | PDB: 4I8V, PDB: 2HI4, and PDB: 3PM0 | Potent and selective inhibitory activity of 2,3′,4′-trimethoxy-trans-stilbene | [56] |
| CYP1A1, CYP1A2, and CYP1B1 | 30 drugs metabolized by CYPs | PDB: 4I8V, PDB: 2HI4, and PDB: 3PM0 | MetaSite | [57] |
| CYP1A1 and CYP1A2 | 22 aromatic hydrocarbons and 3 fluorogenic alkoxyaryl compounds | PDB: 4I8V and PDB: 2HI4 | CYP1A variants | [58] |
| CYP1A1, CYP1A2, and CYP1B1 | Alkoxyresorufins | Homology modeling | Baikal seal and human CYPs | [59] |
| CYP1A1, CYP1A2, and CYP1B1 | 5F-203, 5-aminoflavone, 17-β-estradiol, melatonin, debrisoquine, theophylline, clozapine, and lidocaine | PDB: 4I8V, PDB: 2HI4, and PDB: 3PM0 | Differences in substrate specificity among CYPs | [60] |
| CYP1A1 | Naringenin and dihydroxybergamottin | Rat homology model, human PDB: 4I8V, and molecular dynamics | [61] | |
| CYP1A1 | Compounds selected by virtual screening of databases | Database screening, Hypo1; metabolite prediction study, MetaSite software; molecular docking studies; and molecular dynamics simulations | Antiproliferative activity on MDA-MB-435 human cells and two lead compounds with antitumor activity against MDA-MB-435 line | [62] |
| CYP1A1, CYP1A2, and CYP1B1 | Polymethoxy- and methylthio-trans-stilbene derivatives | PDB: 4I8V, PDB: 2HI4, and PDB: 3PM0 | [63] | |
|
| ||||
| CYP1A2 and other cytochromes | ||||
| CYP1A2 | Caffeine and MeIQ | Homology model based on CYP BM3 crystal structure | [64] | |
| CYP1A2 (CYP2D6 and CYP3A4) | Selected substrates | Homology modeling | Substrate selectivity studies | [65] |
| CYP1A2 | 7-Methoxyresorufin | Homology model based on the crystal structure of CYP2C5 | Hydrogen bonds and π-π stacking with Phe226 | [66] |
| CYP1A2 (CYP2A6, CYP2C9, CYP3A4, and CYP2E1) | Caffeine, theophylline, acetanilide, phenacetin, 7-methoxycoumarin, 7-ethoxycoumarin, 3-cyano-7′-ethoxycoumarin, naproxen, tacrine, amitriptyline, clozapine, and 7-ethoxyresorufin | PDB: 2HI4 | Regioselectivity prediction of CYP1A2-mediated metabolism | [67] |
| CYP1A2 | Methoxyresorufin and ethoxyresorufin | CYP1A2 homology model and crystal structure PDB: 2HI4 and homology structures of CYP1A2 mutants | [68] | |
| CYP1A2 | Virtual screening of CYP1A2 ligands | PDB: 2HI4 and automated docking (Gold version 3.2) | Prediction of the site of metabolism | [69] |
| CYP1A2 | Structurally diverse CYP1A2 ligands (substrates and inhibitors) | PDB: 2HI4 and molecular dynamics | Versatility and plasticity of the CYP1A2 active site | [70] |
| CYP1A2 (CYP2C9) | Chrysin, 7,8-benzoflavone, 7-hydroxyflavone, and warfarin | PDB: 2HI4 and molecular dynamics | [71] | |
| CYP1A2 | Phenacetin | PDB: 2HI4 | Wild-type and mutant forms of enzyme | [72] |
| CYP1A2 | Virtual screening of 971 herb compounds | Pharmacophore searching and docking procedure to CYP1A2 crystal structure (PDB: 2HI4) | Herb-drug interactions | [73] |
| CYP1A2 (CYP2A6, CYP2C9, and CYP2D6) | PDB: 2HI4 and molecular dynamics | Flexibility at normal and high-pressure conditions (300 MPa) | [74] | |
| CYP1A2 and CYP1B1 | Polymethoxy-trans-stilbenes | PDB: 2HI4 and homology model of CYP1B1 | Potent and selective inhibitory activity of 2,4,2′,6′-tetramethoxy-trans-stilbene | [75] |
| CYP1A2 | 7,8-Benzoflavone, oroxylin, and wogonin | PDB: 2HI4, binding free energy analysis with the MM-PBSL method, and molecular dynamics | [76] | |
| CYP1A2 and CYP1B1 | 4′-Methylthio-trans-stilbene derivatives | PDB: 2HI4 and PDB: 3PM0 | [77] | |
| CYP1A2 | 7-Ethoxyresorufin | PDB: 2HI4, ensemble docking, and molecular dynamics | Phe186Leu mutation | [78] |
| CYP1A2 (CYP2C9, CYP2D6, and CYP3A4) | Kinase inhibitors | PDB: 2HI4 | Drug-drug interactions | [79] |
| CYP1A2 (CYP2A6, CYP2C9, CYP3A4, and CYP2E1) | Acetaminophen | Large-scale 2D umbrella sampling, PDB: 2HI4, and molecular dynamics | Regioselectivity | [80] |
| CYP1A2 | The initial structure of wild-type CYP1A2 (CYP1A2.1) constructed from the CYP1A2 crystal structure PDB: 2HI4, and CYP1A2 mutants constructed from CYP1A2.1 refined after molecular dynamics simulation | Influence of amino acid mutations on the 3D structure and dynamic properties of the enzyme | [81] | |
|
| ||||
| CYP1B1 | ||||
| CYP1B1 | 17-β-Estradiol, α-naphthoflavone, 7-ethoxycoumarin, 7-ethoxyresorufin, bufuralol, and benzo(a)pyrene-7,8-diol | Homology model based on the structure of CYP2C5 | Allelic variant effects on metabolism | [82] |
| CYP1B1 | 17-β-Estradiol | Molecular dynamics simulations of homology-modeled structures | PCG-associated mutants | [83] |
| CYP1B1 | 7,8-Benzoflavone derivatives | PDB: 3PM0; MOE docking program | Inhibitors that eliminate CYP1B1-mediated drug resistance | [16] |
B[a]P: benzo[a]pyrene; TCB: 2,3′,4,4′-tetrachlorobiphenyl; TCDD: tetrachlorodibenzo-p-dioxin; PCG: primary congenital glaucoma.