Table 3.
Molecular docking of Cannabis sativa L. compounds.
| Enzyme | Ligand | Docking Tool |
Score (kcal/mol) |
Reference | ||||
|---|---|---|---|---|---|---|---|---|
| Name | ID (pdb = p / Unipr = up) |
Class of Protein |
Biological Activity |
Name | Class of Metabolite |
|||
| Acetylcholine esterase (ACHE) | 1EVE (p) | Hydrolase | Pesticidal | Cannabioxepane | Cannabinoids | AutoDock vina | –10.4 | [127] |
| Δ-9-THCA | Cannabinoids | –10.3 | ||||||
| Δ-8-THC | Cannabinoids | –10.1 | ||||||
| CBN | Cannabinoids | –10.1 | ||||||
| CBT | Cannabinoids | –9.8 | ||||||
| CBD | Cannabinoids | –9.8 | ||||||
| CBL | Cannabinoids | –9.6 | ||||||
| Isocannabispiradienone | Cannabinoids | –9.4 | ||||||
| CBC | Cannabinoids | –9.4 | ||||||
| CBCA | Cannabinoids | –9.3 | ||||||
| CBGA | Cannabinoids | –9.2 | ||||||
| Cannabispiradienone | Terpenes | –9.2 | ||||||
| Cannabispirol | Polyphenols | –9.2 | ||||||
| Butyrylcholinesterase (BCHE) |
1P0I (p) | Hydrolase | Pesticidal | Cannabioxepane | Cannabinoids | AutoDock vina | –9.8 | [127] |
| CBL | Cannabinoids | –8.9 | ||||||
| CBN | Cannabinoids | –8.8 | ||||||
| CBT | Cannabinoids | –8.7 | ||||||
| Δ-8-THC | Cannabinoids | –8.7 | ||||||
| CBL | Cannabinoids | –8.4 | ||||||
| Isocannabispiradienone | Cannabinoids | –8.3 | ||||||
| CBD | Cannabinoids | –8.2 | ||||||
| Cannabispiradienone | Terpenes | –8.2 | ||||||
| Cannabispiran | Polyphenols | –8.2 | ||||||
| Acetylcholine esterase (ACHE) | 1EVE (p) | Hydrolase | Pesticidal | CBD | Cannabinoids | AutoDock vina | −14.38 | [128] |
| CBN | Cannabinoids | −13.91 | ||||||
| Δ-9-THC | Cannabinoids | −13.82 | ||||||
| Plasmodium falciparum dihydrofolate reductase-thymidinesynthase (pfdhfr-ts) | 1J3I (p) | Lyase | Antimalarial | 7-oxo-9a-hydroxyhexahydrocannabinol | Cannabinoids | AutoDock vina | −9.40 | [129] |
| 10ar-hydroxyhexahydrocannabinol | Cannabinoids | −9.20 | ||||||
| 10-oxo-delta6a,10a-tetrahydrocannabinol | Cannabinoids | −9.20 | ||||||
| 8-oxo-delta9-tetrahydrocannabinol | Cannabinoids | −9.10 | ||||||
| 10a-hydroxyhexahydrocannabinol | Cannabinoids | −9.10 | ||||||
| Leishmania major pteridine reductase 1 (lmajptr1) | 1E7W, 1W0C, 2BF7 and 3H4V (p) | Oxido-reductase | Anti-leishmania | 4,5,4’5’-dimethylenedioxy-3,3’-dimethoxy-7,7’-epoxylignan | Polyphenols | Molegro virtual docker | −35.01 | [130] |
| Cannflavin A | Flavonoids | −34.42 | ||||||
| Leishmania mexicana glycerol-3-phosphate dehydrogenase (lmexgpdh) | 1EVZ, 1M66, 1N1E and 1N1G (p) | Oxido-reductase | Anti-leishmania | 4-terpenylcannabinolate | Cannabinoids | Molegro virtual docker | −35.90 | [130] |
| 3’-o-methyldiplacone | Flavonoids | −35.44 | ||||||
| 4’-o-methyldiplacone | Flavonoids | −34.18 | ||||||
| Sophoronol E | Flavonoids | −33.89 | ||||||
| Leishmania major methionyl-transynthetase (lmajmetrs) | 3KFL (p) | Ligase | Anti-leishmania | 4,6-dibenzoyl-2-[phenylhydroxymethyl]-3(2h)-benzofuranone | Polyphenols | Molegro virtual docker | −38.81 | [130] |
| Leishmania donovani cyclophilin (ldoncyp) | 2HAQ and 3EOV (p) | Isomerase | Anti-leishmania | 3’-o-methyldiplacone | Flavonoids | Molegro virtual docker | −30.23 | [130] |
| Leishmania major oligopeptidase b (lmajopb) | 2XE4 (p) | Protease | Anti-leishmania | 3-methoxycitrunobin-4-methyl ether | Polyphenols | Molegro virtual docker | −30.74 | [130] |
| 4’-o-methylglycyrrhisoflavone | Flavonoids | −30.47 | ||||||
| Leishmania major uridine 2p-glucose pyrophosphorylase (lmajugpase) | 2OEF and 2OEG (p) | Transferase | Anti-leishmania | 4’,6-dihydroxy-2-[phenylmethylene]-3(2h)-benzofuranone | Polyphenols | Molegro virtual docker | −33.94 | [130] |
| Leishmania major n-myristoyl-transferase (lmajnmt) | 2WSA, 3H5Z and 4A30 (p) | Transferase | Anti-leishmania | Diplacone | Flavonoids | Molegro virtual docker | −32.43 | [130] |
| Trans-4-isopentenyl-3,5,2,4 -tetrahydroxystilbene | Polyphenols | −30.45 | ||||||
| Leishmania infantum nicotinamidase (linfpnc1) | 3R2J (p) | Hydrolase | Anti-leishmania | 5,8-dihydroxy-1-hydroxymethylnaphtho-[2,3-c] furan-4,9-dione | Polyphenols | Molegro virtual docker | −23.45 | [130] |
| Umckalin | Polyphenols | −21.85 | ||||||
| Scoparone | Flavonoids | −21.77 | ||||||
| Leishmania major dihydroorotate dehydrogenase (lmajdhodh) | 3GYE, 3MHU and 3MJY (p) | Oxido-reductase | Anti-leishmania | Aristolignin | Flavonoids | Molegro virtual docker | −31.21 | [130] |
| Crotaorixin | Flavonoids | −31.84 | ||||||
| Mammea B/BA | Polyphenols | −29.09 | ||||||
| Leishmania mexicana pyruvate kinase (lmexpyk) | 1PKL, 3HQP and 3PP7 (p) | Protein kinase | Anti-leishmania | Kusunokinin | Polyphenols | Molegro virtual docker | −31.19 | [130] |
| Leishmania major phosphodiesterase 1 (lmajpde1) | 2R8Q (p) | Hydrolase | Anti-leishmania | Machaeriol B | Cannabinoids | Molegro virtual docker | −28.97 | [130] |
| Leishmania major tyrosyl-trna synthetase (lmajtyrrs) | 3P0H and 3P0J (p) | Ligase | Anti-leishmania | Bractein triacetate | Polyphenols | Molegro virtual docker | −33.08 | [130] |
| COVID-19 protease | 6LU7 (p) | Protease | Antiviral | CBD | Cannabinoids | AutoDock vina | −7.10 | [131] |
| Hiv-1 protease | ND | Protease | Antiviral | Cannflavin | Flavonoids | AutoDock vina | −9.70 | [132] |
| Human angiotensin-converting enzyme (ACE2) | 1R4L (p) | Protease | Antiviral | THC | Cannabinoids | AutoDock vina | −9.2 | [133] |
| 2019-ncov spike protein s2 subunit | 6LXT (p) | Surface glycoprotein | Antiviral | THC | Cannabinoids | AutoDock vina | −4.2 | [133] |
| SARS-CoV-2 mpro | ND | Protease | Antiviral | Cannabisin A | Lignanamide | AutoDock vina | −12.76 | [134] |
| 3c-like protease (C) | 6LU7 (p) | Protease | Antiviral | Hesperidin | Flavonoids | AutoDock vina | −8.3 | [135] |
| Nabiximols | Cannabinoids | −8 | ||||||
| Spike glycoprotein (S) | 6VXX (p) | Surface glycoprotein | Antiviral | Hesperidin | Flavonoids | AutoDock vina | −10.4 | [135] |
| Nabiximols | Cannabinoids | −10.2 | ||||||
| Inhibitor of nuclear factor kappa-b kinase subunit β (IKKbeta) | 3BRT (p) | Inhibitor kappa kinase | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −7.99 | [136] |
| Mitogen-activated protein kinase 14 | 4IDT (p) | Map kinase | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −7.35 | [136] |
| Cellular tumor antigen p53 | IAIE (p) | Tumor suppressor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −6.08 | [136] |
| Nf-kappa-b inhibitor alpha | 1IKN (p) | Nfkb inhibitor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −5.82 | [136] |
| Tnf receptor-associated factor 6 | 1IB6 (p) | Traf protein | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −5.74 | [136] |
| Transcription factor p65 | 1NFI (p) | Nfkb inhibitor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −5.66 | [136] |
| Epidermal growth factor receptor | 1MOX (p) | Epidermal growth factor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −5.64 | [136] |
| Nf-kappa-b essential modulator | 3BRV (p) | Nfkb inhibitor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −5.36 | [136] |
| Rac-alpha serine/threonine-protein kinase | 1UNQ (p) | Transferase | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −5.34 | [136] |
| Mitogen-activated protein kinase 3 | 2O2V (p) | Map kinase | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −5.34 | [136] |
| Poly [adp-ribose] polymerase 1 | 2COK (p) | DNA polymerase | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −4.88 | [136] |
| Hypoxia-inducible factor 1-alpha | 1H2K (p) | Hypoxia inducible factor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −4.41 | [136] |
| Inhibitor of nuclear factor kappa-b kinase subunit a | 3BRT (p) | Inhibitor kappa kinase | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −4.32 | [136] |
| Nuclear factor kappa-b p105 subunit | IMDI (p) | Nfkb inhibitor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −4.23 | [136] |
| G1/s-specific cyclin-d1 | 5VZU (p) | Proto-oncogene regulator | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | −3.44 | [136] |
| Activator protein-1 (AP-1) | 1JUN (p) | Transcription factor | Anti-inflammatory | CBD | Cannabinoids | AutoDock-tools | -3.41 | [136] |
| Crystal structure of the DLC1 RhoGAP domain in liver cancer 1 | 3KUQ (p) | GTPase-activating proteins | Anticancer | CBC | Cannabinoids | Docking-server | −3.89 | [137] |
| THCV | Cannabinoids | −3.25 | ||||||
| CBGV | Cannabinoids | −3.21 | ||||||
| CBDA | Cannabinoids | −3.34 | ||||||
| Placental aromatase cytochrome p450 | 3EQM (p) | Cytochrome | Anticancer | CBDC1 | Cannabinoids | Molegro (Glide) | −9.03 | [138] |
| CBGV | Cannabinoids | −7.8 | ||||||
| CBCA | Cannabinoids | −7.73 | ||||||
| CBCVA | Cannabinoids | −7.45 | ||||||
| CBCV | Cannabinoids | −8.29 | ||||||
| CBDV | Cannabinoids | −8.34 | ||||||
| CBT | Cannabinoids | −7.86 | ||||||
| (Δ−9-THC) | Cannabinoids | −7.43 | ||||||
| CBR | Cannabinoids | −6.93 | ||||||
| Heat shock protein 90 (hsp90) | 2QG2 (p) | Chaperone protein | Anticancer | Guaiol | Terpenes | AutoDock vina | −10.80 | [139] |
| Topoisomerase II alpha | 5GWK (p) | Nuclear enzyme | Anticancer | 7-o-methylcyanidin | Flavonoids | Molegro (Glide) | −10.395 | [140] |
| Rutin | Flavonoids | −9.847 | ||||||
| Luteolin-7-o-glucoside | Flavonoids | −9.563 | ||||||
| Myricetin 7-glucoside | Flavonoids | −9.383 | ||||||
| Tumor necrosis factor-α (TNF-α) | 2E7A (p) | Tumor necrosis factor | Anticancer | Ascorbic acid | Vitamins | AutoDock vina | −5.4 | [141] |
| Linoleic acid | Terpenes | −3.8 | ||||||
| Tryptophan | Amino acids | −5.6 | ||||||
| Arachidonate 5-lypoxygenase | 5IR4 (p) | Lipoxygenase | Anticancer and anti-inflammatory | Δ-9-THC | Cannabinoids | Molecular operating environment | −4.57 | [142] |
| Δ-8-THC | Cannabinoids | −4.87 | ||||||
| CBC | Cannabinoids | −5.14 | ||||||
| CBG | Cannabinoids | −5.59 | ||||||
| CBL | Cannabinoids | −4.83 | ||||||
| CBD | Cannabinoids | −4.97 | ||||||
| Human myeloperoxidase (MPO) | 3F9P (p) | Peroxidase | Anti-inflammatory and degenerative processes | Peptide YGRDEISV | Proteins | Discovery studio | −114.6 | [143] |
| Peptide LDLVKPQ | Proteins | −82.8 | ||||||
| Angiotensin-converting enzyme (ACE) | 1O8A (p) | Protease | Hypertension | Peptide WVYY | Proteins | Accelrys discovery studio | −27.25 | [144] |
| Peptide WYT | Proteins | −21.99 | ||||||
| Renin | 2V0Z (p) | Protease | Hypertension | Peptide SVYT | Proteins | Accelrys discovery studio | −25.33 | [144] |
| Peptide WYT | Proteins | −19.12 | ||||||
| Angiotensin-converting enzyme (ACE) | 1O8A (p) | Protease | Hypertension | Peptide ALVY | Proteins | Accelrys discovery studio | −69.23 | [145] |
| Peptide LLVY | Proteins | −65.97 | ||||||
| Peptide LSTSTDVR | Proteins | −105.59 | ||||||
| Peptide LLAPHY | Proteins | −86.86 | ||||||
| Cannabinoid receptor 1 (CNR1) | P21554 (up) | G-protein coupled receptor | Epilepsy | 8b-hydroxy-δ9-trans-tetrahydrocannabinolate | Cannabinoids | Molegro (Glide) | −8.039 | [146] |
| Epilepsy | 10aa-hydroxy-10-oxo-d8-tetrahydrocannabinol | Cannabinoids | −8.52 | |||||
| Epilepsy | 10aα-hydroxyhexahydrocannabinol | Cannabinoids | −8.55 | |||||
| Epilepsy | CBNM | Cannabinoids | −8.761 | |||||
| Epilepsy | Cannabichromanone D | Cannabinoids | −8.446 | |||||
| Epilepsy | CBL | Cannabinoids | −8.336 | |||||
| Epilepsy | 5-acetoxy-6-geranyl-3-npentyl-1,4-benzoquinone | Cannabinoids | −8.571 | |||||
| Epilepsy | CBTC | Cannabinoids | −8.574 | |||||
| Androgen receptor (AR) | P10275 (up) | Nuclear receptor | Epilepsy | CBNM | Cannabinoids | Molegro (Glide) | −8.706 | [146] |
| Epilepsy | 5-acetoxy-6-geranyl-3-npentyl-1,4-benzoquinone | Cannabinoids | −8.262 | |||||
| Epilepsy | CBTC | Cannabinoids | −8.015 | |||||
| Glycogen synthase kinase-3 beta (GSK3B) | P49841 (up) | Protein kinase | Epilepsy | 8a-hydroxy-δ9-trans-tetrahydrocannabinolate | Cannabinoids | Molegro (Glide) | −6.439 | [146] |
| Epilepsy | 8b-hydroxy-δ9-trans-tetrahydrocannabinolate | Cannabinoids | −5.876 | |||||
| Epilepsy | CBL | Cannabinoids | −6.183 | |||||
| Albumin | P02768 (up) | Albumin | Epilepsy | (-)-trans-10-ethoxy-9-hydroxy-d6a(10a)-tetrahydrocannabinol | Cannabinoids | Molegro (Glide) | −6.429 | [146] |
| Epilepsy | CBNM | Cannabinoids | −6.306 | |||||
| Epilepsy | CBL | Cannabinoids | −6.057 | |||||
| Neurokinin 3 receptor (NK3R) | 1F88 (p) | Neurokinin receptor | Neuro-protective | CBD | Cannabinoids | AutoDock | −6.72 | [147] |
| CBG | Cannabinoids | −10.36 | ||||||
| Angiotensin-converting enzyme 2 (ACE2) | 6CS2 (p) | Protease | Neuro-protective | CBD | Cannabinoids | AutoDock vina | −8.9 | [148] |
| Interleukin-6 (IL6) | 1ALU (p) | Cytokine | Neuro-protective | CBD | Cannabinoids | AutoDock vina | −8.2 | [148] |
| Transmembrane protease serine 2 (TMPRSS2) | 3NPS (p) | Protease | Neuro-protective | CBN | Cannabinoids | AutoDock vina | −8.7 | [148] |
| Nrp1 protein | 7BP6 (p) | Semaphorin receptor | Neuro-protective | CBN | Cannabinoids | AutoDock vina | −8.5 | [148] |
| Tyrosine phosphatase-1b (PTP1B) | 1NWE (p) | Hydrolase | Dermo-cosmetic | Chrysophanol | Polyphenols | Charmm-based docker | −24.34 | [149] |
| P glycoprotein (P-GP) | 4Q9H (p) | GTPase | Multi-drug resistance | Cannabisin M | Lignanamide | AutoDock vina | −10.2 | [150] |
| Cannabisin N | Lignanamide | −10.2 | ||||||
| Cannabisin A | Lignanamide | −10.1 | ||||||
| Cannabisin B | Lignanamide | −10.1 | ||||||
| Cannabisin C | Lignanamide | −10.1 | ||||||
| Cannabisin D | Lignanamide | −10.1 | ||||||
Cannabichromene (CBC); cannabichromenic acid (CBCA); cannabichromevarin (CBCV); cannabichromevarinic acid (CBCVA); cannabicitran (CBTC); cannabicoumaronone (CBCN); cannabicyclol (CBL); cannabidiol (CBD); cannabidiol-c4 (CBDC4); cannabidiolic acid (CBDA); cannabidiorcol (CBDC); cannabidivarin (CBDV); cannabielsoin (CBE); cannabielsoin (CBL); cannabigerol (CBG); cannabigerolic acid (CBGA); cannabigerovarin (CBGV); cannabinodiol (CBND); cannabinodivarin (CBVD); cannabinol (CBN); cannabinol methyl ether (CBNM); cannabiripsol (CBR); cannabitriol (CBT); cannabivarin (CVN); tetrahydrocannabinol (THC); tetrahydrocannabivarin (THCV); δ-8-tetrahydrocannabinol (Δ-8-THC); δ-9-tetrahydrocannabinol (Δ-9-THC); δ9-tetrahydrocannabinolic acid (Δ-9-THCA).