Natural Product: NPC325871

Natural Product IDNPC325871
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,2,9,10-Tetramethoxy-6-Methyl-5,6,6A,7-Tetrahydro-4H-Dibenzo[De,G]Quinoline
IUPAC Name 1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL36536
PubChem CID 10145
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey RUZIUYOSRDWYQF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H25NO4/c1-22-7-6-12-9-18(25-4)21(26-5)20-14-11-17(24-3)16(23-2)10-13(14)8-15(22)19(12)20/h9-11,15H,6-8H2,1-5H3
SMILES CN1CCC2=CC(=C(C3=C2C1CC4=CC(=C(C=C43)OC)OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   355.18 Volume:   367.885
?
Van der Waals volume.
Dense:   0.965 LogP:   2.25
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.601
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.555
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   20.0
TPSA:   40.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.84 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.929 Fsp3:   0.429
MCE-18:   75.133
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.263 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.587
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.254
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.857

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.55 MDCK Permeability:   -4.654
Pgp-inhibitor:   0.758 Pgp-substrate:   0.333
PAMPA:   0.007
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.106
20% Bioavailability (F20%):   0.142 30% Bioavailability (F30%):   0.036
50% Bioavailability (F50%):   0.878

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.312 MRP1:   0.929
Plasma Protein Binding (PPB):   55.844% Volume Distribution (VD):   0.279
Fu: 37.495%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.808
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.975
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.518 CYP2C9-substrate:   0.034
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.005
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.136
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.007
HLM stability:   0.461
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  9.28 Half-life (T1/2):  3.263

ADMET: Toxicity

hERG Blockers:  0.573 hERG Blockers (10um):  0.709
Human Hepatotoxicity (H-HT):  0.432 Drug-induced Liver Injury (DILI):  0.01
AMES Toxicity:  0.608 Rat Oral Acute Toxicity:  0.551
Maximum Recommended Daily Dose:  0.807 Skin Sensitization:  0.879
Carcinogencity:  0.805 Eye Corrosion:  0.0
Eye Irritation:  0.038 Respiratory Toxicity:  0.969
Drug-induced Neurotoxicity:  0.723 Ototoxicity:  0.752
Hematotoxicity:  0.176 Drug-induced Nephrotoxicity:  0.072
Genotoxicity:  0.213 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.138 Hek293 Cytotoxicity:  0.465
BCF:   2.088
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.986
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.368
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.497
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20020118]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. DOI[10.1556/abot.45.2003.3-4.15]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[15019787]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22029392]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[22737858]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[23194502]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[23517479]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. root n.a. PMID[24317429]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[32058719]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[37685099]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. PMID[38415909]
NPO31490 Corydalis bulbosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24964 Dicentra eximia Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31490 Corydalis bulbosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24964 Dicentra eximia Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24964 Dicentra eximia Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30168 Thalictrum balcalense Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31490 Corydalis bulbosa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31183 Thalictrum foetidvm Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO827 Corydalis yanhusuo Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9498 Papaver somniferum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20441 Glaucium flavum Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24964 Dicentra eximia Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT3 Individual protein Thioredoxin glutathione reductase Schistosoma mansoni Potency = 39810.7 nM PubChem BioAssay data set
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT2867 Individual protein Protein RecA Mycobacterium tuberculosis IC90 n.a. 40200.0 nM PubChem BioAssay data set
NPT1255 Individual protein Sentrin-specific protease 8 Homo sapiens IC50 > 5000.0 nM PubChem BioAssay data set
NPT1255 Individual protein Sentrin-specific protease 8 Homo sapiens IC50 = 5470.0 nM PubChem BioAssay data set
NPT1256 Individual protein Sentrin-specific protease 7 Homo sapiens IC50 = 4630.0 nM PubChem BioAssay data set
NPT1257 Individual protein Sentrin-specific protease 6 Homo sapiens IC50 = 1860.0 nM PubChem BioAssay data set
NPT2866 Individual protein Replicative DNA helicase Mycobacterium tuberculosis AC50 = 549.7 nM PubChem BioAssay data set
NPT2867 Individual protein Protein RecA Mycobacterium tuberculosis EC50 = 614.0 nM PubChem BioAssay data set
NPT2866 Individual protein Replicative DNA helicase Mycobacterium tuberculosis AC50 = 10340.0 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 1032.3 nM PubChem BioAssay data set
NPT1274 Individual protein DNA repair protein RAD52 homolog Homo sapiens AC50 = 2140.0 nM PubChem BioAssay data set
NPT105 Individual protein Muscleblind-like protein 1 Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 177.4 nM PubChem BioAssay data set
NPT4907 Individual protein Tyrosyl-DNA phosphodiesterase 2 Homo sapiens IC50 = 4598.0 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT791 Individual protein Cruzipain Trypanosoma cruzi Potency = 39810.7 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT979 Individual protein Caspase-3 Homo sapiens IC50 = 907.0 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 8912.5 nM PubChem BioAssay data set
NPT446 Individual protein Rap guanine nucleotide exchange factor 3 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT20556 Single protein Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = 15.75 % DOI[10.6019/CHEMBL4495564]
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 14125.4 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT56 Individual protein Beta-lactamase AmpC Escherichia coli K-12 Potency = 50118.7 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 8199.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 11689.1 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 4147.5 nM PubChem BioAssay data set
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = -0.09 % DOI[10.6019/CHEMBL4495565]
NPT2 Others Unspecified n.a. Potency = 16360.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 > 114670.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. CC50 > 40000.0 nM PubChem BioAssay data set

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference
- Mus musculus LD50 = 3.305270095 mg/kg TOXRIC

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC325871 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC99659
0.8182 Intermediate Similarity NPC63997
0.8182 Intermediate Similarity NPC16805
0.8182 Intermediate Similarity NPC167546
0.7368 Intermediate Similarity NPC136508
0.7143 Intermediate Similarity NPC326316
0.7143 Intermediate Similarity NPC81733
0.7069 Intermediate Similarity NPC253043
0.678 Remote Similarity NPC239775
0.6618 Remote Similarity NPC606311
0.619 Remote Similarity NPC266753
0.619 Remote Similarity NPC160298
0.6154 Remote Similarity NPC229166
0.6129 Remote Similarity NPC205421
0.6129 Remote Similarity NPC474931
0.6129 Remote Similarity NPC607722
0.5938 Remote Similarity NPC19520
0.5909 Remote Similarity NPC128560
0.5873 Remote Similarity NPC247389
0.5846 Remote Similarity NPC199465
0.5625 Remote Similarity NPC306902
0.5625 Remote Similarity NPC232924
0.5616 Remote Similarity NPC112248
0.5484 Remote Similarity NPC13504
0.5469 Remote Similarity NPC117188
0.5469 Remote Similarity NPC145832
0.5455 Remote Similarity NPC219341
0.5455 Remote Similarity NPC476432
0.5455 Remote Similarity NPC24264
0.5325 Remote Similarity NPC47077
0.5323 Remote Similarity NPC470925
0.5312 Remote Similarity NPC212794
0.5312 Remote Similarity NPC606254
0.5294 Remote Similarity NPC298979
0.5294 Remote Similarity NPC320223
0.5294 Remote Similarity NPC600118
0.5294 Remote Similarity NPC610764
0.5231 Remote Similarity NPC600388
0.5224 Remote Similarity NPC226102
0.5143 Remote Similarity NPC114364

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC325871 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data