Natural Product: NPC170503

Natural Product IDNPC170503
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-1,2-Dimethoxy-5,6,6A,7-Tetrahydro-4H-Dibenzo[De,G]Quinoline
IUPAC Name (6aS)-1,2-dimethoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL325416
PubChem CID 41169
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 QQKAHDMMPBQDAC-AWEZNQCLSA-N
Standard InCHI InChI=1S/C18H19NO2/c1-20-15-10-12-7-8-19-14-9-11-5-3-4-6-13(11)17(16(12)14)18(15)21-2/h3-6,10,14,19H,7-9H2,1-2H3/t14-/m0/s1
SMILES COc1cc2CCN[C@H]3Cc4ccccc4-c(c23)c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   281.14 Volume:   298.417
?
Van der Waals volume.
Dense:   0.942 LogP:   2.578
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.5
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.122
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   20.0
TPSA:   30.49
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.917 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.868 Fsp3:   0.333
MCE-18:   66.667
?
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:   0.573 Fluc inhibitor:   0.462
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.585
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.438
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.507

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.89 MDCK Permeability:   -4.831
Pgp-inhibitor:   0.109 Pgp-substrate:   0.973
PAMPA:   0.073
?
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):   0.015
20% Bioavailability (F20%):   0.487 30% Bioavailability (F30%):   0.674
50% Bioavailability (F50%):   0.89

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.413 MRP1:   0.967
Plasma Protein Binding (PPB):   83.541% Volume Distribution (VD):   0.466
Fu: 15.952%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.634
OATP1B3 inhibitor:   0.812 BCRP inhibitor:   0.144
BSEP inhibitor:   0.938

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.031
CYP2C19-inhibitor:   0.995 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.692 CYP2C9-substrate:   0.723
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.261
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.969
CYP2B6-substrate:   0.583 CYP2C8-inhibitor:   0.003
HLM stability:   0.512
?
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):  7.288 Half-life (T1/2):  2.318

ADMET: Toxicity

hERG Blockers:  0.508 hERG Blockers (10um):  0.724
Human Hepatotoxicity (H-HT):  0.69 Drug-induced Liver Injury (DILI):  0.195
AMES Toxicity:  0.779 Rat Oral Acute Toxicity:  0.828
Maximum Recommended Daily Dose:  0.902 Skin Sensitization:  0.814
Carcinogencity:  0.468 Eye Corrosion:  0.009
Eye Irritation:  0.389 Respiratory Toxicity:  0.982
Drug-induced Neurotoxicity:  0.925 Ototoxicity:  0.321
Hematotoxicity:  0.164 Drug-induced Nephrotoxicity:  0.57
Genotoxicity:  0.783 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.366 Hek293 Cytotoxicity:  0.239
BCF:   2.148
?
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:   3.99
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.163
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.62
?
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
NPO6257 Ficus septica Species Moraceae Eukaryota Stems Tainan Hsien, Taiwan, Republic of China 2000-JAN PMID[16038551]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[1659613]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota stem bark n.a. n.a. PMID[17918910]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. stem n.a. PMID[18175990]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota Stems; Barks n.a. n.a. PMID[19086868]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. PMID[19919095]
NPO6257 Ficus septica Species Moraceae Eukaryota leaves n.a. n.a. PMID[19938815]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota flower buds and leaves Khon Kaen province, Thailand 2010 PMID[23270663]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Leaves n.a. n.a. PMID[23642481]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. root n.a. PMID[23738470]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[23738470]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. bark n.a. PMID[23823874]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[25275213]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Flowers n.a. n.a. PMID[26462418]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[28485933]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13118 Paeonia officinalis Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6257 Ficus septica Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11817 Seiridium cardinale Species Sporocadaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO794 Lippia graveolens Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7346 Ligularia odontomanes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1187 Baccharis scandens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11706 Gordonia terrae Species Gordoniaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO794 Lippia graveolens Species Verbenaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO794 Lippia graveolens Species Verbenaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO794 Lippia graveolens Species Verbenaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO13118 Paeonia officinalis Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6257 Ficus septica Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13097 Guatteria amplifolia Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13118 Paeonia officinalis Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6257 Ficus septica Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO794 Lippia graveolens Species Verbenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12193 Metadina trichotoma Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7346 Ligularia odontomanes Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11948 Ferulago sylvatica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12080 Metrodorea flavida Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10161 Macaranga pleiostemona Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13118 Paeonia officinalis Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11817 Seiridium cardinale Species Sporocadaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3478 Nelumbo nucifera Species Nelumbonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11791 Magnolia obovata Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8078 Palaquium leiocarpum Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1187 Baccharis scandens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3390 Radermachia sinica n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO11706 Gordonia terrae Species Gordoniaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO1863 Alpinia pricei Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6257 Ficus septica Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO474 Beilschmiedia kunstleri Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20070.1 Crinum stuhlmannii subsp. delagoense Subspecies Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15978 Nalanthamala diospyri Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4368 Magnolia officinalis Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12316 Pterospermum lanceolatum Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13097 Guatteria amplifolia Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2618 Curcuma wenyujin Species Zingiberaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus Aggregation = 77.1 % PMID[10612588]
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus Aggregation = 0.0 % PMID[10612588]
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus Aggregation = 30.6 % PMID[10612588]
NPT419 Organism Oryctolagus cuniculus Oryctolagus cuniculus IC50 = 210600.0 nM PMID[10612588]

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

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 NPC170503 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 NPC203784
1.0 High Similarity NPC126519
0.7818 Intermediate Similarity NPC189470
0.7818 Intermediate Similarity NPC191213
0.6897 Remote Similarity NPC302713
0.6724 Remote Similarity NPC81247
0.6724 Remote Similarity NPC35627
0.6724 Remote Similarity NPC299687
0.6724 Remote Similarity NPC476573
0.6571 Remote Similarity NPC475754
0.6552 Remote Similarity NPC298008
0.6441 Remote Similarity NPC69712
0.6441 Remote Similarity NPC148709
0.6441 Remote Similarity NPC220228
0.6129 Remote Similarity NPC112575
0.6066 Remote Similarity NPC192135
0.5806 Remote Similarity NPC6152
0.5538 Remote Similarity NPC152212
0.5538 Remote Similarity NPC28341
0.5397 Remote Similarity NPC173416
0.5373 Remote Similarity NPC155442
0.5373 Remote Similarity NPC312918
0.5312 Remote Similarity NPC608930
0.5231 Remote Similarity NPC470879
0.5224 Remote Similarity NPC267408
0.5072 Remote Similarity NPC135772

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC170503 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