Natural Product: NPC253043

Natural Product IDNPC253043
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Predicentrine
IUPAC Name (6aS)-1,9,10-trimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2-ol
Synonyms (+)-Predicentrine; Predicentrine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL404136
PubChem CID 10042942
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 OUTYMWDDJORZOH-AWEZNQCLSA-N
Standard InCHI InChI=1S/C20H23NO4/c1-21-6-5-11-8-15(22)20(25-4)19-13-10-17(24-3)16(23-2)9-12(13)7-14(21)18(11)19/h8-10,14,22H,5-7H2,1-4H3/t14-/m0/s1
SMILES COc1cc2c(cc1OC)C[C@H]1c3c2c(OC)c(O)cc3CCN1C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   341.16 Volume:   350.589
?
Van der Waals volume.
Dense:   0.973 LogP:   1.991
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.238
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.731
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   20.0
TPSA:   51.16
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.929 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.051 Fsp3:   0.4
MCE-18:   75.571
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.602 Fluc inhibitor:   0.045
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.608
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.348
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.004 Promiscuous compounds:   0.786

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.917 MDCK Permeability:   -4.734
Pgp-inhibitor:   0.037 Pgp-substrate:   0.875
PAMPA:   0.01
?
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):   0.036
20% Bioavailability (F20%):   0.847 30% Bioavailability (F30%):   0.89
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.369 MRP1:   0.952
Plasma Protein Binding (PPB):   62.285% Volume Distribution (VD):   0.122
Fu: 36.975%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.963
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.86
BSEP inhibitor:   0.723

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.909 CYP2C9-substrate:   0.013
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.007
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.317
CYP2B6-substrate:   0.999 CYP2C8-inhibitor:   0.112
HLM stability:   0.306
?
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):  9.33 Half-life (T1/2):  2.439

ADMET: Toxicity

hERG Blockers:  0.391 hERG Blockers (10um):  0.703
Human Hepatotoxicity (H-HT):  0.53 Drug-induced Liver Injury (DILI):  0.037
AMES Toxicity:  0.618 Rat Oral Acute Toxicity:  0.735
Maximum Recommended Daily Dose:  0.926 Skin Sensitization:  0.662
Carcinogencity:  0.668 Eye Corrosion:  0.001
Eye Irritation:  0.121 Respiratory Toxicity:  0.956
Drug-induced Neurotoxicity:  0.835 Ototoxicity:  0.333
Hematotoxicity:  0.14 Drug-induced Nephrotoxicity:  0.295
Genotoxicity:  0.816 RPMI-8226 Immunitoxicity:  0.088
A549 Cytotoxicity:  0.285 Hek293 Cytotoxicity:  0.355
BCF:   1.655
?
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:   4.004
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.419
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.532
?
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
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[11141125]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. PMID[11421751]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[12398544]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. PMID[12762811]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[18419154]
NPO32522 desmos rostrata Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[19053513]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[19296389]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[21910504]
NPO2884 Annona squamosa Species Annonaceae Eukaryota seeds n.a. n.a. PMID[22011319]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. seed n.a. PMID[22011319]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Barks n.a. n.a. PMID[2348205]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. fruit n.a. PMID[8786370]
NPO2884 Annona squamosa Species Annonaceae Eukaryota bark n.a. n.a. PMID[9214729]
NPO11053 Annona purpurea Species Annonaceae Eukaryota seeds n.a. n.a. PMID[9599253]
NPO32857 cassytha filiformis ii Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[9677264]
NPO11053 Annona purpurea Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[9868142]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11053 Annona purpurea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2533 Cardamine amara Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2099 Asteronyx loveni Species Asteronychidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11053 Annona purpurea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11053 Annona purpurea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO11053 Annona purpurea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2533 Cardamine amara Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11053 Annona purpurea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2099 Asteronyx loveni Species Asteronychidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO478 Mazzaella laminarioides Species Gigartinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6146 Stereocaulon sterile Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2884 Annona squamosa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO5394 Litsea sericea Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8039 Wikstroemia hainanensis Species Thymelaeaceae 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
NPT1857 Individual protein Dopamine D1 receptor Rattus norvegicus Ki = 240.0 nM PMID[17228858]
NPT1858 Individual protein Dopamine D2 receptor Rattus norvegicus Ki = 760.0 nM PMID[17228858]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens IC50 > 29000.0 nM PMID[19053513]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 27800.0 nM PMID[19053513]
NPT20967 Cell line Platelet n.a. Activity = 0.0 % PMID[9677264]
NPT20967 Cell line Platelet n.a. Activity = 74.0 % PMID[9677264]
NPT20967 Cell line Platelet n.a. Activity = 88.9 % PMID[9868142]
NPT20967 Cell line Platelet n.a. Activity = 62.0 % PMID[9868142]
NPT20967 Cell line Platelet n.a. Activity = 83.2 % PMID[9868142]

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 NPC253043 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
0.8036 Intermediate Similarity NPC13504
0.7069 Intermediate Similarity NPC99659
0.7069 Intermediate Similarity NPC325871
0.7049 Intermediate Similarity NPC195075
0.7049 Intermediate Similarity NPC27410
0.6774 Remote Similarity NPC136508
0.6774 Remote Similarity NPC600388
0.6508 Remote Similarity NPC239775
0.6406 Remote Similarity NPC63997
0.6406 Remote Similarity NPC16805
0.6406 Remote Similarity NPC167546
0.6176 Remote Similarity NPC229166
0.6119 Remote Similarity NPC199465
0.6094 Remote Similarity NPC212794
0.5846 Remote Similarity NPC606254
0.5846 Remote Similarity NPC609009
0.5714 Remote Similarity NPC128560
0.5571 Remote Similarity NPC320223
0.5441 Remote Similarity NPC205421
0.5441 Remote Similarity NPC474931
0.5441 Remote Similarity NPC607722
0.5303 Remote Similarity NPC158376
0.5294 Remote Similarity NPC117188
0.5294 Remote Similarity NPC145832
0.5152 Remote Similarity NPC135538
0.5152 Remote Similarity NPC24233
0.5139 Remote Similarity NPC600118
0.5075 Remote Similarity NPC326316
0.5075 Remote Similarity NPC81733
0.5072 Remote Similarity NPC605949

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC253043 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