Natural Product: NPC262039

Natural Product IDNPC262039
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bonanniol A
IUPAC Name (2R,3R)-6-[(2E)-3,7-dimethylocta-2,6-dienyl]-3,5,7-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL220418
PubChem CID 21721861
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-prenylated flavanones

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 WCWOWFQELCQQCI-AUSBBASTSA-N
Standard InCHI InChI=1S/C25H28O6/c1-14(2)5-4-6-15(3)7-12-18-19(27)13-20-21(22(18)28)23(29)24(30)25(31-20)16-8-10-17(26)11-9-16/h5,7-11,13,24-28,30H,4,6,12H2,1-3H3/b15-7+/t24-,25+/m0/s1
SMILES CC(=CCC/C(=C/Cc1c(cc2c(c1O)C(=O)[C@@H]([C@@H](c1ccc(cc1)O)O2)O)O)/C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.19 Volume:   444.3
?
Van der Waals volume.
Dense:   0.955 LogP:   4.676
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.519
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.885
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   20.0
TPSA:   107.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.5 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.72 Fsp3:   0.32
MCE-18:   65.545
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.911 Fluc inhibitor:   0.374
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.563
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.65
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.191 Promiscuous compounds:   0.098

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.324 MDCK Permeability:   -4.914
Pgp-inhibitor:   0.998 Pgp-substrate:   0.015
PAMPA:   0.058
?
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):   0.002
20% Bioavailability (F20%):   0.025 30% Bioavailability (F30%):   0.931
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.753
Plasma Protein Binding (PPB):   95.637% Volume Distribution (VD):   0.241
Fu: 4.319%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.641
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.061
CYP2C19-inhibitor:   0.922 CYP2C19-substrate:   0.225
CYP2C9-inhibitor:   0.979 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.954 CYP2D6-substrate:   0.976
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.984
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.977
HLM stability:   0.964
?
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):  6.147 Half-life (T1/2):  1.531

ADMET: Toxicity

hERG Blockers:  0.076 hERG Blockers (10um):  0.552
Human Hepatotoxicity (H-HT):  0.955 Drug-induced Liver Injury (DILI):  0.742
AMES Toxicity:  0.329 Rat Oral Acute Toxicity:  0.721
Maximum Recommended Daily Dose:  0.408 Skin Sensitization:  0.999
Carcinogencity:  0.222 Eye Corrosion:  0.0
Eye Irritation:  0.882 Respiratory Toxicity:  0.821
Drug-induced Neurotoxicity:  0.582 Ototoxicity:  0.536
Hematotoxicity:  0.333 Drug-induced Nephrotoxicity:  0.931
Genotoxicity:  0.968 RPMI-8226 Immunitoxicity:  0.318
A549 Cytotoxicity:  0.925 Hek293 Cytotoxicity:  0.804
BCF:   2.028
?
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:   5.035
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.602
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.009
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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
NPO27255 Macaranga alnifolia Species Euphorbiaceae Eukaryota n.a. leaf n.a. DOI[10.1016/0031-9422(92)80315-6]
NPO32704 monotes africanus Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. PMID[11325248]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. Madagascar rainforest n.a. PMID[15787448]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. fruit n.a. PMID[15787448]
NPO27255 Macaranga alnifolia Species Euphorbiaceae Eukaryota n.a. Madagascar rainforest n.a. PMID[17326683]
NPO27255 Macaranga alnifolia Species Euphorbiaceae Eukaryota n.a. fruit n.a. PMID[17326683]
NPO27255 Macaranga alnifolia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27255 Macaranga alnifolia Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16269 Schizolaena hystrix Species Sarcolaenaceae 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
NPT571 Cell line A2780cisR Homo sapiens IC50 = 23500.0 nM PMID[17923492]
NPT179 Cell line A2780 Homo sapiens IC50 = 25.0 ug.mL-1 PMID[21182258]

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 NPC262039 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
0.8636 High Similarity NPC22192
0.8028 Intermediate Similarity NPC287328
0.7746 Intermediate Similarity NPC282009
0.7714 Intermediate Similarity NPC470326
0.7143 Intermediate Similarity NPC228504
0.6538 Remote Similarity NPC471499
0.6389 Remote Similarity NPC477242
0.6351 Remote Similarity NPC213896
0.6184 Remote Similarity NPC185276
0.6 Remote Similarity NPC290133
0.5974 Remote Similarity NPC472627
0.5949 Remote Similarity NPC195796
0.5921 Remote Similarity NPC64915
0.5915 Remote Similarity NPC254412
0.5844 Remote Similarity NPC470328
0.5844 Remote Similarity NPC488556
0.5844 Remote Similarity NPC209614
0.5823 Remote Similarity NPC472628
0.5789 Remote Similarity NPC488440
0.5714 Remote Similarity NPC472629
0.5696 Remote Similarity NPC226025
0.5696 Remote Similarity NPC278778
0.5696 Remote Similarity NPC298692
0.5641 Remote Similarity NPC164272
0.5641 Remote Similarity NPC470327
0.557 Remote Similarity NPC58805
0.5556 Remote Similarity NPC210459
0.5493 Remote Similarity NPC20907
0.5373 Remote Similarity NPC62290
0.5373 Remote Similarity NPC142731
0.5373 Remote Similarity NPC326506
0.5366 Remote Similarity NPC45849
0.5366 Remote Similarity NPC472626
0.5342 Remote Similarity NPC266689
0.5342 Remote Similarity NPC262038
0.5342 Remote Similarity NPC319910
0.5309 Remote Similarity NPC321779
0.527 Remote Similarity NPC23126
0.5233 Remote Similarity NPC321399
0.5185 Remote Similarity NPC261063
0.5135 Remote Similarity NPC483966
0.5135 Remote Similarity NPC171651
0.5072 Remote Similarity NPC201837
0.507 Remote Similarity NPC611035
0.5068 Remote Similarity NPC249606
0.5067 Remote Similarity NPC35567
0.5063 Remote Similarity NPC166934

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC262039 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