Natural Product: NPC305542

Natural Product IDNPC305542
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-Hydroxynoracronycine
IUPAC Name 6,11-dihydroxy-3,3,12-trimethylpyrano[2,3-c]acridin-7-one
Synonyms 5-Hydroxynoracronycine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL447169
PubChem CID 5378702
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0001908] Benzoquinolines
          • [CHEMONTID:0000274] Acridines
            • [CHEMONTID:0001811] Acridones

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 JZQDCDLYNFZBIG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H17NO4/c1-19(2)8-7-10-14(24-19)9-13(22)15-17(10)20(3)16-11(18(15)23)5-4-6-12(16)21/h4-9,21-22H,1-3H3
SMILES CC1(C)C=Cc2c(cc(c3c2n(C)c2c(cccc2O)c3=O)O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   323.12 Volume:   328.02
?
Van der Waals volume.
Dense:   0.985 LogP:   3.358
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.0
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.784
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   71.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.623 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.019 Fsp3:   0.211
MCE-18:   52.174
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.494 Fluc inhibitor:   0.274
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.629
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.601
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.023 Promiscuous compounds:   0.207

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.914 MDCK Permeability:   -4.689
Pgp-inhibitor:   0.078 Pgp-substrate:   0.055
PAMPA:   0.712
?
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%):   0.217 30% Bioavailability (F30%):   0.699
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.061 MRP1:   0.984
Plasma Protein Binding (PPB):   96.36% Volume Distribution (VD):   0.318
Fu: 3.288%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.11
BSEP inhibitor:   0.888

ADMET: Metabolism

CYP1A2-inhibitor:   0.96 CYP1A2-substrate:   0.921
CYP2C19-inhibitor:   0.1 CYP2C19-substrate:   0.008
CYP2C9-inhibitor:   0.456 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   0.036
CYP3A4-inhibitor:   0.455 CYP3A4-substrate:   0.335
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.917
HLM stability:   0.927
?
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):  1.962 Half-life (T1/2):  1.508

ADMET: Toxicity

hERG Blockers:  0.189 hERG Blockers (10um):  0.563
Human Hepatotoxicity (H-HT):  0.756 Drug-induced Liver Injury (DILI):  0.871
AMES Toxicity:  0.874 Rat Oral Acute Toxicity:  0.588
Maximum Recommended Daily Dose:  0.616 Skin Sensitization:  0.874
Carcinogencity:  0.829 Eye Corrosion:  0.0
Eye Irritation:  0.604 Respiratory Toxicity:  0.966
Drug-induced Neurotoxicity:  0.798 Ototoxicity:  0.643
Hematotoxicity:  0.585 Drug-induced Nephrotoxicity:  0.727
Genotoxicity:  0.608 RPMI-8226 Immunitoxicity:  0.201
A549 Cytotoxicity:  0.417 Hek293 Cytotoxicity:  0.54
BCF:   1.66
?
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:   4.42
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.881
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.255
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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
NPO25903 Swinglea glutinosa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[11575960]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota Root Bark n.a. n.a. PMID[21985060]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. root n.a. PMID[21985060]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25903 Swinglea glutinosa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5476 Hortia arborea Species Rutaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO7221 Korolkowia sewerzowi n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO2786 Clematis flammula Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5476 Hortia arborea Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1762 Citropsis articulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25903 Swinglea glutinosa Species Rutaceae 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
NPT601 Individual protein Cathepsin L2 Homo sapiens IC50 = 48000.0 nM PMID[21277783]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens ED50 = 85.5 uM PMID[11575960]
NPT165 Cell line HeLa Homo sapiens ED50 = 78.0 uM PMID[11575960]
NPT1353 Cell line CCRF-HSB-2 Homo sapiens IC50 = 23600.0 nM PMID[10217715]
NPT1354 Cell line TGBC11TKB Homo sapiens IC50 = 16200.0 nM PMID[10217715]
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PMID[10217715]
NPT319 Cell line B16 Mus musculus IC50 > 40000.0 nM PMID[10217715]
NPT189 Cell line Vero Chlorocebus aethiops IC50 = 9.3 ug.mL-1 PMID[21985060]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 11100.0 nM PMID[11575960]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 8700.0 nM PMID[11575960]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 10200.0 nM PMID[11575960]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 6800.0 nM PMID[11575960]
NPT1225 Organism Plasmodium falciparum (isolate FcB1 / Columbia) Plasmodium falciparum FcB1/Columbia IC50 = 0.9 ug.mL-1 PMID[21985060]
NPT633 Organism Leishmania donovani Leishmania donovani EC50 = 11.2 ug.mL-1 PMID[21985060]
NPT2 Others Unspecified n.a. Ratio = 7.7 n.a. PMID[11575960]
NPT2 Others Unspecified n.a. Ratio = 9.0 n.a. PMID[11575960]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei EC50 = 125.0 ug.mL-1 PMID[21985060]
NPT2 Others Unspecified n.a. Ratio IC50 = 10.0 n.a. PMID[21985060]

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 NPC305542 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
0.7273 Intermediate Similarity NPC30749
0.6765 Remote Similarity NPC156882
0.6716 Remote Similarity NPC5322
0.6567 Remote Similarity NPC212123
0.6528 Remote Similarity NPC161769
0.5867 Remote Similarity NPC482686
0.5833 Remote Similarity NPC13249
0.5789 Remote Similarity NPC482685
0.5556 Remote Similarity NPC275122
0.5395 Remote Similarity NPC38219
0.5385 Remote Similarity NPC474681
0.5342 Remote Similarity NPC120105
0.5303 Remote Similarity NPC148391
0.5211 Remote Similarity NPC170333
0.5135 Remote Similarity NPC6633

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC305542 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