Natural Product: NPC99233

Natural Product IDNPC99233
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Mahkoside A
IUPAC Name [2-hydroxy-4-methoxy-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]-(4-hydroxyphenyl)methanone
Synonyms Mahkoside A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2159665
PubChem CID 71451475
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic glycosides

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 LCZPALDWQFYTCU-LWUBGYQZSA-N
Standard InCHI InChI=1S/C20H22O10/c1-28-11-6-12(23)15(16(24)9-2-4-10(22)5-3-9)13(7-11)29-20-19(27)18(26)17(25)14(8-21)30-20/h2-7,14,17-23,25-27H,8H2,1H3/t14-,17-,18+,19-,20-/m1/s1
SMILES COc1cc(c(c(c1)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)C(=O)c1ccc(cc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.12 Volume:   398.254
?
Van der Waals volume.
Dense:   1.06 LogP:   0.891
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.392
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.471
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   166.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.335 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.671 Fsp3:   0.35
MCE-18:   70.778
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.384 Fluc inhibitor:   0.195
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.135
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.605
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.199 Promiscuous compounds:   0.506

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.15 MDCK Permeability:   -5.036
Pgp-inhibitor:   0.003 Pgp-substrate:   0.092
PAMPA:   0.846
?
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):   0.257
20% Bioavailability (F20%):   0.068 30% Bioavailability (F30%):   0.939
50% Bioavailability (F50%):   0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.035
Plasma Protein Binding (PPB):   84.787% Volume Distribution (VD):   0.02
Fu: 15.52%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.561
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.119 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.007 CYP2D6-substrate:   0.037
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.228
HLM stability:   0.169
?
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):  3.123 Half-life (T1/2):  3.069

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.14
Human Hepatotoxicity (H-HT):  0.716 Drug-induced Liver Injury (DILI):  0.872
AMES Toxicity:  0.874 Rat Oral Acute Toxicity:  0.025
Maximum Recommended Daily Dose:  0.066 Skin Sensitization:  0.991
Carcinogencity:  0.211 Eye Corrosion:  0.0
Eye Irritation:  0.422 Respiratory Toxicity:  0.063
Drug-induced Neurotoxicity:  0.035 Ototoxicity:  0.916
Hematotoxicity:  0.297 Drug-induced Nephrotoxicity:  0.729
Genotoxicity:  0.545 RPMI-8226 Immunitoxicity:  0.109
A549 Cytotoxicity:  0.437 Hek293 Cytotoxicity:  0.455
BCF:   0.517
?
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:   3.249
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.648
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.824
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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
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. DOI[10.1246/bcsj.30.618]
NPO25054 Phaleria macrocarpa Species Thymelaeaceae Eukaryota nut shell n.a. n.a. PMID[23044367]
NPO33051 mango tree n.a. n.a. n.a. stem bark n.a. n.a. PMID[24613627]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. PMID[27466882]
NPO25054 Phaleria macrocarpa Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25054 Phaleria macrocarpa 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
NPT3084 Individual protein Neuraminidase Influenza A virus Inhibition = 8.1 % PMID[26000707]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT306 Cell line PC-3 Homo sapiens IC50 > 100000.0 nM PMID[19902967]
NPT3140 Cell line MGC-803 Homo sapiens IC50 > 100000.0 nM PMID[17910513]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[23044367]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. PC50 > 100.0 uM PMID[27466882]

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 NPC99233 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
0.75 Intermediate Similarity NPC604892
0.7391 Intermediate Similarity NPC43638
0.7164 Intermediate Similarity NPC606849
0.6761 Remote Similarity NPC106625
0.6508 Remote Similarity NPC23084
0.6164 Remote Similarity NPC39351
0.6081 Remote Similarity NPC206378
0.6027 Remote Similarity NPC308265
0.6 Remote Similarity NPC600107
0.5921 Remote Similarity NPC300537
0.5921 Remote Similarity NPC472320
0.5846 Remote Similarity NPC218685
0.5775 Remote Similarity NPC121001
0.5733 Remote Similarity NPC219163
0.5667 Remote Similarity NPC142319
0.5645 Remote Similarity NPC152722
0.5616 Remote Similarity NPC57587
0.5574 Remote Similarity NPC217854
0.5541 Remote Similarity NPC30432
0.5538 Remote Similarity NPC214454
0.5507 Remote Similarity NPC222455
0.5467 Remote Similarity NPC169248
0.5467 Remote Similarity NPC271479
0.5467 Remote Similarity NPC72649
0.5441 Remote Similarity NPC214910
0.541 Remote Similarity NPC276195
0.5405 Remote Similarity NPC177742
0.5395 Remote Similarity NPC97052
0.5395 Remote Similarity NPC259182
0.5395 Remote Similarity NPC88484
0.5395 Remote Similarity NPC76128
0.5395 Remote Similarity NPC163191
0.5385 Remote Similarity NPC221090
0.5385 Remote Similarity NPC145900
0.5375 Remote Similarity NPC236934
0.5333 Remote Similarity NPC148273
0.5333 Remote Similarity NPC601828
0.5333 Remote Similarity NPC605700
0.5325 Remote Similarity NPC471457
0.5325 Remote Similarity NPC486379
0.5286 Remote Similarity NPC106025
0.5263 Remote Similarity NPC604833
0.5256 Remote Similarity NPC149244
0.5238 Remote Similarity NPC153149
0.5238 Remote Similarity NPC192810
0.5224 Remote Similarity NPC40377
0.5211 Remote Similarity NPC85799
0.5211 Remote Similarity NPC303422
0.5195 Remote Similarity NPC170475
0.519 Remote Similarity NPC29830
0.5156 Remote Similarity NPC25817
0.5139 Remote Similarity NPC199335
0.5139 Remote Similarity NPC477240
0.5128 Remote Similarity NPC61594
0.5068 Remote Similarity NPC294166
0.5068 Remote Similarity NPC190217
0.5068 Remote Similarity NPC115022
0.5067 Remote Similarity NPC210192
0.5063 Remote Similarity NPC6985
0.5063 Remote Similarity NPC472353

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC99233 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