ID: ALA419335

Max Phase: Preclinical

Molecular Formula: C14H15NO8

Molecular Weight: 325.27

Molecule Type: Small molecule

Representations

Synonyms (2): (+)-Pancratistatin | Pancratistatin
Synonyms from Alternative Forms(2):

Canonical SMILES:  O=C1N[C@H]2[C@H](O)[C@H](O)[C@@H](O)[C@H](O)[C@@H]2c2cc3c(c(O)c21)OCO3

Standard InChI:  InChI=1S/C14H15NO8/c16-8-5-3-1-4-13(23-2-22-4)9(17)6(3)14(21)15-7(5)10(18)12(20)11(8)19/h1,5,7-8,10-12,16-20H,2H2,(H,15,21)/t5-,7-,8-,10+,11+,12+/m1/s1

Standard InChI Key:  VREZDOWOLGNDPW-ALTGWBOUSA-N

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 325.27

Molecular Weight (Monoisotopic): 325.0798

AlogP: -2.23

#Rotatable Bonds: 0

Polar Surface Area: 148.71

Molecular Species: NEUTRAL

HBA: 8

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 9

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 8.48

CX Basic pKa:

CX LogP: -1.92

CX LogD: -1.95

Aromatic Rings: 1

Heavy Atoms: 23

QED Weighted: 0.31

Np Likeness Score: 2.03

References

1. Rinner U, Hillebrenner HL, Adams DR, Hudlicky T, Pettit GR..  (2004)  Synthesis and biological activity of some structural modifications of pancratistatin.,  14  (11): [PMID:15125958] [10.1016/j.bmcl.2004.03.032]

2. McNulty J, Larichev V, Pandey S..  (2005)  A synthesis of 3-deoxydihydrolycoricidine: refinement of a structurally minimum pancratistatin pharmacophore.,  15  (23): [PMID:16183280] [10.1016/j.bmcl.2005.08.024]

3. Pettit GR, Melody N, Herald DL, Knight JC, Chapuis JC..  (2007)  Antineoplastic agents. 550. Synthesis of 10b(s)-epipancratistatin from (+)-narciclasine.,  70  (3): [PMID:17346078] [10.1021/np068046e]

4. McNulty J, Nair JJ, Griffin C, Pandey S..  (2008)  synthesis and biological evaluation of fully functionalized seco-pancratistatin analogues.,  71  (3): [PMID:18225861] [10.1021/np0705460]

5. Pettit GR, Meng Y, Herald DL, Knight JC, Day JF..  (2005)  Antineoplastic agents. 553. The Texas grasshopper Brachystola magna.,  68  (8): [PMID:16124772] [10.1021/np0402367]

6. Pettit GR, Gaddamidi V, Herald DL, Singh SB, Cragg GM, Schmidt JM, Boettner FE, Williams M, Sagawa Y..  (1986)  Antineoplastic agents, 120. Pancratium littorale.,  49  (6): [PMID:3572427] [10.1021/np50048a005]

7. Pettit GR, Eastham SA, Melody N, Orr B, Herald DL, McGregor J, Knight JC, Doubek DL, Pettit GR, Garner LC, Bell JA..  (2006)  Isolation and structural modification of 7-deoxynarciclasine and 7-deoxy-trans-dihydronarciclasine.,  69  (1): [PMID:16441059] [10.1021/np058068l]

8. Pettit GR, Melody N, Herald DL..  (2004)  Antineoplastic agents. 511. Direct phosphorylation of phenpanstatin and pancratistatin.,  67  (3): [PMID:15043403] [10.1021/np030299+]

9. Pettit GR, Pettit GR, Backhaus RA, Boettner FE..  (1995)  Antineoplastic agents, 294. Variations in the formation of pancratistatin and related isocarbostyrils in Hymenocallis littoralis.,  58  (1): [PMID:7760076] [10.1021/np50115a004]

10. Pettit GR, Gaddamidi V, Cragg GM..  (1984)  Antineoplastic agents, 105. Zephyranthes grandiflora.,  47  (6): [PMID:6549467] [10.1021/np50036a020]

11. Pettit GR, Pettit GR, Backhaus RA, Boyd MR, Meerow AW..  (1993)  Antineoplastic agents, 256. Cell growth inhibitory isocarbostyrils from Hymenocallis.,  56  (10): [PMID:8277308] [10.1021/np50100a004]

12. Gabrielsen B, Monath TP, Huggins JW, Kefauver DF, Pettit GR, Groszek G, Hollingshead M, Kirsi JJ, Shannon WM, Schubert EM..  (1992)  Antiviral (RNA) activity of selected Amaryllidaceae isoquinoline constituents and synthesis of related substances.,  55  (11): [PMID:1336040] [10.1021/np50089a003]

13. McNulty J, Nair JJ, Singh M, Crankshaw DJ, Holloway AC, Bastida J..  (2009)  Selective cytochrome P450 3A4 inhibitory activity of Amaryllidaceae alkaloids.,  19  (12): [PMID:19428250] [10.1016/j.bmcl.2009.04.086]

14. PubChem BioAssay data set, 

15. Pettit GR, Tan R, Bao GH, Melody N, Doubek DL, Gao S, Chapuis JC, Williams L..  (2012)  Antineoplastic agents. 587. Isolation and structure of 3-epipancratistatin from Narcissus cv. Ice Follies.,  75  (4): [PMID:22413911] [10.1021/np200862y]

16. Nair JJ, Rárová L, Strnad M, Bastida J, van Staden J..  (2012)  Apoptosis-inducing effects of distichamine and narciprimine, rare alkaloids of the plant family Amaryllidaceae.,  22  (19): [PMID:22921081] [10.1016/j.bmcl.2012.08.005]

17. McNulty J, D'Aiuto L, Zhi Y, McClain L, Zepeda-Velázquez C, Ler S, Jenkins HA, Yee MB, Piazza P, Yolken RH, Kinchington PR, Nimgaonkar VL..  (2016)  iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections.,  7  (1): [PMID:26819664] [10.1021/acsmedchemlett.5b00318]

18. Johannes Zuegg, Alysha Elliott, Maite Amado, Emma Cowie, Ali Hinton, Geraldine Kaeslin, Angela Kavanagh, Anne Kunert, Gabriell Lowe, Soumya Ramu, Janet Reid, Robin Trauer, Mathilde Desselle, Ruth Neale, Karl Hansford, Mark Blascovich, Matthew Cooper. CO-ADD screening of NIH NCI Diversity Set V,  [10.6019/CHEMBL4296182]

Source

Source(3):

• Scientific Literature
• PubChem BioAssays
• CO-ADD antimicrobial screening data