ID: ALA1159657

Max Phase: Preclinical

Molecular Formula: C36H64O7

Molecular Weight: 608.90

Molecule Type: Small molecule

Representations

Synonyms (2): Bullatacin | Rolliniastatin 2
Synonyms from Alternative Forms(2):

Canonical SMILES:  CCCCCCCCCC[C@@H](O)[C@@H]1CC[C@@H]([C@@H]2CC[C@@H]([C@H](O)CCCCCCCCCC(O)CC3=CC(C)OC3=O)O2)O1

Standard InChI:  InChI=1S/C36H64O7/c1-3-4-5-6-7-10-13-16-19-30(38)32-21-23-34(42-32)35-24-22-33(43-35)31(39)20-17-14-11-8-9-12-15-18-29(37)26-28-25-27(2)41-36(28)40/h25,27,29-35,37-39H,3-24,26H2,1-2H3/t27?,29?,30-,31-,32+,33+,34+,35+/m1/s1

Standard InChI Key:  PJQMINRIJUCTIZ-FKONRUPGSA-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: 608.90

Molecular Weight (Monoisotopic): 608.4652

AlogP: 7.47

#Rotatable Bonds: 24

Polar Surface Area: 105.45

Molecular Species: NEUTRAL

HBA: 7

HBD: 3

#RO5 Violations: 2

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 13.38

CX Basic pKa:

CX LogP: 8.24

CX LogD: 8.24

Aromatic Rings: 0

Heavy Atoms: 43

QED Weighted: 0.08

Np Likeness Score: 1.87

References

1. Rodier S, Le Huérou Y, Renoux B, Doyon J, Renard P, Pierré A, Gesson JP, Grée R..  (2000)  Synthesis and cytotoxic activity of acetogenin analogues.,  10  (12): [PMID:10890167] [10.1016/s0960-894x(00)00236-5]

2. Oberlies NH, Chang CJ, McLaughlin JL..  (1997)  Structure-activity relationships of diverse Annonaceous acetogenins against multidrug resistant human mammary adenocarcinoma (MCF-7/Adr) cells.,  40  (13): [PMID:9207950] [10.1021/jm9700169]

3. Yabunaka H, Abe M, Kenmochi A, Hamada T, Nishioka T, Miyoshi H..  (2003)  Synthesis and inhibitory activity of ubiquinone-acetogenin hybrid inhibitor with bovine mitochondrial complex I.,  13  (14): [PMID:12824040] [10.1016/s0960-894x(03)00439-6]

4. Yao ZJ, Wu HP, Wu YL..  (2000)  Polyether mimics of naturally occurring cytotoxic annonaceous acetogenins.,  43  (12): [PMID:10882377] [10.1021/jm990575a]

5. Nakanishi Y, Chang FR, Liaw CC, Wu YC, Bastow KF, Lee KH..  (2003)  Acetogenins as selective inhibitors of the human ovarian 1A9 tumor cell line.,  46  (15): [PMID:12852747] [10.1021/jm020548b]

6. Gallardo T, Zafra-Polo MC, Tormo JR, González MC, Franck X, Estornell E, Cortes D..  (2000)  Semisynthesis of antitumoral acetogenins: SAR of functionalized alkyl-chain bis-tetrahydrofuranic acetogenins, specific inhibitors of mitochondrial complex I.,  43  (25): [PMID:11123988] [10.1021/jm000911j]

7. Hattori Y, Konno H, Abe M, Miyoshi H, Goto T, Makabe H..  (2007)  Synthesis, determination of the absolute configuration of tonkinelin, and inhibitory action with bovine heart mitochondrial complex I.,  15  (8): [PMID:17321744] [10.1016/j.bmc.2007.02.002]

8. He K, Shi G, Zhao GX, Zeng L, Ye Q, Schwedler JT, Wood KV, McLaughlin JL..  (1996)  Three new adjacent bis-tetrahydrofuran acetogenins with four hydroxyl groups from Asimina triloba.,  59  (11): [PMID:8946743] [10.1021/np9605145]

9. Li XH, Hui YH, Rupprecht JK, Liu YM, Wood KV, Smith DL, Chang CJ, McLaughlin JL..  (1990)  Bullatacin, bullatacinone, and squamone, a new bioactive acetogenin, from the bark of Annona squamosa.,  53  (1): [PMID:2348205] [10.1021/np50067a010]

10. Rupprecht JK, Hui YH, McLaughlin JL..  (1990)  Annonaceous acetogenins: a review.,  53  (2): [PMID:2199608] [10.1021/np50068a001]

11. Rupprecht JK, Hui YH, McLaughlin JL..  (1990)  Annonaceous acetogenins: a review.,  53  (2): [PMID:2199608] [10.1021/np50068a001]

12. McLaughlin JL..  (2008)  Paw paw and cancer: annonaceous acetogenins from discovery to commercial products.,  71  (7): [PMID:18598079] [10.1021/np800191t]

13. Hui YH, Rupprecht JK, Liu YM, Anderson JE, Smith DL, Chang CJ, McLaughlin JL..  (1989)  Bullatacin and bullatacinone: two highly potent bioactive acetogenins from Annona bullata.,  52  (3): [PMID:2778448] [10.1021/np50063a002]

14. Hopp DC, Zeng L, Gu Z, McLaughlin JL..  (1996)  Squamotacin: an annonaceous acetogenin with cytotoxic selectivity for the human prostate tumor cell line (PC-3).,  59  (2): [PMID:8991957] [10.1021/np960124i]

15. Chang FR, Wu YC, Duh CY, Wang SK..  (1993)  Studies on the acetogenins of Formosan annonaceous plants. II. Cytotoxic acetogenins from Annona reticulata.,  56  (10): [PMID:8277309] [10.1021/np50100a005]

16. Chang FR, Wu YC, Duh CY, Wang SK..  (1993)  Studies on the acetogenins of Formosan annonaceous plants. II. Cytotoxic acetogenins from Annona reticulata.,  56  (10): [PMID:8277309] [10.1021/np50100a005]

17. Sinha SC, Chen Z, Huang ZZ, Nakamaru-Ogiso E, Pietraszkiewicz H, Edelstein M, Valeriote F..  (2008)  Alteration of the bis-tetrahydrofuran core stereochemistries in asimicin can affect the cytotoxicity.,  51  (22): [PMID:18975929] [10.1021/jm801028c]

18. Chen Y, Chen JW, Li X..  (2011)  Cytotoxic bistetrahydrofuran annonaceous acetogenins from the seeds of Annona squamosa.,  74  (11): [PMID:22011319] [10.1021/np200708q]

19. Chen Y, Chen JW, Xu SS, Wang Y, Li X, Cai BC, Fan NB..  (2012)  Antitumor activity of annonaceous acetogenins in HepS and S180 xenografts bearing mice.,  22  (8): [PMID:22446092] [10.1016/j.bmcl.2012.02.109]

20. Makabe H, Hattori Y, Kimura Y, Konno H, Abe M, Miyoshi H, Tanaka A, Oritani T.  (2004)  Total synthesis of cis-solamin and its inhibitory action with bovine heart mitochondrial complex I,  60  (47): [10.1016/j.tet.2004.09.011]

21. Shi JF, Wu P, Jiang ZH, Wei XY..  (2014)  Synthesis and tumor cell growth inhibitory activity of biotinylated annonaceous acetogenins.,  71  [PMID:24308999] [10.1016/j.ejmech.2013.11.012]

Source

Source(1):

• Scientific Literature