8-[5-(5,7-Dihydroxy-4-oxo-4H-chromen-2-yl)-2-hydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxy-phenyl)-chromen-4-one

ID: ALA63354

Chembl Id: CHEMBL63354

Max Phase: Preclinical

Molecular Formula: C30H18O10

Molecular Weight: 538.46

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Amentoflavone

Canonical SMILES:  O=c1cc(-c2ccc(O)c(-c3c(O)cc(O)c4c(=O)cc(-c5ccc(O)cc5)oc34)c2)oc2cc(O)cc(O)c12

Standard InChI:  InChI=1S/C30H18O10/c31-15-4-1-13(2-5-15)24-12-23(38)29-21(36)10-20(35)27(30(29)40-24)17-7-14(3-6-18(17)33)25-11-22(37)28-19(34)8-16(32)9-26(28)39-25/h1-12,31-36H

Standard InChI Key:  YUSWMAULDXZHPY-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA63354

   AMENTOFLAVONE

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

Calculated Properties

Molecular Weight: 538.46

Molecular Weight (Monoisotopic): 538.0900

AlogP: 5.13

#Rotatable Bonds: 3

Polar Surface Area: 181.80

Molecular Species: ACID

HBA: 10

HBD: 6

#RO5 Violations: 3

HBA (Lipinski): 10

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 6.09

CX Basic pKa: ┄

CX LogP: 5.09

CX LogD: 2.95

Aromatic Rings: 6

Heavy Atoms: 40

QED Weighted: 0.18

Np Likeness Score: 1.23

References

1. Lin YM, Flavin MT, Cassidy CS, Mar A, Chen FC..  (2001)  Biflavonoids as novel antituberculosis agents.,  11  (16): [PMID:11514148] [10.1016/s0960-894x(01)00382-1]

2. Hanrahan JR, Chebib M, Davucheron NL, Hall BJ, Johnston GA..  (2003)  Semisynthetic preparation of amentoflavone: A negative modulator at GABA(A) receptors.,  13  (14): [PMID:12824018] [10.1016/s0960-894x(03)00434-7]

3. Chen J, Chang HW, Kim HP, Park H..  (2006)  Synthesis of phospholipase A2 inhibitory biflavonoids.,  16  (9): [PMID:16504502] [10.1016/j.bmcl.2006.01.117]

4. Zeng GZ, Tan NH, Hao XJ, Mu QZ, Li RT..  (2006)  Natural inhibitors targeting osteoclast-mediated bone resorption.,  16  (24): [PMID:17027271] [10.1016/j.bmcl.2006.09.042]

5. Moon TC, Quan Z, Kim J, Kim HP, Kudo I, Murakami M, Park H, Chang HW..  (2007)  Inhibitory effect of synthetic C-C biflavones on various phospholipase A(2)s activity.,  15  (22): [PMID:17826099] [10.1016/j.bmc.2007.07.054]

6. Katavic PL, Lamb K, Navarro H, Prisinzano TE..  (2007)  Flavonoids as opioid receptor ligands: identification and preliminary structure-activity relationships.,  70  (8): [PMID:17685652] [10.1021/np070194x]

7. Lee CW, Choi HJ, Kim HS, Kim DH, Chang IS, Moon HT, Lee SY, Oh WK, Woo ER..  (2008)  Biflavonoids isolated from Selaginella tamariscina regulate the expression of matrix metalloproteinase in human skin fibroblasts.,  16  (2): [PMID:18029185] [10.1016/j.bmc.2007.10.036]

8. Pattamadilok D, Suttisri R..  (2008)  Seco-terpenoids and other constituents from Elateriospermum tapos.,  71  (2): [PMID:18179177] [10.1021/np070629g]

9. Hayashi T, Sawa K, Kawasaki M, Arisawa M, Shimizu M, Morita N..  (1988)  Inhibition of cow's milk xanthine oxidase by flavonoids.,  51  (2): [PMID:3379415] [10.1021/np50056a030]

10. Sun CM, Syu WJ, Huang YT, Chen CC, Ou JC..  (1997)  Selective cytotoxicity of ginkgetin from Selaginella moellendorffii.,  60  (4): [PMID:9134745] [10.1021/np960608e]

11. Lin YM, Anderson H, Flavin MT, Pai YH, Mata-Greenwood E, Pengsuparp T, Pezzuto JM, Schinazi RF, Hughes SH, Chen FC..  (1997)  In vitro anti-HIV activity of biflavonoids isolated from Rhus succedanea and Garcinia multiflora.,  60  (9): [PMID:9322359] [10.1021/np9700275]

12. Li XC, Joshi AS, ElSohly HN, Khan SI, Jacob MR, Zhang Z, Khan IA, Ferreira D, Walker LA, Broedel SE, Raulli RE, Cihlar RL..  (2002)  Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies.,  65  (12): [PMID:12502337] [10.1021/np020289t]

13. Baggett S, Protiva P, Mazzola EP, Yang H, Ressler ET, Basile MJ, Weinstein IB, Kennelly EJ..  (2005)  Bioactive benzophenones from Garcinia xanthochymus fruits.,  68  (3): [PMID:15787435] [10.1021/np0497595]

14. Lee JS, Cho YS, Park EJ, Kim J, Oh WK, Lee HS, Ahn JS..  (1998)  Phospholipase Cgamma1 inhibitory principles from the sarcotestas of Ginkgo biloba.,  61  (7): [PMID:9677265] [10.1021/np970367q]

15. Lee JS, Kim J, Kim BY, Lee HS, Ahn JS, Chang YS..  (2000)  Inhibition of phospholipase cgamma1 and cancer cell proliferation by triterpene esters from Uncaria rhynchophylla.,  63  (6): [PMID:10869194] [10.1021/np990478k]

16. Lin LC, Kuo YC, Chou CJ..  (2000)  Cytotoxic biflavonoids from Selaginella delicatula.,  63  (5): [PMID:10843573] [10.1021/np990538m]

17. Saponara R, Bosisio E..  (1998)  Inhibition of cAMP-phosphodiesterase by biflavones of Ginkgo biloba in rat adipose tissue.,  61  (11): [PMID:9834158] [10.1021/np970569m]

18. Lale A, Herbert JM, Augereau JM, Billon M, Leconte M, Gleye J..  (1996)  Ability of different flavonoids to inhibit the procoagulant activity of adherent human monocytes.,  59  (3): [PMID:8882428] [10.1021/np960057s]

19. Nahrstedt A, Butterweck V..  (2010)  Lessons learned from herbal medicinal products: the example of St. John's Wort (perpendicular).,  73  (5): [PMID:20408551] [10.1021/np1000329]

20. Sasaki H, Miki K, Kinoshita K, Koyama K, Juliawaty LD, Achmad SA, Hakim EH, Kaneda M, Takahashi K..  (2010)  beta-Secretase (BACE-1) inhibitory effect of biflavonoids.,  20  (15): [PMID:20598535] [10.1016/j.bmcl.2010.06.021]

21. Ryu YB, Jeong HJ, Kim JH, Kim YM, Park JY, Kim D, Nguyen TT, Park SJ, Chang JS, Park KH, Rho MC, Lee WS..  (2010)  Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition.,  18  (22): [PMID:20934345] [10.1016/j.bmc.2010.09.035]

22. PubChem BioAssay data set, 

23. Park NH, Lee CW, Bae JH, Na YJ..  (2011)  Protective effects of amentoflavone on Lamin A-dependent UVB-induced nuclear aberration in normal human fibroblasts.,  21  (21): [PMID:21917453] [10.1016/j.bmcl.2011.08.067]

24. Liu MM, Zhou L, He PL, Zhang YN, Zhou JY, Shen Q, Chen XW, Zuo JP, Li W, Ye DY..  (2012)  Discovery of flavonoid derivatives as anti-HCV agents via pharmacophore search combining molecular docking strategy.,  52  [PMID:22445328] [10.1016/j.ejmech.2012.03.002]

25. Yu MS, Lee J, Lee JM, Kim Y, Chin YW, Jee JG, Keum YS, Jeong YJ..  (2012)  Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13.,  22  (12): [PMID:22578462] [10.1016/j.bmcl.2012.04.081]

26. Tung NH, Uto T, Sakamoto A, Hayashida Y, Hidaka Y, Morinaga O, Lhieochaiphant S, Shoyama Y..  (2013)  Antiproliferative and apoptotic effects of compounds from the flower of Mammea siamensis (Miq.) T. Anders. on human cancer cell lines.,  23  (1): [PMID:23206866] [10.1016/j.bmcl.2012.10.127]

27. Pesca MS, Dal Piaz F, Sanogo R, Vassallo A, Bruzual de Abreu M, Rapisarda A, Germanò MP, Certo G, De Falco S, De Tommasi N, Braca A..  (2013)  Bioassay-guided isolation of proanthocyanidins with antiangiogenic activities.,  76  (1): [PMID:23268742] [10.1021/np300614u]

28. Nguyen PH, Ji DJ, Han YR, Choi JS, Rhyu DY, Min BS, Woo MH..  (2015)  Selaginellin and biflavonoids as protein tyrosine phosphatase 1B inhibitors from Selaginella tamariscina and their glucose uptake stimulatory effects.,  23  (13): [PMID:25907369] [10.1016/j.bmc.2015.04.007]

29. Sasaki H, Kitoh Y, Tsukada M, Miki K, Koyama K, Juliawaty LD, Hakim EH, Takahashi K, Kinoshita K..  (2015)  Inhibitory activities of biflavonoids against amyloid-β peptide 42 cytotoxicity in PC-12 cells.,  25  (14): [PMID:26004578] [10.1016/j.bmcl.2015.04.106]

30. Cai S, Risinger AL, Nair S, Peng J, Anderson TJ, Du L, Powell DR, Mooberry SL, Cichewicz RH..  (2016)  Identification of Compounds with Efficacy against Malaria Parasites from Common North American Plants.,  79  (3): [PMID:26722868] [10.1021/acs.jnatprod.5b00874]

31. Ayoub IM, Korinek M, Hwang TL, Chen BH, Chang FR, El-Shazly M, Singab ANB..  (2018)  Probing the Antiallergic and Anti-inflammatory Activity of Biflavonoids and Dihydroflavonols from Dietes bicolor.,  81  (2): [PMID:29381070] [10.1021/acs.jnatprod.7b00476]

32. Taniguchi K, Funasaki M, Kishida A, Sadhu SK, Ahmed F, Ishibashi M, Ohsaki A..  (2018)  Two new coumarins and a new xanthone from the leaves of Rhizophora mucronata.,  28  (6): [PMID:29475587] [10.1016/j.bmcl.2018.02.022]

33. Wang CG, Yao WN, Zhang B, Hua J, Liang D, Wang HS..  (2018)  Lung cancer and matrix metalloproteinases inhibitors of polyphenols from Selaginella tamariscina with suppression activity of migration.,  28  (14): [PMID:29921475] [10.1016/j.bmcl.2018.06.024]

34. Li YR, Li GH, Zhou MX, Xiang L, Ren DM, Lou HX, Wang XN, Shen T..  (2018)  Discovery of natural flavonoids as activators of Nrf2-mediated defense system: Structure-activity relationship and inhibition of intracellular oxidative insults.,  26  (18): [PMID:30227999] [10.1016/j.bmc.2018.09.010]

35. Ren Y, de Blanco EJC, Fuchs JR, Soejarto DD, Burdette JE, Swanson SM, Kinghorn AD..  (2019)  Potential Anticancer Agents Characterized from Selected Tropical Plants.,  82  (3): [PMID:30830783] [10.1021/acs.jnatprod.9b00018]

36. Sirimangkalakitti N, Juliawaty LD, Hakim EH, Waliana I, Saito N, Koyama K, Kinoshita K..  (2019)  Naturally occurring biflavonoids with amyloid β aggregation inhibitory activity for development of anti-Alzheimer agents.,  29  (15): [PMID:31138471] [10.1016/j.bmcl.2019.05.020]

37. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]

38. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]

39. Silva LR,da Silva Santos-Júnior PF,de Andrade Brandão J,Anderson L,Bassi ÊJ,Xavier de Araújo-Júnior J,Cardoso SH,da Silva-Júnior EF.  (2020)  Druggable targets from coronaviruses for designing new antiviral drugs.,  28  (22.0): [PMID:33007557] [10.1016/j.bmc.2020.115745]

40. Long H, Hu X, Wang B, Wang Q, Wang R, Liu S, Xiong F, Jiang Z, Zhang XQ, Ye WC, Wang H..  (2021)  Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer.,  64  (16.0): [PMID:34404206] [10.1021/acs.jmedchem.1c00735]

41. Wang B, Hu X, Wang R, Long H, Wang H..  (2022)  Evaluation of amentoflavone metabolites on PARP-1 inhibition and the potentiation on anti-proliferative effects of carboplatin in A549 cells.,  56  [PMID:34843914] [10.1016/j.bmcl.2021.128480]

42. Xie Y, Zhou X, Li J, Yao XC, Liu WL, Xu PS, Tan GS..  (2022)  Cytotoxic effects of the biflavonoids isolated from Selaginella trichoclada on MCF-7 cells and its potential mechanism.,  56  [PMID:34875389] [10.1016/j.bmcl.2021.128486]

43. Zhang J, Gao Y, Zhang Z, Zhao J, Jia W, Xia C, Wang F, Liu T..  (2022)  Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment.,  65  (24.0): [PMID:36512711] [10.1021/acs.jmedchem.2c01352]

Source

Source(3):

• Scientific Literature
• PubChem BioAssays
• SARS-CoV-2 Screening Data 2020-21