US9187397, 1 US11608309, Compound Curcumin US10669227, Compound Curcumin BDBM191763 US9187406, Curcumin curcumin
ETHYL CURCUMIN BDBM50487886
US9187397, 1 (curcumin) BDBM191759
BDBM50487871 DI-O-CHLOROPROPIONYLETHYL CURCUMIN
DI-O-CHLOROACETYLETHYL CURCUMIN BDBM50487872
CHEMBL140 US20240131036, Example 8 CHEBI:3962 Curcumin US9409845, Table 1, Compound 21: curcumin BDBM50140172
4-(4-hydroxybenzylidene) curcumin CHEMBL260079 BDBM50619501
DI-O-(2-THIENOYL)CURCUMIN BDBM50487873
N-(3-Nitrophenylpyrazole)Curcumin BDBM50553256 CHEMBL258632
US9187397, 3a US9187397, 1 (curcumin) BDBM191758
CHEMBL140 Turmeric yellow (1E,6E)-1,7-bis(3-methoxy-4-oxidanyl-phenyl)hepta-1,6-diene-3,5-dione CURCUMIN MLS000069631 Natural yellow 3 Diferuloylmethane cid_969516 BDBM29532 (1E,6E)-1,7-bis(4-hydroxy-3-methoxy-phenyl)hepta-1,6-diene-3,5-dione SMR000058237 (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione Curcurmin
1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)hepta-1,4,6-trien-3-one curcumin II cid_5324476 BDBM50163744 CHEMBL179512 (1E,4Z,6E)-5-Hydroxy-1-(4-hydroxy-3-methoxy-phenyl)-7-(4-hydroxy-phenyl)-hepta-1,4,6-trien-3-one (1E,6E)-1-(4-Hydroxy-3-methoxy-phenyl)-7-(4-hydroxy-phenyl)-hepta-1,6-diene-3,5-dione demethoxycurcumin
5-Hydroxy-1,7-bis-(4-hydroxy-phenyl)-hepta-1,4,6-trien-3-one (1E,4Z,6E)-5-Hydroxy-1,7-bis-(4-hydroxy-phenyl)-hepta-1,4,6-trien-3-one CHEMBL131770 (1E,6E)-1,7-Bis-(4-hydroxy-phenyl)-hepta-1,6-diene-3,5-dione 5-Hydroxy-1,7-bis(4-hydroxyphenyl)hepta-1,4,6-trien-3-one BDBM50059989 curcumin III bis-demethoxycurcumin 1,7-bis(4-hydroxyphenyl)-3-hydroxy-1,3,6-heptatrien-5-one cid_5324473 CHEMBL105350 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione
(1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (E,E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione cid_5281767 (1E,4Z,6E)-5-Hydroxy-1,7-bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,4,6-trien-3-one 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one diferuloylmethane curcurmin (1E,6E)-1,7-Bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,6-diene-3,5-dione 5-Hydroxy-1,7-bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,4,6-trien-3-one ((E,E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) 1,7-Bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,6-diene-3,5-dione 1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione BDBM50067040 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadien-3,5-dione (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione 1,7-bis(4-hydroxy-3-methoxyphenyl)1,6-heptadiene-3,5-dione CHEMBL116438 (1E,4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,4,6-trien-3-one 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione curcumin I (1Z,6E)-1,7-Bis-(4-hydroxy-3-methoxy-phenyl)-hepta-1,6-diene-3,5-dione curcumine
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- Inhibition Assay Table 10: The efficacy of MMP-2 inhibition was as follows: compound 6>compound 7>compound 8. Although compound 6 showed similar efficacy as curcumin when comparing MMP-2 inhibitory potency, the amide-containing compounds are much more soluble than the famously insoluble curcumin. The amide-containing curcumin derivatives are much more potent inhibitors of MMP-13 (Collagenase-3) than curcumin and even more potent than compound 1 (Table 9 and 10).:
- ChEMBL_1982621 (CHEMBL4615883) Inhibition of Trypanosoma brucei rhodesain in presence of curcumin using Cbz-Phe-Arg-AMC as substrate incubated for 30 mins by fluorometric assay
- Cellular Firefly Luciferase Assay (AP-1) Curcumin is a known inhibitor of the AP-1 activation cascade. Therefore, modification of the structure of curcumin could lead to analogs with enhanced activity. The library consisting of three series of curcumin analogs were used to examine the role of the enone functionality in aryl systems where the spacer is 7-carbons (as in curcumin), 5-carbons or 3-carbons in length. In addition, the importance of aryl ring substituents was assessed. The AP-1 activities of curcumin and analogs were determined by a cellular firefly luciferase assay. This assay utilized a commercially available cell line (Panomics 293-luc cellular assay) developed for screening inhibitors of AP-1. This cell line is stably transfected with a luciferase reporter controlled by an AP-1 dependent promoter. The cell is stimulated with phorbol ester which activates AP-1. AP-1 then binds to one of three promoter regions on the cells DNA leading to the production of a luciferase enzyme. Luciferin is added to the cell lysates and the luciferase enzyme catalyzes a cleavage of luciferin leading to the emission of light.
- Inhibition of MMPs It has been observed that 50 and 100 μM concentrations of curcumin decreased TNFα production by endotoxin-stimulated human monocytes (HMs) in culture by 80-90% (lower concentrations of curcumin, 10 and 20 μM, had no effect). However, this inhibitory effect was associated with some precipitation of the curcumin in cell culture and with significant cytotoxicity. It was hypothesized that increasing the solubility of curcumin will: (i) enhance its efficacy as an inhibitor of cytokine expression, (ii) reduce its cytotoxicity, and (iii) preserve (perhaps even enhance; see below) its potency, as an MMP inhibitor (MMPI) compound, which was found to be similar to that of the Zn++ chelating compound, 1,10-O-phenanthroline (FIG. 1). However, it should be noted that excessive inhibition of MMP activity may not be desirable therapeutically because a minimal, or basal, level of MMPs may be necessary for optimal defense of the host.
- Inhibition Assay Table 1 shows the IC50 of curcumin, compound 1, and compound 2, compared to a standard Zn++ binding & MMPI (matrix metalloproteinase inhibitor), 1,10-O-phenanthroline (o-phen), against purified human PMN MMP-8 (from EMD biologics, Inc., Gibbstown, N.J.) using a synthetic octapeptide containing the collagenase-susceptible glycine-isoleucine peptide bond and measuring the tripeptide breakdown products by HPLC (Waters Alliance 2695 System with a reverse phase C-18 column). Compound 1 was an excellent MMPI with an IC50 equivalent to that of 1,10-O-phenanthroline, while compound 2, which lacked substituents on the aryl moieties, did not show a dose response.
- Cellular Firefly Luciferase Assay (NFkB) The NF-kB activities of curcumin and analogs were determined by a cellular firefly luciferase assay. This assay utilized a commercially available cell line (Panomics 293T-luc cellular assay) developed for screening inhibitors of NF-kB. This cell line is stably transfected with a luciferase reporter controlled by an NF-kB dependent promoter. The cell is stimulated with tumor necrosis factor alpha (TNFalpha) which activates NF-kB. NF-kB then binds to one of six promoter regions on the cell's DNA leading to the production of a luciferase enzyme. Luciferin is added to the cell lysates and the luciferase enzyme catalyzes a cleavage of luciferin leading to the emission of light.