Isolation and structure of Cribrostatin 6
View Patent ↗Cribrostatin 6, a dark blue cancer cell growth inhibiting constituent of the Republic of Maldives marine sponge Cribrochalina sp. has been isolated, and its structure (shown below) elucidated, based on a combination of RMS, high field (500 MHz, HMBC, and GOESY experiments) 15N, 1 H- and 13C NMR, and X-ray crystal structure analyses. Cribrostatin 6 also was found to inhibit the growth of a number of pathogenic bacteria and fungi.
1. A compound and furthermore 9-ethoxy-3,8-dimethyl-imidazo[5,1-a]isoquinoline-7,10-dione.
2. The compound of claim 1 , having the following high filed (500 MHz) NMR assignments in CDCl 3
1 H
HMBC
GOESY
δ(mult,
13 C
j1xh = 140,
mix =
Position
J, #H)
and 15 N
jnxh = 8
COSY
.3
1
8.29s, 1H
125.68
C-3
2
3
137.64
4
5
7.90d,
124.73
C-3, C-6,
H-6
H-6,
7.5Hz, 1H
C-6a
H-11
6
7.26d,
107.73
C-6a, C-7,
H-5
7.5Hz, 1H
C-10a
6a
125.00
7
184.86
8
130.06
9
156.16
10
180.58
10a
123.49
10b
123.87
11
2.75s, 3H
12.57
C-3
H-5
12
2.06s, 3H
9.15
C-7, C-8,
C-9
13
4.40q,
69.64
C-9, C-14
H-14
6.9Hz, 2H
14
1.41t,
15.97
C-13
H-13
6.8Hz, 3H
N-4
189.5
N-2
273.9.
3. A composition comprising the compound of claim 1 and a pharmaceuticaly acceptable carrier therefor.
4. A method for treating neoplastic disease selected from the group consisting of pancreatic cancer, breast cancer, central nervous system cancer,lung cancer colon cancer, prostate cancer and leukemia, comprising administering a therapeutically effective amount of the compound of claim 1 to a human or animal subject.
5. A method for treating bacterial infections selected from the group consisting of Micrococcus lutes, Staphylococcus aureus, Enterococcus faecalis, Bacillus sublilis, Streptococcus pneumoniae , Group A Streptococcus, Stenotrophonionas maltophilia, Escherichia coli, Enterobacter cloacae and Neisseria gonorrhoeae , comprising administering a therapeutically effective amount of the compound of claim 1 to a human or animal subject.
6. A method for treating fungal infections selected from the group consisting of Candida albicans and Cryptococcus neoformans , comprising administering a therapeutically effective amount of the compound of claim 1 to a human or animal subjet.
7. A method for purifying cribrostating 6 (9-ethoxy-3,8-dimethyl-imidazo[5,1-a]isoquinoline-7,10-dione) by:
(a) fractionating extract of blue marine sponge Cribochalina sp. Via successive elutions with CH 3 OH, CH 2 Cl 2 —CH 3 OH (3:2), hexane-toluene —CH 3 OH (3:1:1) and hexane/i-PrOH—CH 3 OH (8:1:1),
(b) triturating the blue fraction resulting from step (a) with less polar phase of the system hexane-EtOAc—CH 3 OH-water (700:300:150:60),
(c) filtering the solution and (d) obtaining a solid.