Cyclodepsipeptides with antineoplastic activity and methods of using to inhibit cancer and microbial growth
The present invention is directed to cyclodepsipeptide compounds having antineoplastic and/or antimicrobial activity, preferably Kitastatin 1. The present invention is further directed to methods of inhibiting cancer cell growth and/or microbial growth in a host inflicted therewith by administering cyclodepsipeptide compounds to the inflicted host.
1. A method of inhibiting cancer cell growth, wherein the cancer cell inhibited is selected from the group consisting of leukemia, pancreas, breast, CNS, lung-NSC, colon, or prostate cancer, in a host inflicted therewith comprising administering to a host a therapeutically effective amount of a compound having the structural formula:
or salts thereof, wherein
R 1 is CH 2 CH(CH 3 ) 2 or CH(CH 3 ) 2 ; and
R 2 is CHO or H.
2. The method of claim 1 , wherein R 1 is CH 2 CH(CH 3 ) 2 .
3. The method of claim 1 , wherein R 2 is H.
4. The method of claim 2 , wherein the compound has the structural formula:
5. The method of claim 1 , wherein the compound is administered in a pharmaceutical acceptable carrier and is administered in an amount of from about 1 mg to about 2000 mg.
6. The method of claim 5 , wherein the compound is administered in an amount of from about 100 mg to about 500 mg.
7. The method of claim 1 , wherein the compound is administered intravenous in an amount between 0.01 to about 20 mg/kg; intramuscular in an amount between 0.1 to about 50 mg/kg; orally in an amount 0.05 to about 100 mg/kg; intranasal instillation in an amount between 0.5 to about 100 mg/kg; or aerosol in an amount between 0.5 to about 100 mg/kg of host body weight.
8. A method of inhibiting bacterial growth comprising administering to a host infected with the bacterial growth a therapeutically effective amount of a compound having the structural formula:
or salt thereof, wherein the compound is in an amount sufficient to inhibit the microbial growth and, wherein
R 1 is CH 2 CH(CH 3 ) 2 or CH(CH 3 ) 2 ; and
R 2 is CHO or H.
9. The method of claim 8 , wherein the R 1 is CH 2 CH(CH 3 ) 2 .
10. The method of claim 8 , wherein R 2 is H.
11. The method of claim 9 , wherein the compound has structural formula:
12. The method of claim 8 , wherein the compound is in a pharmaceutically acceptable carrier, further comprising administering the compound to a host infected with a microbe in order to contact the microbe with the compound.
13. The method of claim 8 , wherein the compound inhibits the growth of at least one of the following: Enterococcus faecalis, Micrococcus luteus, Stenotrophomonas maltophilia, Staphylococcus aureus, Escherichia coli, Enterobacter cloacae, Streptococcus pneumoniae , or Neisseria gonorrhoeae.
14. A compound in substantially pure form having the structural formula
15. The compound of claim 14 , wherein the compound is denominated as Kitastatin 1 having the structural formula:
16. A composition comprising the compound of claim 14 and a pharmaceutically acceptable carrier.
17. The composition of claim 16 , wherein the compound is in a therapeutically effective amount sufficient to inhibit cancer cell growth.
18. The composition of claim 16 , wherein the compound inhibits the growth of at least one of the following: Enterococus faecalis, Micrococcus luteus, Stenotrophomonas maltophilia, Staphylococcus aureus, Escherichia coli, Enterobacter cloacae, Streptococcus pneumoniae, and Neisseria gonorrhoeae.