Pederin and psymberin agents
Compounds that include a pederin, psymberin or pederin/psymberin chimera scaffold. The pederin scaffold includes a substituent at the C10 and/or C13 position that may include a linker that may be conjugated to a targeting moiety. The psymberin scaffold includes a substituent at the C8 and/or C11 positions that may include a linker that may be conjugated to a targeting moiety. The pederin/psymberin chimera scaffold includes a substituent at the C10 and/or C13 position that may include a linker that may be conjugated to a targeting moiety. The pederin, psymberin or pederin/psymberin chimera scaffold may be modified to include substituents at positions other than the C10 or C13 of pederin, or the C8 and C11 of psymberin.
1. A compound, or a pharmaceutically acceptable salt or ester thereof, comprising:
A-L
wherein A comprises pederin, psymberin, or a pederin/psymberin chimera; and
L comprises a linker that includes a reactive functional group that can bind to a targeting moiety, wherein L is bonded at C10 and/or C13 position of pederin, or the pederin/psymberin chimera, or L is bonded at C8 and/or C11 position of psymberin, and wherein the linker includes a divalent radical selected from an alkanediyl, a cycloalkanediyl, an aryldiyl, a heteroaryldiyl, and an alkanearyldiyl.
2. The compound of claim 1 , or a pharmaceutically acceptable salt or ester thereof, having a formula of:
wherein at least one of R 1 or R 2 includes the linker that includes a reactive functional group that can bind to a targeting moiety; or a formula of:
wherein at least one of R 3 or R 4 includes the linker that includes a reactive functional group that can bind to a targeting moiety; or a formula of:
wherein at east one of R 5 or R 6 includes the linker that includes a reactive functional group that can bind to a targeting moiety wherein the linker in R 1 , R 2 , R 3 , R 4 , R 5 and R 6 includes a divalent radical selected from an alkanediyl, a cycloalkanediyl, an aryldiyl, a heteroaryldiyl and an alkanearyldiyl.
3. The compound of claim 2 , wherein at least one of R 1 or R 2 has the structure —O-L wherein O is an oxygen atom and L is a linker, or at least one of R 3 or R 4 has the structure —O-L wherein O is an oxygen atom and L is a linker, or at least one of R 5 or R 6 has the structure —O-L wherein O is an oxygen atom and L is a linker.
4. The compound of claim 1 , wherein the targeting moiety is an antibody, a liposome, or a dendrimer.
5. The compound of claim 1 , wherein the reactive functional group is an amine-reactive group, a thiol-reactive group, a carboxylate-reactive group, a hydroxyl reactive-group, an aldehyde- or ketone-reactive group, or an active hydrogen-reactive group.
6. The compound of claim 1 , wherein the reactive functional group is selected from isothiocyanate, isocyanate, acyl azide, an N-hydroxysuccinimidyl ester, acid chloride, aldehyde, glyoxal, epoxide, oxirane, carbonate, imidoester, carbodiimide, haloacetyl, alkyl halide, maleimide, aziridine, acryloyl, pyridyl disulfide, TNB-thiol, diazoalkane, diazoacetyl, carbonyldiimidazole, carbonyldiimidazole, N,N′-disuccinimidyl carbonate, N-hydroxysuccinimidyl chloroformate, hydrazine, and diazonium.
7. The compound of claim 3 , wherein R 1 has the structure —O-L, and R 2 is an alkoxy methoxy.
8. The compound of claim 1 , wherein R 1 has the structure —O-L, and the linker includes a divalent radical selected from an alkanediyl or a heteroaryldiyl.
9. The compound of claim 1 , wherein the reactive functional group is a maleimide.
10. The compound of claim 3 , wherein R 1 has the structure —O-L, the linker includes an alkanediyl coupled to a heteroaryldiyl, and reactive functional group includes a maleimide.
11. A pharmaceutical composition comprising at least one compound of claim 1 , and at least one pharmaceutically acceptable additive.
12. A method for treating a neoplasm in a subject comprising administering to the subject at least one compound of claim 1 .
13. The method of claim 12 , wherein the neoplasm is cancer.
14. The method of claim 13 , wherein the cancer is colon cancer.
15. The compound of claim 1 , wherein L has the structure —O-linker.
16. The compound of claim 1 , wherein the reactive functional group is olefin, acetylene, alcohol, phenol, ether, oxide, halide, aldehyde, ketone, carboxylic acid, ester, amide, cyanate, isocyanate, thiocyanate, isothiocyanate, amine, hydrazine, hydrazone, hydrazide, diazo, diazonium, nitro, nitrile, mercaptan, sulfide, disulfide, sulfoxide, sulfone, sulfonic acid, sulfinic acid, acetal, ketal, anhydride, sulfate, sulfenic acid, isonitrile, amidine, imide, imidate, nitrone, hydroxylamine, oxime, hydroxamic acid, thiohydroxamic acid, allene, ortho ester, sulfite, enamine, ynamine, urea, pseudourea, semicarbazide, carbodiimide, carbamate, imine, azide, azo, azoxy, or nitroso.
17. The compound of claim 16 , wherein the reactive group is azide.