Phospholipid ether analogs as cancer-targeting drug vehicles
The present invention is directed to therapeutic compounds capable of targeting cancer cells and cancer stem cells. The present invention is further directed to compositions comprising these therapeutic compounds and methods of treating cancer comprising administering these therapeutic compounds.
1. A method of treating cancer comprising administering an effective amount of a therapeutic compound having a formula A-B-D to a subject with cancer,
wherein
A is at least one compound of formula (I),
at least one compound of formula (II),
at least one compound of formula (III)
or a combination thereof,
wherein W is selected from the group consisting of an aryl, a C 1 -C 6 alkyl, an alkenyl, an optionally substituted C 3 -C 6 cycloalkyl, an optionally substituted C 3 -C 6 heterocycloalkyl,
wherein R is H or an alkyl and wherein m is an integer from 12 to 24;
B is a linker compound selected from a bond and a compound of formula (IV),
Y—(CH 2 ) n —Z (IV),
wherein:
Y is bound to A;
Z is bound to D;
Y is selected from the group consisting of a bond, O, NH, C═O, NHSO 2 O, and OC(═O)O;
Z is selected from the group consisting of O, NH, C═O, C(═O)O, C(═O)NH, SO 2 , OC(═O)OCH 2 , and —S—S—; and
n is an integer from 0 to 6; and
D is an anti-cancer drug selected from the group consisting of paclitaxel, irinotecan, topotecan, gemcitabine, cisplatin, geldanamycin, and mertansine; and
wherein the cancer is selected from the group consisting of adrenal cancer, glioblastoma, melanoma, multiple myeloma, ovarian cancer, sarcoma, uterine cancer, hepatocellular carcinoma, cervical-HPV cancer, esophageal cancer, neuroblastoma, head and neck cancer, and a combination thereof.
2. The method of claim 1 wherein the cancer comprises cancer stem cells.
3. The method of claim 1 wherein the cancer is recurrent.
4. A method of treating cancer comprising administering an effective amount of a therapeutic compound to a subject with cancer,
wherein the therapeutic compound is selected from the group consisting of:
wherein n is an integer from 0 to 6 and X is O or NH; and
wherein the cancer is selected from the group consisting of adrenal cancer, glioblastoma, melanoma, multiple myeloma, ovarian cancer, sarcoma, uterine cancer, hepatocellular carcinoma, cervical-HPV cancer, esophageal cancer, neuroblastoma, head and neck cancer, and a combination thereof.
5. A method of treating cancer comprising administering an effective amount of a therapeutic compound of Formula (V) to a subject with cancer,
wherein the cancer is selected from the group consisting of adrenal cancer, glioblastoma, melanoma, multiple myeloma, ovarian cancer, sarcoma, uterine cancer, hepatocellular carcinoma, cervical-HPV cancer, esophageal cancer, neuroblastoma, head and neck cancer, and a combination thereof.
6. The method of claim 1 , wherein
A is a compound of formula (I), wherein W is
and m is 18;
B is a compound of formula (IV), wherein Y is C═O and Z is C═O, C(═O)NH or C(═O)O and n is 3 or 4; and
D is paclitaxel.
7. The method of claim 1 , wherein
A is a compound of formula (I), wherein W is
and m is 18;
B is a bond or a compound of formula (IV), wherein Y is C═O, Z is NH and n is 1 or 3; and
D is geldanamycin.
8. The method of claim 1 , wherein
A is a compound of formula (I), wherein W is
and m is 18;
B is a bond; and
D is mertansine.
9. The method of claim 1 , wherein the cancer is glioblastoma, melanoma, multiple myeloma, neuroblastoma, head and neck cancer, fibrosarcoma, or a combination thereof.
10. The method of claim 4 , wherein the cancer is glioblastoma, melanoma, multiple myeloma, neuroblastoma, head and neck cancer, fibrosarcoma, or a combination thereof.
11. The method of claim 5 , wherein the cancer is glioblastoma, melanoma, multiple myeloma, neuroblastoma, head and neck cancer, fibrosarcoma, or a combination thereof.