Compositions and Methods for Cancer Treatment
AssigneeWomen and Infants Hospital of RI, Inc.
InventorsNarasimha Swamy, Hema Malini K. Sundaresha
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Abstract
Bromoacetoxycalcidiol (B3CD), which is structurally related to calcidiol, exhibits cytotoxic and apoptotic activity toward cancer cells, including highly aggressive neuroblastoma cells. A series of small molecules designed around the structure of B3CD is expected to have growth inhibitory and apoptogenic activities toward a wide range of malignancies. B3CD shows no apparent toxicity in vivo, indicating potential value as a chemotherapeutic agent which will be particularly useful in treating highly aggressive tumors.
Claims33
A method for inhibiting cancer cell proliferation, comprising administering to said cell an amount of a calcidiol derivative effective to inhibit proliferation of the cancer cell.
A method of inducing apoptosis in a cancer cell, comprising administering an amount of a calcidiol derivative to a cell effective to induce apoptosis in said cell.
A method for treating neuroblastoma or prostate cancer, comprising administering to a mammal in need thereof, an effective amount of a calcidiol derivative in a pharmaceutically acceptable vehicle.
A method for inhibiting TrkB signaling comprising administering to a mammal exhibiting neuroblastoma or prostate cancer an amount of a calcidiol derivative in a pharmaceutically acceptable vehicle effective to suppress BDNF and inhibit angiogenesis.
A method for treating or preventing a disorder associated with uncontrolled cell proliferation, the method comprising administering to a subject in need thereof a composition comprising an effective amount of a calcidiol derivative.
A novel calcidiol derivative of formula I:
- wherein:
- A1 is single or double bond;
- A2 is a single, double or triple bond;
- X1 and X2 are each independently H2 or CH2, provided X1 and X2 are not both ═CH2;
- and X1 can be substituted with CH2OR11
- wherein R11 is C(O)alkyl, C(O)aryl, or C(O)aralkyl;
- R1 is H, OH, or OSi(R10)3;
- Wherein R10 is alkyl, aryl, alkenyl, or aralkyl;
- R2 is O(CH2)nR12;
- Wherein R12 is halogen, haloalkyl, amino, alkyl amino, thiol, alkyl thio, hydroxyl, alkoxy, or alkenyl;
- n is an integer from 1-6;
- and any of the CH2 groups may be replaced by CO;
- R3 and R4 independently H, C1-C4 alkyl, hydroxyalkyl, or haloalkyl, or R3 and R4 taken together with C20 form C3-C6 cycloalkyl;
- R5 is H, C1-C4 alkyl, hydroxyalkyl, haloalkyl, or carbonyl;
- R6 and R7 are each independently alkyl or haloalkyl;
- R8 is H or biotin;
- R9 is H, hydroxyl, or halogen;
- and
- pharmaceutically acceptable esters, salts, solvates, clathrates, stereoisomers, enantiomers prodrugs thereof.
Dependencies are inferred from the claim text.