Daphnane diterpenoid resistant to prostate cancer and preparation method thereof
The invention relates to a daphnane diterpenoid resistant to a prostate cancer and a preparation method thereof. A daphnane diterpenoid compound as represented by formula (I) or formula (II) significantly inhibits the proliferation of various prostate cancer cells; the activities of some such compounds at a cellular level and an animal level are higher than that of the existing clinical targeting drug enzalutamide; and the daphnane diterpenoid compounds have strong synergistic effects when used in combination with the enzalutamide and are expected to become candidate drugs for treatment or adjuvant treatment of a castration-resistant prostate cancer.
1 . A method for treatment or adjuvant treatment of a castration-resistant prostate cancer in a patient, comprising:
determining whether the patient suffers from the castration-resistant prostate cancer, and
administering to the patient a therapeutic amount of a daphnane diterpenoid compound of formula I or a pharmaceutically acceptable salt thereof;
wherein:
in the formula I, a bond between C-1 and C-2 is a double bond, a bond between C-6 and C-7 is a single bond, and a bond between C-15 and C-16 is a double bond;
R 1 is absent;
R 2 is carbonyl;
R 3 is hydroxyl;
R 4 is hydroxyl;
R 5 is fluorine, chlorine, bromine, or iodine;
R 6 is fluorine, chlorine, bromine, or iodine;
R 7 is phenyl;
R 8 is absent; and
R 9 is hydrogen, hydroxyl, acetyl, benzoyl, isobutyryl, butyryl, or propionyl.
2 . The method according to claim 1 , further comprising administering to the patient at least one compound having a therapeutic effect on the castration-resistant prostate cancer.
3 . The method according to claim 2 , wherein the compound having the therapeutic effect on the castration-resistant prostate cancer is selected from the group consisting of enzalutamide, abiraterone, cyclophosphamide, adriamycin, docetaxel, mitoxantrone, and combinations thereof.
4 . A method for treatment or adjuvant treatment of a castration-resistant prostate cancer in a patient, comprising
determining whether the patient suffers from the castration-resistant prostate cancer, and
administering to the patient a therapeutic amount of a daphnane diterpenoid compound of formula IV or a pharmaceutically acceptable salt thereof;
wherein the compound of formula IV is selected from the group consisting of.
Compound
R 3
R 4
R 5
R 6
R 7
R 9
YH-45
OH
OBz
βCl
αOH
Ph
OAc
YH-46
OH
OBz
αOH
βCl
Ph
OAc
YH-47
OH
OH
βCl
αOH
Ph
OAc
YH-48
OH
OH
αOH
βCl
Ph
OAc
YH-49
OH
OH
βCl
αOH
Ph
OBz
YH-50
OH
OH
αOH
βCl
Ph
OBz
YH-52
OH
OH
βBr
αOH
Ph
OBz
YH-53
OH
OH
αOH
βBr
Ph
OBz
5 . The method according to claim 4 , further comprising administering to the patient at least one compound having a therapeutic effect on the castration-resistant prostate cancer.
6 . The method according to claim 4 , wherein the compound having the therapeutic effect on the castration-resistant prostate cancer is selected from the group consisting of enzalutamide, abiraterone, cyclophosphamide, adriamycin, docetaxel, mitoxantrone, and combinations thereof.