Thiosemicarbazone compounds and uses thereof
Provided, inter alia, are thiosemicarbazone compounds, metal complexes of thiosemicarbazone compounds, pharmaceutical compositions, and methods for treating cancer.
1 . A compound of Formula (Ia), a pharmaceutically acceptable salt thereof, a metal complex thereof, or a pharmaceutically acceptable salt of a metal complex thereof:
wherein:
R 1 is unsubstituted C 1-4 alkyl;
R 2 is hydrogen or unsubstituted C 1-4 alkyl; and
R 4 , R 5 , and R 6 are each independently hydrogen, fluorine, chlorine, bromine, iodine, —NH 2 , N(C 1-4 alkyl)(C 1-4 alkyl), wherein when R 2 is H, R 4 -R 6 are all not H.
2 . The compound of claim 1 , wherein
R 1 is —CH 3 or —CH 2 CH 3 ;
R 2 is hydrogen, —CH 3 , or —CH 2 CH 3 ; and
R 4 , R 5 , and R 6 are each independently hydrogen, fluorine, chlorine, bromine, iodine, —NH 2 , —NHCH 3 , —NHCH 2 CH 3 , —N(CH 3 ) 2 , —N(CH 3 )(CH 2 CH 3 ), or —N(CH 2 CH 3 ) 2 .
3 . The compound of claim 1 , wherein
R 1 is —CH 3 or —CH 2 CH 3 ;
R 2 is hydrogen, —CH 3 , or —CH 2 CH 3 ; and
R 4 , R 5 , and R 6 are each independently hydrogen, fluorine, NH 2 , —NHCH 3 , —NHCH 2 CH 3 , —N(CH 3 ) 2 , —N(CH 3 )(CH 2 CH 3 ), or —N(CH 2 CH 3 ) 2 .
4 . The compound of claim 1 , wherein
R 1 is —CH 3 or CH 2 CH 3 ;
R 2 is —CH 3 or CH 2 CH 3 ;
R 4 and R 6 are each independently hydrogen, fluorine, chlorine, bromine, or iodine; and
R 5 is hydrogen, NH 2 , —NHCH 3 , —NHCH 2 CH 3 , —N(CH 3 ) 2 , —N(CH 3 )(CH 2 CH 3 ), or —N(CH 2 CH 3 ) 2 .
5 . The compound of claim 1 , wherein
R 1 is —CH 3 or CH 2 CH 3 ;
R 2 is —CH 3 or CH 2 CH 3 ;
R 4 and R 6 are each independently hydrogen or fluorine; and
R 5 is hydrogen, NH 2 , —NHCH 3 , or —NHCH 2 CH 3 .
6 . The compound of claim 1 having the structure:
7 . The compound of claim 1 having the structure:
8 . The compound of claim 1 having the structure:
9 . A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
10 . A composition comprising: (i) the compound of claim 1 , and (ii) copper, a copper salt, zinc, a zinc salt, cobalt, a cobalt salt, nickel, a nickel salt, magnesium, a magnesium salt, iron, an iron salt, manganese, a manganese salt, gallium, a gallium salt, germanium, a germanium salt, calcium, a calcium salt, or a combination of two or more thereof.
11 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound of claim 1 , wherein the cancer is prostate cancer, small cell lung carcinoma, pancreatic ductal adenocarcinoma, or leukemia.
12 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .
13 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of claim 1 , wherein the cancer is prostate cancer, small cell lung carcinoma, pancreatic ductal adenocarcinoma, or leukemia.