Synthesis and antiproliferative activity evaluation of steroidal imidazo[1,2-a]pyridines.
An elegant approach to unknown steroidal imidazo[1,2-a]pyridine hybrids is disclosed. Unique derivatives of androstene and estrane series containing imidazo[1,2-a]pyridine motifs were prepared from 17-ethynyl steroids in good yields via copper-catalyzed cascade aminomethylation/cycloisomerization with imines. The synthesized compounds were screened for cytotoxicity against human breast (MCF-7, MDA-MB-231, HBL-100, MDA-MB-453) and prostate (LNCaP-LN3, PC-3, DU 145) cancer cell lines. The majority of tested compounds showed activities at μM level in breast cancer cells. The hormone-responsive breast cancer cells MCF-7 were more sensitive to novel compounds than ERα-negative cells; in particular, compounds 6a,b exhibited promising cytotoxicity against this cell line with the IC50 values in the range of 3-4μM. Furthermore, compound 4a showed remarkable effects as a selective ERα receptor modulator.
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russia.
Irina V
IV
Rassokhina
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russia. Electronic address: yavolkova@gmail.com.
Yulia A
YA
Volkova
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russia.
Andrey S
AS
Kozlov
N. N. Blokhin Russian Cancer Research Center, Kashirskoye shosse 24, 115478 Moscow, Russia.
Alexander M
AM
Scherbakov
N. N. Blokhin Russian Cancer Research Center, Kashirskoye shosse 24, 115478 Moscow, Russia.
Olga E
OE
Andreeva
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russia.
Valerik Z
VZ
Shirinian
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russia.
Igor V
IV
Zavarzin
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry*
D000970:Antineoplastic Agents; D011725:Pyridines; D013256:Steroids; C023666:pyridine
17-Ethynyl steroids; Estrogen receptor α; Hormone-dependent cancers; Hybrids; Imidazo[1,2-a]pyridines