In:
Archiv der Pharmazie, Wiley, Vol. 354, No. 11 ( 2021-11)
Abstract:
Novel series of imidazo[2,1‐ b ]thiazole analogs were designed, synthesized, and biologically evaluated as indoleamine 2,3‐dioxygenase (IDO1) inhibitors. Imidazo[2,1‐ b ]thiazoles 6 , 7 , and 8 showed inhibitory profiles against IDO1 at IC 50 values of 68.48, 82.39, and 48.48 nM, respectively, compared with IDO5L at IC 50 67.40 nM. Benzo[ d ]imidazo[2,1‐ b ]thiazoles 17 , 20 , and 22 showed promising IDO1 inhibition at IC 50 values of 53.58, 53.16, and 57.95 nM, respectively. Compound 7 showed a growth‐inhibitory profile at GI of 39.33% against the MCF7 breast cancer cell line, while 8 proved lethal to ACHN renal cancer cells. Cells treated with compounds 17 and 22 showed a typical apoptosis pattern of DNA fragments that reflected the G0/G1, S, and G2/M phases of the cell cycle, together with a pre‐G1 phase corresponding to apoptotic cells, which indicates that cell growth arrest occurred at the S phase. Molecular modeling simulations validated the potential of benzo[ d ]imidazo[2,1‐ b ]thiazole analogs to chelate iron(III) within the IDO1 binding pocket and, hence, to have a better binding affinity via hydrophobic–hydrophobic interactions.
Type of Medium:
Online Resource
ISSN:
0365-6233
,
1521-4184
DOI:
10.1002/ardp.v354.11
DOI:
10.1002/ardp.202100202
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
1496815-0
SSG:
15,3
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