Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1- b ]thiazole derivatives

Mohammed S. Abdel-Maksoud, Mi Ryeong Kim, Mohammed I. El-Gamal, Mahmoud M. Gamal El-Din, Jinsung Tae, Hong Seok Choi, Kyung Tae Lee, Kyung Ho Yoo, Chang Hyun Oh

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Design and synthesis of a new series of 5,6-diarylimidazo[2,1-b]thiazole derivatives possessing terminal aryl sulfonamide moiety are described. Their in vitro antiproliferative activities against a panel of 57 human cancer cell lines of nine different cancer types were tested at the NCI. Compounds 8a, 8b, 8n, 8q, 8t, and 8u showed the highest mean % inhibition values over the 57 cell line panel at 10 1/4M, and they were further tested in 5-dose testing mode to determine their IC50 values. Among the six compounds, compound 8u possessing terminal para-hydroxybenzenesulfonamido moiety and ethylene linker showed the highest potency. It demonstrated superior potency than Sorafenib against eight different cell lines, and was equipotent to Sorafenib against COLO 205 colon cancer cell line. Its IC50 values over NCI-H460 non-small cell lung cancer cell line and MCF7 breast cancer cell line were 0.845 1/4M and 0.476 1/4M, respectively. Compounds 8a, 8b, 8q, 8t, and 8u showed high selectivity indices towards cancer cells over L132 normal lung cell line. Compound 8u showed potential inhibitory effects over the components of ERK pathway. Its IC50 value over V600E-B-RAF and C-RAF kinases were 39.9 nM and 19.0 nM, respectively.

Original languageEnglish
Pages (from-to)453-463
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume95
DOIs
Publication statusPublished - 2015 May 5

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Phosphotransferases
Cells
Derivatives
Cell Line
Inhibitory Concentration 50
Thiazoles
Neoplasms
MAP Kinase Signaling System
Sulfonamides
imidazo(2,1-b)thiazole
In Vitro Techniques
Non-Small Cell Lung Carcinoma
Colonic Neoplasms
Breast Neoplasms
Lung
Testing
sorafenib

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Abdel-Maksoud, Mohammed S. ; Kim, Mi Ryeong ; El-Gamal, Mohammed I. ; Gamal El-Din, Mahmoud M. ; Tae, Jinsung ; Choi, Hong Seok ; Lee, Kyung Tae ; Yoo, Kyung Ho ; Oh, Chang Hyun. / Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1- b ]thiazole derivatives. In: European Journal of Medicinal Chemistry. 2015 ; Vol. 95. pp. 453-463.
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Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1- b ]thiazole derivatives. / Abdel-Maksoud, Mohammed S.; Kim, Mi Ryeong; El-Gamal, Mohammed I.; Gamal El-Din, Mahmoud M.; Tae, Jinsung; Choi, Hong Seok; Lee, Kyung Tae; Yoo, Kyung Ho; Oh, Chang Hyun.

In: European Journal of Medicinal Chemistry, Vol. 95, 05.05.2015, p. 453-463.

Research output: Contribution to journalArticle

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AU - Abdel-Maksoud, Mohammed S.

AU - Kim, Mi Ryeong

AU - El-Gamal, Mohammed I.

AU - Gamal El-Din, Mahmoud M.

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AU - Oh, Chang Hyun

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