Abstract
This article described the synthesis and in vitro antiproliferative activities a series of 6-(4-fluorophenyl)-5-(2-substituted pyrimidin-4-yl)imidazo[2,1-b]thiazole derivatives. The nine target compounds were tested for in vitro antitumor effect against a panel of 55 cell lines of nine different cancer types at the NCI, and their activities were compared with that of Sorafenib as a reference standard drug. Compounds 1d and 1e possessing terminal arylamide moiety exerted superior potencies than Sorafenib against different cancer cell lines. Both compounds were more potent than Sorafenib against UO-31 renal cancer cell line and MCF7 breast cancer cell line. Compound 1d was also more potent than Sorafenib against COLO 205 colon cancer cell line, and compound 1e showed higher potency than Sorafenib against OVCAR-3 ovarian cancer cell line and DU-145 prostate cancel cell line also. For instance, the IC50 value of compound 1e against DU-145 prostate cancer cell line was 1.04 μM, which is threefold more potent than Sorafenib.
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Abdel-Maksoud MS, Kim MR, El-Gamal MI, Gamal El-Din MM, Tae J, Choi HS, Lee KT, Yoo KH, Oh CH (2015) Design, synthesis, in vitro antiproliferative evaluation, and kinase inhibitory effects of a new series of imidazo[2,1-b]thiazole derivatives. Eur J Med Chem 95:453–463
Andreani A, Leoni A, Locatelli A, Morigi R, Rambaldi M, Recanatini M, Garaliene V (2000) Potential antitumor agents. part 29: synthesis and potential coanthracyclinic activity of Imidazo[2,1-b]thiazole guanylhydrazones. Bioorg Med Chem 8:2359–2366
Andreani A, Granaiola M, Leoni A, Locatelli A, Morigi R, Rambaldi M, Lenaz G, Fato R, Bergamini C, Farruggia G (2005) Potential Antitumor Agents. 37.Synthesis and Antitumor Activity of Guanylhydrazones from Imidazo[2,1-b]thiazoles and from the New Heterocyclic System Thiazolo[2’,3’:2,3]imidazo[4,5-c]quinolone. J Med Chem 48:3085–3089
Ashwell M, Tandon M, Lapierre JM (2005) Preparation of pyrimidinyl imidazooxazoles and imidazothiazoles as inhibitors of p38 MAP kinase. PCT Pat. Appl. WO 2006044869
El-Subbagh HI, Al-Khawad IE, El-Bendary ER, Al-Obaid AM (2001) Substituted thiazoles. IV. Synthesis and antitumor activity of new substituted imidazo[2,1-b]thiazole analogs. Saudi Pharm J 9:14–20
Gürsoy E, Güzeldemirci NU (2007) Synthesis and primary cytotoxicity evaluation of new imidazo[2,1-b]thiazole derivatives. Eur J Med Chem 42:320–326
Park JH, Oh CH (2010) Synthesis of new 6-(4-fluorophenyl)-5-(2-substituted pyrimidin-4-yl)imidazo[2,1-b]thiazole derivatives and their antiproliferative activity against melanoma cell line. Bull Korean Chem Soc 31:2854–2860
Park JH, El-Gamal MI, Lee YS, Oh CH (2011) New imidazo[2,1-b]thiazole derivatives: synthesis, in vitro anticancer evaluation, and in silico studies. Eur J Med Chem 46:5769–5777
Srimanth K, Rao VR, Krishna DR (2002) Synthesis and evaluation of anticancer activity of some imidazothiazolyl, imidazobenzothiazolyl and dihydroimidazothiazolyl coumarins. Arzneimittelforschung 52:388–392
Townsend CA, Basak A (1991) Experiments and speculations on the role of oxidative cyclization chemistry in natural product biosynthesis. Tetrahedron 47:2591–2602
Tully DC, Liu H, Chatterjee AK, Alper PB, Epple R, Williams JA, Roberts MJ, Woodmansee DH, Masick BT, Tumanut C, Li J, Spraggon G, Hornsby M, Chang J, Tuntland T, Hollenbeck T, Gordon P, Harris JL, Karanewsky DS (2006) Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers. Bioorg Med Chem Lett 16:5112–5117
Acknowledgments
This work was supported by Korea Institute of Science and Technology (KIST), KIST Project (2E24680). We would like to thank the National Cancer Institute (NCI, Bethesda, Maryland, USA) for testing the antiproliferative activity of our target compounds over 55 cancer cell lines of nine different cancer types.
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Mohammed S. Abdel-Maksoud and Mohammed I. El-Gamal co-first authors.
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Abdel-Maksoud, M.S., El-Gamal, M.I., Gamal El-Din, M.M. et al. Broad-spectrum antiproliferative activity of a series of 6-(4-fluorophenyl)-5-(2-substituted pyrimidin-4-yl)imidazo[2,1-b]thiazole derivatives. Med Chem Res 25, 824–833 (2016). https://doi.org/10.1007/s00044-016-1529-7
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DOI: https://doi.org/10.1007/s00044-016-1529-7