Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

Open access


Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

1. F. P. Schmidtchen and M. Berger, Artificial organic host molecules for anions, Chem. Rev. 97 (1997) 1609–1646; DOI: 10.1021/cr9603845.

2. U. E. W. Lange, D. Baucke, W. Hornberger, H. Mack, W. Seitz and H. W. Höffken, D-Phe-Pro-Arg type thrombin inhibitors: unexpected selectivity by modification of the P1 moiety, Bioorg. Med. Chem. Lett. 13 (2003) 2029–2033; DOI: 10.1016/S0960-894X(03)00347-0.

3. J. L. Jiménez Blanco, P. Bootello, J. M. Benito, C. O. Mellet and J. M. García Fernandez, Urea-, thiourea-, and guanidine-linked glycooligomers as phosphate binders in water, J. Org. Chem. 71 (2006) 5136–5143; DOI: 10.1021/jo060360q.

4. S. Ekelund, P. Nygren and R. Larsson, Guanidino-containing drugs in cancer chemotherapy: biochemical and clinical pharmacology, Biochem. Pharmacol. 61 (2001) 1183–1193; DOI: 10.1016/S0006-2952(01)00570-6.

5. A. Andreani, M. Granaiola, A. Leoni, A. Locatelli, R. Morigi, M. Rambaldi, G. Lenaz, R. Fato, C. Bergamini and G. Farruggia, 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]quinoline, J. Med. Chem. 48 (2005) 3085–3089; DOI: 10.1021/jm040888s.

6. A. L. LaFrate, J. R. Gunther, K. E. Carlson and J. A. Katzenellenbogen, Synthesis and biological evaluation of guanylhydrazone coactivator binding inhibitors for the estrogen receptor, Bioorg. Med. Chem. 16 (2008) 10075–10084; DOI: 10.1016/j.bmc.2008.10.007.

7. P. Ulrich and A. Cerami, Trypanocidal 1,3-arylene diketone bis(guanylhydrazone)s. Structure-activity relationships among substituted and heterocyclic analogues, J. Med. Chem. 27 (1984) 35–40; DOI: 10.1021/jm00367a007.

8. J. R. Ring, F. Zheng, A. J. Haubner, J. M. Littleton and P. A Crooks, Improving the inhibitory activity of arylidenaminoguanidine compounds at the N-methyl-D-aspartate receptor complex from a recursive computational-experimental structure-activity relationship study, Bioorg. Med. Chem. 21 (2013) 1764–1774; DOI: 10.1016/j.bmc.2013.01.051.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information

IMPACT FACTOR 2017: 1.071
5-year IMPACT FACTOR: 1.623

CiteScore 2017: 1.46

SCImago Journal Rank (SJR) 2017: 0.362
Source Normalized Impact per Paper (SNIP) 2017: 0.642

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 217 217 18
PDF Downloads 94 94 12