| Autor: |
Alexandre C. Bertoli, Hélio A. Duarte, Luciana B.P. Sâmia, Nivaldo L. Speziali, Heloisa Beraldo, Bárbara Kawamura, Gabrieli L. Parrilha, Adilson Kleber Ferreira, Sarah Fernandes Teixeira |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Journal of Molecular Structure. 1178:274-284 |
| ISSN: |
0022-2860 |
| DOI: |
10.1016/j.molstruc.2018.10.029 |
| Popis: |
4-[bis(2-chloroethyl)amino]benzaldehyde-N(4)-phenyl-thiosemicarbazone (1), 4-[bis(2-chloroethyl)amino]benzaldehyde-N(4)-para-chloro-phenyl-thiosemicarbazone (2), 4-[bis(2-chloroethyl)amino]benzaldehyde-N(4)-methyl-thiosemicarbazone (3) and 4-[bis(2-chloroethyl)amino]benzaldehyde-benzoylhydrazone (4) were obtained by functionalization of the bis(2-chloroethyl)amino DNA alkylating group with a thiosemicarbazone/hydrazone moiety. The compounds were fully characterized by means of their infrared (including theoretical vibrational analyses) and NMR spectra, as well as by means of X-ray crystal structure determinations. When assayed on a panel of different tumor cells only (1) exhibited cytotoxic effects on B16F10 melanoma cells (IC50 = 17.1 ± 3.1 μM). A cell viability assay on melanoma cells revealed that while (1) had cytotoxic effects on B16F10 and A2058 cells, the structure-related hydrazone (4) was devoid of activity. In addition, (1) was capable to reduce viability of melanoma cells without affecting the viability of non-malignant human endothelial cells (HUVEC), suggesting that this compound or its analogues could be further investigated as potential antimelanoma drug candidates. Preliminary investigation on the mode of action of (1) indicated that the compound induces cell death by necrosis. Theoretical calculations showed that in all compounds (1–4) the reactivities of the N-mustard pharmacophoric group towards dehalogenation are similar. In addition, theoretical studies suggested that the nucleophilicities of the mustard group are very similar in (1–4). Hence, all compounds (1–4) might be expected to exhibit comparable reactivity, and the differences in biological activity among the compounds may not be attributed to variances in reactivity at the N-mustard group. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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