Structural characterization and cytotoxicity studies of different forms of a combretastatin A4 analogue

Author(s)

de Figueiredo, Laysa P. ; Ibiapino, Amanda L. ; do Amaral, Daniel N. ; Ferraz, Leticia S. ; Rodrigues, Tiago ; Barreiro, Eliezer J. ; Lima, Lidia M. ; Ferreira, Fabio F.

• Document type: Journal article
• Source: Journal of Molecular Structure; v. 1147, p. 226-234, NOV 5 2017.
• Web of Science Citations: 3

Abstract

It is well known that combretastatin A4 (CA-4), which is a natural stilbene isolated from Combretum caffrum, is used to inhibit angiogenesis. However, depending on the dose administered to the patient, it can cause some side-effects. Herein, we present the synthesis and structural characterization of a novel N-acylhydrazone derivative - LASSBio-1735 - a CA-4 analogue. LASSBio-1735 has displayed in vitro antiproliferative activity against HL-60 (human leukemia), SF-295 (human glioblastoma), MDA-MB435 (melanoma) and HCT-8 (ileocecal adenocarcinoma) tumor cells. We found different hydration levels in two batches of the as-synthesized compound. As a consequence, we could successfully determine the crystal structures by using X-ray powder diffraction data and a simulated annealing procedure of the anhydrous and hydrated forms. The effects on cell viability of anhydrous and hydrated forms of LASSBio-1735 were comparatively evaluated in different tumor cell lines, and the hydrated form exhibited higher cytotoxicity in human leukemia K562 cells. These findings lead us to perform a quantitative phase analysis on one of the samples and may shed some light on the search for possible new solvates and/or hydrates. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 12/12247-8 - New applications of phenothiazines and Palladacycles: nanostructured systems to the mechanistic study of death in tumor cells
• Grantee: Tiago Rodrigues
• Support Opportunities: Regular Research Grants