High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes

Abstract

Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a–1c and 3-hydroxy-4-thiopyridones 1d–1f as well as their Ru(η6-p-cymene)Cl complexes 2a–2f, and report here the molecular structures of 1b and 1d as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones 1d–1f, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low μM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells.

Ruthenium Complexes: An Alternative to Platinum Drugs in Colorectal Cancer Treatment

“…Moreover, some Ru-complexes were reported to be more effective compared to the conventional chemotherapeutic drug (5-FLU) which has been used as first-line treatment against CRC. Though Ru conjugation with organic molecules could enhance anticancer activity through a synergistic effect [ 82 , 83 , 84 ], sometimes Ru-complexes are found to be less potent compared to parent organic molecules against CRC cells [ 90 , 222 ]. While conjugation of Ru-compounds with RuNps enhanced cellular uptake, selectivity, and drug delivery in CRC cells.…”

Ru(ii)arene(N^N bpy/phen)-based RAPTA complexes for in vitro anti-tumour activity in human glioblastoma cancer cell lines and in vivo toxicity studies in a zebrafish model

“…In order to accomplish this study, cells were maintained for 72 h with complexes of various concentrations ranging from 2-160 mM, taking cisplatin as a typical positive control. 22 All these complexes exhibited signicant potency against the aforementioned cell lines representing the IC 50 value comparable to cisplatin. Complexes 4c and 4d displayed the best potency against all the brain cancer cells (Fig.…”

“…In vitro cytotoxic activities (MTT assay). 22 RAPTA complexes were dissolved in 1% DMSO, and 0.9% NaCl aqueous solution was used to dissolve cisplatin. A cell suspension was prepared and the number of cells taken was 2.5 Â 10 4 mL À1 .…”

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies

“…The anticancer agents with poor selectivity destroy cancer and normal cells, thereby posing adverse effects that limit the efficacy and safety of treatment [144]. Calculation of a selectivity index helps to understand the selectivity of an anticancer agent [184]. The selectivity of some GNMs toward HMs could not be calculated from some of the reported studies, as experimentation was conducted only against the cancer cells.…”