(5<i>Z</i>)-3-(2-Oxopropyl)-5-(3,4,5-trimethoxybenzylidene)-1,3-thiazolidine-2,4-dione

Mague, Joel T.; Mohamed, Shaaban K.; Akkurt, Mehmet; El‐Kashef, Hussein; Lebegue, Nicolas; Albayati, Mustafa R.

doi:10.1107/s2414314616019593

Cited by 2 publications

(1 citation statement)

References 13 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The active methylene group of 1 was allowed to condense with 3,4,5-trimethoxybenzaldehyde via Knoevenagel reaction in boiling anhydrous toluene, in the presence of a catalytic amount of piperidinium acetate, using a Dean-Stark apparatus to produce the corresponding (Z)-5-(3,4,5-trimethoxybenzylidine)thiazolidine-2,4dione (2). The Z-conformation of the latter compound has been proven by x-ray analysis [49]. Treatment of compound 2 with ethanolic KOH solution gave the corresponding potassium salt 3 (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

Novel Thiazolidine-2,4-dione-trimethoxybenzene-thiazole Hybrids as Human Topoisomerases Inhibitors

et al. 2023

Self Cite

View full text Add to dashboard Cite

Cancer is a complex and heterogeneous disease and is still one of the leading causes of morbidity and mortality worldwide, mostly as the population ages. Despite the encouraging advances made over the years in chemotherapy, the development of new compounds for cancer treatments is an urgent priority. In recent years, the design and chemical synthesis of several innovative hybrid molecules, which bring different pharmacophores on the same scaffold, have attracted the interest of many researchers. Following this strategy, we designed and synthetized a series of new hybrid compounds that contain three pharmacophores, namely trimethoxybenzene, thiazolidinedione and thiazole, and tested their anticancer properties on two breast cancer (MCF-7 and MDA-MB-231) cell lines and one melanoma (A2058) cell line. The most active compounds were particularly effective against the MCF-7 cells and did not affect the viability of the normal MCF-10A cells. Docking simulations indicated the human Topoisomerases I and II (hTopos I and II) as possible targets of these compounds, the inhibitory activity of which was demonstrated by the mean of direct enzymatic assays. Particularly, compound 7e was proved to inhibit both the hTopo I and II, whereas compounds 7c,d blocked only the hTopo II. Finally, compound 7e was responsible for MCF-7 cell death by apoptosis. The reported results are promising for the further design and synthesis of other analogues potentially active as anticancer tools.

show abstract

Section: Chemistrymentioning

confidence: 99%

Novel Thiazolidine-2,4-dione-trimethoxybenzene-thiazole Hybrids as Human Topoisomerases Inhibitors

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

Synthesis of Nitrostyrylthiazolidine-2,4-dione Derivatives Displaying Antileishmanial Potential

Khoumeri,

Hutter,

Primas

et al. 2024

Pharmaceuticals

View full text Add to dashboard Cite

A series of 61 thiazolidine-2,4-diones bearing a styryl group at position 5 was synthesized in 2–5 steps and their structure was proved by elemental and spectral analyses. The compounds obtained were evaluated in vitro against the promastigote stage of the kinetoplastid parasite Leishmania infantum and the human HepG2 cell line, to determine selectivity indices and to compare their activities with those of antileishmanial reference drugs. The study of structure–activity relationships indicated the potential of some derivatives bearing a nitro group on the phenyl ring, especially when located at the meta position. Thus, among the tested series, compound 14c appeared as a hit compound with good antileishmanial activity (EC50 = 7 µM) and low cytotoxicity against both the hepatic HepG2 and macrophage THP-1 human cell lines (CC50 = 101 and 121 µM, respectively), leading to good selectivity indices (respectively, 14 and 17), in comparison with the reference antileishmanial drug compound miltefosine (EC50 = 3.3 µM, CC50 = 85 and 30 µM, SI = 26 and 9). Regarding its mechanism of action, among several possibilities, it was demonstrated that compound 14c is a prodrug bioactivated, predominantly by L. donovani nitroreductase 1, likely leading to the formation of cytotoxic metabolites that form covalent adducts in the parasite. Finally, compound 14c is lipophilic (measured CHI LogD7.7 = 2.85) but remains soluble in water (measured PBS solubility at pH7.4 = 16 µM), highlighting the antileishmanial potential of the nitrostyrylthiazolidine-2,4-dione scaffold.

show abstract

(5Z)-3-(2-Oxopropyl)-5-(3,4,5-trimethoxybenzylidene)-1,3-thiazolidine-2,4-dione

Cited by 2 publications

References 13 publications

Novel Thiazolidine-2,4-dione-trimethoxybenzene-thiazole Hybrids as Human Topoisomerases Inhibitors

Novel Thiazolidine-2,4-dione-trimethoxybenzene-thiazole Hybrids as Human Topoisomerases Inhibitors

Synthesis of Nitrostyrylthiazolidine-2,4-dione Derivatives Displaying Antileishmanial Potential

Contact Info

Product

Resources

About