Ioannis K. Kostakis

Synthesis and free radical scavenging activity of some new spiropyranocoumarins

A series of novel spiro-substituted 4-hydroxypyranocoumarins and their corresponding dihydropyrano cis-diols has been synthesized. Among them the spiroadamantylpyranocoumarin and the diols can interact with the stable free radical 1,1-diphenyl-2-picrylhydrazyl and scavenge superoxide anions generated in the xanthine-xanthine oxidase system.

In vitro assessment of antioxidant activity of tyrosol, resveratrol and their acetylated derivatives.

Consumption of phenolic compounds is associated with beneficial effects in humans even though many of them are poorly absorbed. The aim of this study was to investigate the in vitro antioxidant activity of tyrosol (T), resveratrol (R) and their acetylated derivatives (AcD), as increased lipophilicity has been reported to improve absorption. The chemically synthesized AcDs were evaluated by their ability to scavenge DPPH radicals, inhibit non-enzymatic linoleic acid peroxidation, inhibit human serum oxidation in the presence of copper ions and inhibit lipoxygenase activity. T showed an inhibitory effect only in serum oxidation, where the T-acetylated at aromatic-OH was the most active. The T-acetylated at aliphatic-OH and 3,5-diacetyl-R exhibited the most powerful effect in non-enzymatic linoleic acid peroxidation with IC50 values 2.4 mM ± 0.21 and 0.055 mM ± 0.0018, respectively. In all other tests R was the most potent among all its AcD and T. Increasing lipophilicity by acetylation improves antioxidant activity of phenolic compounds in non-enzymatic lipid peroxidation assays.

Synthesis and cytotoxic activity of some new azapyranoxanthenone aminoderivatives.

A series of novel azapyranoxanthenones, bearing structural similarity to the acridone alkaloid acronycine have been designed and synthesized. Their in vitro cytotoxicities against the murine L1210 leukemia and the human solid tumor HT-29 cell lines have been investigated. The new derivatives exhibited interesting cytotoxic activity and were more potent than the parent compound.

Design and synthesis of some new pyranoxanthenone aminoderivatives with cytotoxic activity

The synthesis, DNA binding and in vitro cytotoxicity of a series of novel pyranoxanthones, analogues of the acridone alcaloid acronycine, are described. The new compounds proved to bind weakly to DNA. On the contrary, they exhibited interesting cytotoxic activity against murine leukemia L1210 cell line, as well as against some human solid tumor cell lines.

Synthesis, cytotoxic activity, NMR study and stereochemical effects of some new pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen-7-ones

Some new substituted pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen-7-ones were prepared and their cytotoxic activity was evaluated using acronycine as the reference compound. The conformation of the molecules was also investigated in an effort to correlate this parameter with the biological activity.

Synthesis and cytotoxic activity of 2-dialkylaminoethylamino substituted xanthenone and thioxanthenone derivatives

The synthesis and biological evaluation of some new pyranoxanthenones and pyranothioxanthenones, substituted with flexible amino side-chains, and their evaluation as potential antitumor agents is described. The cytotoxic activity of the compounds and their eventual selective effect on a phase of the cell cycle were evaluated in vitro, using the murine lymphocytic L1210 leukemia cell line. The new aminoderivatives exhibited highly potent cytotoxicity against the leukemia L1210 cell line when compared to acronycine. All the compounds induced a partial accumulation of cells in the G2 + M phase of the cell cycle.

Design, synthesis and cell growth inhibitory activity of a series of novel aminosubstituted xantheno[1,2-d]imidazoles in breast cancer cells.

A series of novel aminosubstituted xantheno[1,2-d]imidazole derivatives have been designed and synthesized and their antiproliferative activity has been evaluated against human breast MDA-MB-231 cell line. Among the tested compounds those bearing two basic side chains at 2- and 5-positions exhibited a strong dose-dependent antiproliferative activity. Increase of the size and basicity of the N-alkyl substituent resulted in amplification of the inhibitory activity.

Design, synthesis and antiproliferative activity of novel aminosubstituted benzothiopyranoisoindoles

The synthesis of a number of new benzothiopyrano[4,3,2-cd]isoindole aminoderivatives designed as structural analogues of the key metabolite of the anticancer agent Ledacrine (nitracrine) and their in vitro cytotoxic activity evaluation against HCT-116, MES-SA, and MES-SA/Dx cancer cell lines is reported. The majority of the derivatives possessed noticeable cytotoxicity in a low μM range indicating an interesting structure-activity relationship.

Platelet Activating Factor (PAF) biosynthesis is inhibited by phenolic compounds in U-937 cells under inflammatory conditions.

Interleukin 1 beta (IL-1β) induced platelet activating factor (PAF) synthesis in U-937 cells through stimulation of acetyl-CoA:lysoPAF-acetyltransferase (lyso PAF-AT) at 3 h and DTT-independentCDP-choline-1-alkyl-2-acetyl-sn-glycerol cholinophosphotransferase (PAF-CPT) at 0.5 h. The aim of this study was to investigate the effect of tyrosol (T), resveratrol (R) and their acetylated derivatives(AcDs) which exhibit enhanced bioavailability, on PAF synthesis in U-937 after IL-1β stimulation. The specific activity of PAF enzymes and intracellular levels were measured in cell homogenates. T and R concentration capable of inducing 50% inhibition in IL-1β effect on lyso PAF-AT was 48 μΜ ± 11 and 157 μΜ ± 77, for PAF-CPT 246 μΜ ± 61 and 294 μΜ ± 102, respectively. The same order of concentration was also observed on inhibiting PAF levels produced by IL-1β. T was more potent inhibitor than R (p<0.05). AcDs of T retain parent compound inhibitory activity, while in the case of R only two AcDs retain the activity. The observed inhibitory effect by T,R and their AcDs, may partly explain their already reported beneficial role.

The discovery of new cytotoxic pyrazolopyridine derivatives

A number of new 3,7-disubstituted pyrazolo[3,4-c]pyridines have been designed and synthesized from suitable 2-aminopyridines. The antiproliferative activity of the derivatives was determined against the pancreatic MIA PaCa-2 and ovarian SCOV3 cancer cell-lines. IC50 values of the most promising analogue 46 lie in the submicromolar or low micromolar range. Furthermore, compound 46 shows similar inhibitory activities against DU145, A2058 and PC-3 cancer cells, blocks the cell cycle at the G0/G1 phase and induce apoptosis, as determined by the appearance of apoptotic nuclei.