Anticancer effects of O-aminoalkyl derivatives of alloxanthoxyletin and seselin.

Seselin and alloxanthoxyletin, naturally occurring pyranocoumarins, were recently isolated from a number of plant sources, such as family of Rutaceae. It was previously reported that their natural and synthetic derivatives show cytotoxic and antitumor activity. In the present study new series of O-aminoalkyl substituted alloxanthoxyletins and seselins were synthesized and evaluated for their anticancer toxicity. Microwave assisted synthesis was used, and the structures of the compounds were confirmed by 1H NMR, 13C NMR and MS spectroscopic data. The molecular and crystal structure of 3a was analyzed by single crystal X-ray diffraction. Alloxanthoxyletin derivatives 2a, 2b, and 2d showed the highest cytotoxic potential against HTB-140 cells with IC50 of 2.48, 2.80 and 2.98µM, respectively. In vitro drug sensitivity testing in HaCaT, A549 and HTB-140 cells were also performed. Tumor cells showed a higher sensitivity to tested compounds than normal cells. Compounds 2a, 2b and 2d inhibited cell migration and exerted stronger effect on A549 and HTB-140 cells than on HaCaT cells. In order to explain the basic mechanism of cell death induction we have investigated the effect of derivatives 2a, 2b and 2d on early and late apoptosis using annexin V-FITC/7-AAD flow cytometry analysis. Derivatives 2a and 2b were much more potent inducers of early apoptosis in HTB-140 cells compared to HaCaT and A549 cells.

1H-Tetrazol-5-amine and 1,3-thiazolidin-4-one derivatives containing 3-(trifluoromethyl)phenyl scaffold: Synthesis, cytotoxic and anti-HIV studies.

On the basis of recently reported biologically active 3-(trifluoromethyl)phenylthioureas, a series of diaryl derivatives incorporating 1H-tetrazol-5-yl (1a-11a, 1a'-11a') and 1,3-thiazolidin-4-one (1b-11b) scaffolds were synthesized. The synthesis pathway was confirmed by an X-ray crystallographic studies of 3a', 6a, 8a, 6b and 8b. The cytotoxicity against MT-4 cells and anti-HIV properties of new derivatives were evaluated. As compared to initial thiourea connections, the cyclisation reduced the cytotoxicity of compounds by 2-15 times. The most promising N-(4-nitrophenyl)-1H-tetrazol-5-amine 7a was found to be more active than the origin thiourea. Its cytotoxicity was evaluated on A549, HTB-140 and HaCaT cell lines using MTT assay. The compound shows significant influence on cancer, but not on normal cells. Obtained results can provide some constructive data for further designing of novel family of potentially bioactive analogs.

New thiourea and 1,3-thiazolidin-4-one derivatives effective on the HIV-1 virus.

Thiourea derivatives have been reported to possess many biological activities, among them antiviral and antitumoral properties. As part of our continuing effort to develop new active compounds, we report the synthesis and the evaluation of new fifteen thiourea derivatives with 1,3-benzothiazole-2-yl moiety, among them a group of biologically active (1-7) also underwent cyclization to 1,3-thiazolidin-4-ones. Molecular structure of four compounds (4, 13, 15 and 3a) was determined by an X-ray crystallography. We here report the evaluation of their cytotoxicity against human leukaemia/lymphoma- and solid tumour-derived cell lines and of their antiviral activity against HIV-1 and representatives of ssRNA and dsDNA viruses. Derivative 5 showed an interesting activity against HIV-1 wild type and against variants carrying clinically relevant mutations. A colorimetric enzyme immunoassay clarified its mode of action as a non-nucleoside inhibitor of the reverse transcriptase.