Study on the Synthesis, Characterization and Bioactivities of 3-Methyl-9'-fluorenespiro-5-hydantoin.

This work describes a method for synthesis, as well as in vitro antiproliferative and antibacterial investigation of 3-methyl-9'-fluorenespiro-5-hydantoin. The structure of the substituted fluorenylspirohydantoin derivative was verified by UV-Vis, FT-IR, Raman, (1)H-NMR and (13)C-NMR spectroscopy, and by using a combination of 2D NMR experiments, which included (1)H-(1)H COSY, HMQC and HMBC sequences. The geometry of the compound was optimized by the B3LYP density functional with 6-31G(d) basis set and the (1)H and (13)C NMR spectra were predicted with the HF/6-31G(d) calculations at the optimized geometry. The anticancer activity of the 3-methyl-9'-fluorenespiro-5-hydantoin was determined in suspension cell lines originating from tumors in humans (WERI-Rb-1). The cytotoxic effect was evaluated by WST-assay (Roche Applied Science). The antimicrobial effect of the compound against Gram-negative, Gram-positive bacteria and the yeast Candida albicans was investigated.

New platinum(II) complexes of cycloalkanespiro-5-(2-thiohydantoins). Synthesis and quantum chemical investigation.

Synthesis and characterization of new Pt(II) complexes of cyclohexanespiro-5-(2-thiohydantoin) (L1) and cycloheptanespiro-5-(2-thiohydantoin) (L2) are discussed. The new complexes are studied by elemental analysis, IR, ATR FTIR spectroscopy. The free ligands are investigated by UV-Vis, FT-IR, (1)H NMR, (13)C NMR and Raman spectroscopy. The ground-state equilibrium geometries of the ligands L1 and L2 and their complexes with Pt(II) are optimized at the BLYP/CEP-31G theoretical level.

Synthesis of 3',4'-dihydro-2H,2'H,5H-spiro [imidazolidine-4,1'-naphthalene]-2,5-dione and its derivatives.

The synthesis of two novel compounds, 1-amino-3',4'-dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione and 1,3-bis(hydroxymethyl)-3',4'-dihydro-2H,2'H,5H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione, was reported. The structures of the compounds were verified by (1)H, (13)C NMR and IR spectroscopy and quantum-chemical calculations at DFT level.

Synthesis and in vitro activity of platinum(II) complexes of two fluorenylspirohydantoins against a human tumour cell line.

This paper presents a method for synthesis and cytotoxicity of new platinum(II) complexes of (9'-fluorene)-spiro-5-hydantoin (L1) and (9'-fluorene)-spiro-5-(2-thiohydantoin) (L2). The new obtained complexes were studied by elemental analysis: ultraviolet-visible, attenuated total reflection Fourier transform infrared (ATR-FTIR), and 1H- and 13C-NMR for Pt(II) compounds and additionally Raman spectroscopy for free ligands. Based on the experimental data, the most probable structure of the complexes is suggested. In the present study, we have examined cytotoxic activity of (9'-fluorene)-spiro-5-hydantoin (L1) and (9'-fluorene)-spiro-5-(2-thiohydantoin) (L2) and their Pt(II) complexes on the retinoblastoma cell line WERI-Rb-1.

Two methods for spirothiohydantoin synthesis.

Two methods for spirothiohydantoin synthesis are presented. The title compounds were prepared with reaction of the corresponding 1-aminocycloalkanecarboxylic acids and thiourea. These compounds were also prepared by a hydrolysis of the relevant spirodithiohydantoins with barium hydroxide. The structures of the compounds obtained were verified by comparison of 1H, and 13C NMR, IR and MS spectral data.

Synthesis, Characterization, Quantum-Chemical Calculations and Cytotoxic Activity of 1,8-Naphthalimide Derivatives with Non-Protein Amino Acids.

BACKGROUND: The 1,8-Naphthalimides constitute an important class of biologically active, DNAbinding compounds. There are no available data on the synthesis of 1,8-naphthalimide derivatives with nonprotein amino acids and their biological activity. The aim of this paper was to determine the synthesis, structural characterization and cytotoxic activity of new 1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)cycloalkane-1- carboxylic acids with 5-, 6-, 7-, 8- and 12-membered rings as well as 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)- yl)adamantane-2-carboxylic acid and 1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-1,2,3,4-tetrahydronaphthalene- 1-carboxylic acid. METHODS: The target compounds were obtained by an interaction of 1,8-naphthalic anhydride with a series of non-protein amino acids. The optimized geometry and harmonic vibrational frequencies have been calculated by DFT employing B3LYP functional using 6-31G(d,p) basis set. An ab initio (MP2 and Hartee-Fock) and DFT (different functionals) using several basis sets have been applied for NMR calculations. The cytotoxic effects of the synthesized compounds are assessed against two human tumor cell lines, namely K-562 (chronic myeloid leukemia) and HUT-78 (cutaneous T-cell lymphoma) after 72 h exposure, using the MTT-dye reduction assay. The apoptogenic effects and the ability to modulate the NFκB-signaling pathways were determined using commercially available ELISA kits. RESULTS: All compounds inhibited the growth of malignant cells at micromolar concentrations whereby compound 4b (1-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)cyclohexane-1-carboxylic acid) demonstrated superior activity in both cell lines with IC50 values comparable to those of the reference anticancer drug melphalan. CONCLUSION: New 1,8-naphthalimide derivatives with non-protein amino acids were successfully synthesized. Quantum-chemical calculations were performed to elucidate the structure of the newly synthesized compounds. There is a proper alignment between theoretical and experimental results. The cytotoxicity of the synthesized products against two human tumor cell lines, namely K-562 and HUT-78 was evaluated. All compounds inhibited the growth of malignant cells at micromolar concentrations. The pharmacodynamics evaluation of compound 4b showed that its cytotoxicity is mediated by induction of apoptosis and inhibition of NFκB-signaling.

Aminoderivatives of cycloalkanespirohydantoins: synthesis and biological activity.

3-Aminocycloalkanespiro-5-hydantoins were synthesized and their biological activity was studied. In contrast to hydantoins, these compounds failed to induce either anticonvulsive effects in the central nervous system or inhibitory effects on cholinergic contractions in the enteric nervous system. However, they exerted well pronounced, atropinsensitive, contractile effects on the guinea-pig ileum longitudinal muscle preparations. Structure-activity relationships established allow the assumption that: (i) the reduction of the ring size in the molecule of the spirohydantoins leads to an increase in the potency of the respective analogue to induce contractile effect; (ii) the introduction of -NH2 in position 3 increases the ability of all the compounds studied to exert contractions; (iii) the enlargement of the ring leads to: (1) an increase of the degree of desensitization of the preparations; and (2) a decrease (except 1a) of the potency of the analogues to exert contractile effects.

A complete 1H and 13C NMR data assignment for 3-phenylmethylene-1H,3H-naphtho-[1,8-c,d]-pyran-1-one.

Complete assignments of the 1H and 13C NMR chemical shifts for 3-phenylmethylene-1H,3H-naphtho-[1,8-c,d]-pyran-1-one were done by means of one- and two-dimensional NMR techniques, including 1H-(1)H COSY, HMQC and HMBC spectra. Ab initio quantum chemistry calculations and a shift prediction by an incremental method provided values close to the proposed assignments. All mid-IR spectral bands are given as reference data. The DRIFT FTIR, ATR FTIR and Raman spectra are given as a Supplementary data in JCAMP-DX format, version 4.24. In addition, a method of compound's synthesis, that has the product yield higher as compared to already known data in the literature, is given.