Design, synthesis, and biological evaluation of simplified tetrahydroisoquinoline analogs.

A series of tetrahydroisoquinoline derivatives were prepared and their antitumor activity was studied against several human carcinoma cell lines, including Ketr3, BEL-7402, BGC-823, KB, HCT-8, MCF-7, HeLa, A2780, A549, and HT-1080. Compound 20, an analog of phthalascidin 650, exhibited good broad-spectrum antitumor activity in vitro. However, compounds 19 and 21, in which the side chains at C-22 are simplified, showed no obvious antitumor activity, indicating that the C-22 side chain of this type of compound has a greater impact on its activity. The difference in the in vivo activity between compound 20 and phthalascidin 650 also shows a significant effect of the substituents on the skeleton structure on the in vivo activity.

Novel Coumarin-furo[2,3-d]pyrimidinone hybrid derivatives as anticancer agents: Synthesis, biological evaluation and molecular docking.

A series of coumarin-furo[2,3-d]pyrimidinone hybrid derivatives were synthesized, characterized by HR-MS, 1H NMR and 13C NMR. All synthesized compounds were evaluated for antiproliferative activities against hepatic carcinoma (HepG2) and cervical carcinoma (Hela) cell lines in vitro, and results shown that most of the compounds exhibited potent antitumor activity. Moreover, compound 3i, 8d and 8i were selected to induce apoptosis in HepG2 cells, and it displayed a significant concentration-dependent. Further, transwell migration assay was used to detect the most potent compound 8i, and the results revealed that 8i can significantly inhibit HepG2 cells migration and invasion. In addition, kinase activity assay showed compound 8i may be a multi-target inhibitor, which 8i has an inhibition rate of 40-20% on RON, ABL, GSK3α and so on ten different kinases at the concentration 1 µmol/L. At the same time, molecular docking studies revealed the possible binding modes of compounds 3i, 8d and 8i with kinase recepteur d'origine nantais (RON). A comparative molecular field analysis (CoMFA) model was established from 3D-QSAR study that guide us to a more bulkly and electro-positive Y group at the C-2 position of furo[2,3-d]pyrimidinone ring was preferable for the bioactivity improvement of our compounds. Our preliminary research indicated that the coumarin skeleton introducing to the furo[2,3-d]pyrimidine system had a significantly influence on the biological activities.

Stimuli-responsive nanocarrier delivery systems for Pt-based antitumor complexes: a review.

Platinum-based anticancer drugs play a crucial role in the clinical treatment of various cancers. However, the application of platinum-based drugs is heavily restricted by their severe toxicity and drug resistance/cross resistance. Various drug delivery systems have been developed to overcome these limitations of platinum-based chemotherapy. Stimuli-responsive nanocarrier drug delivery systems as one of the most promising strategies attract more attention. And huge progress in stimuli-responsive nanocarrier delivery systems of platinum-based drugs has been made. In these systems, a variety of triggers including endogenous and extracorporeal stimuli have been employed. Endogenous stimuli mainly include pH-, thermo-, enzyme- and redox-responsive nanocarriers. Extracorporeal stimuli include light-, magnetic field- and ultrasound responsive nanocarriers. In this review, we present the recent advances in stimuli-responsive drug delivery systems with different nanocarriers for improving the efficacy and reducing the side effects of platinum-based anticancer drugs.

Conductive polymer sorbent for extraction and determination of resveratrol and polydatin in Polygonum cuspidatum root samples.

INTRODUCTION: The quantitative analysis of trace resveratrol and polydatin in plant tissues is suitable for elucidation of the compounds' mechanisms of action. OBJECTIVES: The main objective of this work was to develop a feasible and effective sample pretreatment method to measure the concentrations of resveratrol and polydatin in complex samples. METHODOLOGY: A polymer sorbent, poly(2-mercaptobenzimidazole), was electrochemically prepared and utilized for selective extraction, while resveratrol and polydatin were used as target analytes. The sorbent was characterized by cyclic voltammetry, scanning electron microscopy and Fourier transform infrared spectroscopy. After extraction and elution, the analytes were analyzed by a Thermo U3000 HPLC system. Several affecting parameters, including the volume of elution solution, sample pH value, sample flow rate and sample volume, were evaluated and optimized. RESULTS: The proposed method showed good linearity with low limits of detection (from 0.5 to 0.8 ng·mL-1 ) and ideal accuracy with spiked recoveries from 81.30% to 99.16%. A good enrichment factor (more than 200-fold) together with good sensitivity was obtained with this method. Analysis of resveratrol and polydatin in Polygonum cuspidatum samples by this method is efficient. CONCLUSION: The method developed in this work exhibits several significant merits, including easy operation and high extraction efficiency, indicating that electrochemically prepared polymer sorbent is useful for sample pretreatment and analysis of traditional Chinese medicine samples.

Synthesis and Discovery of Schiff Base Bearing Furopyrimidinone for Selective Recognition of Zn2+ and its Applications in Cell Imaging and Detection of Cu2.

A simplefuro [2,3-d]pyrimidinone-based Schiff base FPS was synthesized via aza-Wittig reaction and structure elucidation was carried out by spectroscopic studies FT-IR, 1H NMR, and 13C NMR and mass spectrometry. FPS showed weak fluorescence emission in methanol and the selectivity of FPS to different metal ions (Mn2+, Ca2+, Fe2+, Fe3+, Mg2+, Al3+, Ba2+, Ag+, Co2+, Na+, K+, Cu2+, Zn2+, Pb2+, Bi3+) were studied by absorption and fluorescence titration. The results show that FPS has selective fluorescence sensing behavior for Zn2+ ions and the limit of detection (LOD) was calculated to be 1.19 × 10-8 mol/L. Moreover, FPS-Zn2+ acts as a metal based highly selective and sensitive new chemosensor for Cu2+ ions and the LOD was calculated to be 2.25 × 10-7 mol/L. In accordance with the results and theoretical calculations, we suspected that the binding mechanisms of FPS to Zn2+ and Cu2+ were assigned to be the cooperative interaction of Zn2+(Cu2+)-N.

3,3'-(1,4-Phenyl-ene)bis-[2-(propyl-amino)-benzofuro[3,2-d]pyrimidin-4(3H)-one] ethanol disolvate.

The title compound, C(32)H(28)N(6)O(4)·2C(2)H(5)OH, consists of two 2-(propyl-amino)-benzofuro[3,2-d]pyrimidin-4(3H)-one units connected, via one of the pyrimidine N atoms, to a bridging benzene ring in the 1,4 positions. Two ethanol solvent mol-ecules are also present. The main mol-ecule lies on a center of symmetry located at the center of the benzene ring. The fused-ring system of the benzofuro[3,2-d]pyrimidine moiety is nearly planar (r.m.s. deviation = 0.016 Å) and forms a dihedral angle of 78.21 (7)° with the central benzene ring. The crystal structure features O-H⋯O and N-H⋯O inter-actions. The C atoms of the propyl-amino side chain in the main mol-ecule and the ethyl group in the solvent mol-ecule are disordered over two positions, with site-occupancy factors 0.34:0.66 and 0.42:0.58, respectively.

Ethyl 2-diethyl-amino-4-oxo-3,5-diphenyl-4,5-dihydro-3H-pyrrolo-[3,2-d]pyrimidine-7-carboxyl-ate.

In the title compound, C(25)H(26)N(4)O(3), the two fused pyrrolo-[3,2-d]pyrimidine rings form a dihedral angle of 3.7 (2)°. The two substituent phenyl rings are twisted with respect to the pyrrole and pyrimidine rings, making dihedral angles of 57.2 (2) and 69.0 (2)°, respectively. The ethyl and eth-oxy groups are disordered over two positions; the site occupancies are 0.53 (1) and 0.47 (1) for ethyl, and 0.63 (1) and 0.37 (1) for eth-oxy. The crystal packing features C-H⋯O hydrogen bonds.

Efficient synthesis and biological evaluation of some 2,4-diamino-furo[2,3-d]pyrimidine derivatives.

The carbodiimides 2, obtained from aza-Wittig reactions of iminophosphorane 1 with aromatic isocyanates, reacted with ammonia to give ethyl 3,4-dihydro-6-methyl-4-oxo-2-arylamino-furo[2,3-d]pyrimidine-5-carboxylate 3. Further reaction of 3 with POCl(3) and various amines generated ethyl 4-alkylamino-2-arylamino-6-methyl-furo[2,3-d]pyrimidine-5-carboxylate 5 in good yields. Their structures were confirmed by (1)H NMR, EI-Ms, IR and elemental analysis. Compound 5b was further analyzed by single crystal X-ray diffraction. Compound 5 exhibited cytotoxicity against two lung cancer cell lines. For example, compound 5a showed the best inhibition activities against A459 with IC(50) 0.8µM.

3-(4-Fluoro-phen-yl)-2-(2-naphth-yloxy)-4-oxo-5-phenyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-7-carbonitrile.

The title compound, C(29)H(17)FN(4)O(2), may be used as a new precursor for obtaining bioactive mol-ecules. There are two crystallographically independent mol-ecules in the asymmetric unit. The phenyl ring, 4-fluoro-phenyl ring and 2-naphth-yloxy ring are twisted with respect to the pyrrolopyrimidine ring by 52.30 (11)/49.05 (11), 80.94 (10)/88.36 (10) and 60.58 (7)/83.76 (7)°, respectively. The crystal packing is stabilized by weak C-H⋯N hydrogen bonds.

2-(Dibutyl-amino)-3-(4-fluoro-phen-yl)-5,6,7,8-tetra-hydro-7-methyl-6,8-di-phenyl-pyridine-[3',4':2,3]thieno[5,4-d]pyrimidin-4(3H)-one.

In the crystal structure of the title compound, C(36)H(39)FN(4)OS, the two fused rings of the thienopyrimidine system are coplanar. The 4-fluoro-phenyl ring is twisted with respect to the heterocyclic pyrimidinone ring by 67.21 (14)°. The piperidine ring shows a half-chair conformation. One of the n-butyl chains is disordered equally over two sites. The crystal packing is stabilized by C-H⋯O hydrogen bonds.

A facile synthesis and fungicidal activities of 2-(alkylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones.

The aza-Wittig reactions of iminophosphorane 3 with aromatic isocyanates generated carbodiimides 4, which were reacted with alkylamines under mild conditions to give a series of 2-(alkylamino)-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones 6 and 8 in satisfactory yield. Their structures were confirmed by (1)H NMR, EI-MS, IR and elementary analysis, and compound 8c was further analyzed by single-crystal X-ray diffraction. The preliminary bioassays indicated that these compounds showed excellent fungicidal activities against six kinds of fungi.

3-Phenyl-2-(prop-2-yn-yloxy)-1-benzofuro[3,2-d]pyrimidin-4(3H)-one.

In the title compound, C(19)H(12)N(2)O(3), the 1-benzofuro[3,2-d]pyrimidinone unit is approximately planar, the maximum deviation from the mean plane being 0.045 (1) Å. The attached phenyl ring makes a dihedral angle of 86.73 (6)° with the fused ring system. The packing of the mol-ecules in the crystal structure is mainly governed by C-H⋯π hydrogen-bonding inter-actions.

Ethyl 3-(4-fluoro-phen-yl)-6-methyl-4-oxo-2-(1-cyclohexylamino)-3,4-dihydro-furo[2,3-d]pyrimidine-5-carboxyl-ate.

In the crystal structure of the title compound, C(22)H(24)FN(3)O(4), the two fused rings of furo[2,3-d]pyrimidine form a dihedral angle of 0.88 (13)°. The attached benzene ring is twisted with respect to the heterocyclic pyrimidinone ring, making a dihedral angle of 75.07 (12)°. The cyclo-hexyl ring shows a distorted chair conformation. The mol-ecular structure is stabilized by intra-molecular C-H⋯O and C-H⋯N hydrogen-bonding inter-actions. The crystal packing is mainly stabilized by C-H⋯π hydrogen-bond inter-actions. Further stability is provided by C-F⋯π and C-O⋯π stacking inter-actions.

Ethyl 2-[1-(4-chloro-phen-yl)-2,5-dioxo-1,2,3,5-tetra-hydro-imidazo[1',2':1,2]pyrimidino[5,4-b][1]benzofuran-3-yl]acetate.

The asymmetric unit of the title compound, C(22)H(16)ClN(3)O(5), consists of two crystallographically independent mol-ecules. The fused rings of the imidazo[1,2-a]benzo[4,5]furo[3,2-d]pyrimidine system are nearly coplanar and the chlorophenyl rings are twisted with respect to the two pyrimidinone ring systems by 71.00 (2) and 62.59 (2)°. The C atoms of the ethyl side chain are disordered and were refined using a split model. In the crystal structure, the mol-ecules are connected via weak intra- and inter-molecular C-H⋯O inter-actions are present. The ethyl group in one molecule is disordered over two positions, with site occupancy factors 0.55 and 0.45; in the other molecule only the methyl group is disordered over two positions, with site occupancy factors 0.6 and 0.4.