Design, synthesis and neuraminidase inhibitory activity of 4-methyl-5-(3-phenylacryloyl) thiazoles.

A series of 4-methyl-5-(3-phenylacryloyl)thiazoles based on chalcones were designed, synthesized and evaluated for their influenza neuraminidase (NA) inhibitory activity in vitro. A preliminary structure-activity relationship (SAR) analysis showed that thiazoles bearing amide had greater potency. It also showed that mono-hydroxyl group at 4-position on phenyl ring was more effective than other electron-releasing groups or electron-withdraw groups. Compounds A2 and A26 were more potent against NA with IC50 values of 8.2 ± 0.5 µg/mL and 6.2 ± 1.4 µg/mL, respectively. Molecular docking study demonstrated that thiazoles skeleton was benefit for the NA inhibitory activity.

Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors.

Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC50 values of 12.77 ± 0.47 and 12.96 ± 1.34 µg/ml, respectively. On the basis of the biological results, a preliminary structure-activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.

Design, synthesis and biological evaluation of honokiol derivatives as influenza neuraminidase inhibitors.

Honokiol, a natural polyphenol, which was reported to have satisfactory influenza neuraminidase (NA) inhibitory activity, was structurally modified. Twenty-three compounds were synthesized and the ortho-effects in the epoxidation and hydrolyzation reactions were studied. The derivatives were evaluated for NA inhibitory activity and the benzoylhydrazone derivatives showed much better anti-NA activity than honokiol. Structure-activity relationship analysis suggested that the polyphenols exhibited better anti-NA activity than monophenols and biphenols. Furthermore, probable binding mode of drug with target revealed that the most active compound had much stronger interactions with the active site of NA than honokiol suggesting the potent anti-influenza virus activity.

One-Pot Three-Component Synthesis of Novel Diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(arylamino)methyl)phosphonate as Potential Anticancer Agents.

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.

Design, Synthesis, and Antitumor Activity of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones.

A series of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones (C1-C35) were designed and synthesized, and the structures of compounds (Z)-C27 and (Z)-C29 were confirmed by single-crystal X-ray diffraction. The antitumor activities of these novel compounds against cervical cancer (HeLa), lung cancer (A549), and breast cancer (MCF-7) cell lines were evaluated in vitro. Majority of the title compounds exhibited strong antitumor activities and were much more promising than the positive control Taxol, which were also accompanied by lower cytotoxicity to normal cells. In particular, compounds (E,Z)-C24 exhibited the most consistent potent activities against three neoplastic cells with IC50 values ranging from 3.2 to 7.1 µm. Further researches demonstrated that compounds (E,Z)-C24 could induce cell apoptosis and arrest cell cycle at the G2/M and S phases. Meanwhile, the structure-activity relationship between the configurations and cytotoxicity of the compounds was also investigated.

Bis(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl) carbonate.

The title compound, C(21)H(22)O(5), crystallizes with three mol-ecules in the asymmetric unit. In one mol-ecule, two methyl groups are disordered over two positions with a site occupation factor of 0.72 (2) for the major occupancy site. The benzene rings make dihedral angles of 35.3 (6), 29.7 (6) and 40.6 (7)° in the three molecules.

2-(2,2-Dimethyl-2,3-dihydro-1-benzofuran-7-yl-oxy)acetic acid monohydrate.

In the title compound, C(12)H(14)O(4)·H(2)O, the dihydro-benzo-furan ring adopts an envelope conformation with the substituted C atom 0.142 (1) Šout of the least-squares plane. In the crystal, the components are linked via inter-molecular O(water)-H⋯O and O-H⋯O(water) hydrogen-bonding inter-actions, forming a three-dimensional network.

2-(2,2-Dimethyl-2,3-dihydro-1-benzofuran-7-yl-oxy)-N-(o-tol-yl)acetamide.

In the title compound, C(19)H(21)NO(3), the dihedral angle between the mean planes of the two benzene rings is 38.13 (12)°. The furan ring adopts an envelope-like conformation with the C atom bonded to the dimethyl groups displaced by 0.356 (2) Šfrom the plane through the other four atoms. In the crystal, mol-ecules are linked into inversion dimers by weak C-H⋯O inter-molecular inter-actions.

2,2,7,7-Tetra-methyl-2,3,6,7-tetra-hydro-benzofuro[7,6-b]furan.

The title compound, C(14)H(18)O(2), was obtained as a by-product during the preparation of carbofuran phenol. The two dihydro-furan rings are in envelope conformations.

2-Amino-4-tert-butyl-5-(2,4-dichloro-benz-yl)thia-zol-3-ium bromide.

The asymmetric unit of the title compound, C(14)H(17)Cl(2)N(2)S(+)·Br(-), contains one cation and two Br(-) ions with site symmetry . The dihedral angle between the planes of the thia-zol and the dichloro-phenyl rings is 77.8 (6)°. In the crystal, the ions are connected by N-H⋯Br hydrogen bonds.

2-Amino-4-tert-butyl-5-(4-chloro-benz-yl)thia-zol-3-ium chloride.

The title compound, C(14)H(18)ClN(2)S(+)·Cl(-), crystallizes with two formula units in the asymmetric unit. The dihedral angles between the mean planes of the chloro-phenyl and thia-zole rings are 87.8 (2) and 88.0 (2)° in the two independent mol-ecules. In the crystal, the anions and cations are connected by N-H⋯Cl hydrogen bonds.

2-[4-tert-Butyl-5-(2-chloro-benz-yl)-1,3-thia-zol-2-yl]isoindoline-1,3-dione.

In the title compound, C(22)H(19)ClN(2)O(2)S, the dihedral angle between the phenyl-ene ring and the phthalimide ring system is 4.4 (1)°. There is no hydrogen bonding or π-π stacking in the crystal structure.

2-(2-Amino-5-methylthia-zol-4-yl)phenol.

In the title compound, C(10)H(10)N(2)OS, the benzene ring is nearly co-planar with the thia-zole ring, making a dihedral angle of 2.1 (2)°. The crystal structure is stabilized by inter-molecular N-H⋯O hydrogen bonds. An intra-molecular O-H⋯N hydrogen bond is also present.

2-Ethyl-6-methyl-anilinium 4-methyl-benzene-sulfonate.

The title compound, C(9)H(14)N(+)·C(7)H(7)SO(3) (-), contains a 2-ethyl-6-methyl-anilinium cation and a 4-methyl-benzene-sulfonic anion. The cations are anchored between the anions through N-H⋯O hydrogen bonds. Electrostatic and van der Waals inter-actions, as well as hydrogen bonds, maintain the structural cohesion.

1-(4-Chloro-phen-yl)-4,4-dimethyl-pent-1-en-3-one.

In the title compound, C(13)H(15)ClO, the carbonyl and ethenyl groups are not coplanar with benzene ring system, forming dihedral angles of 35.37 (5) and 36.27 (11)°, respectively. The mol-ecules are packed in an offset face-to-face arrangement showing π-π stacking inter-actions involving the benzene rings [centroid-centroid distance = 3.586 (4) Å].

8-Chloro-2-methyl-quinoline.

In the title compound, C(10)H(8)ClN, the crystal packing shows π-π stacking between the heterocyclic ring and the aromatic ring, with a centroid-centroid distance of 3.819 Å. The crystal studied was a racemic twin, the ratio of the twin components being 0.65 (7):0.35 (7).

8-Bromo-2-methyl-quinoline.

In the crystal structure of the title compound, C(10)H(8)BrN, the dihedral angle between the two six-membered rings of the quinoline system is 0.49 (16)°. The mol-ecules are packed in a face-to-face arrangement fashion, with a centroid-centroid distance of 3.76 Šbetween the benzene and pyridine rings of adjacent mol-ecules. No hydrogen bonding is found in the crystal structure.

4,4-Dimethyl-1-(3-nitro-phen-yl)pent-1-en-3-one.

All the non-hydrogen atoms except one methyl C atom of the title compound, C(13)H(15)NO(3), lie on a crystallographic mirror plane perpendicular to the b axis. The crystal packing is stabilized by two weak inter-molecular C-H⋯O hydrogen bonds.

2-Bromo-4,4-dimethyl-1-(2,4,5-trimethoxy-phen-yl)pentan-3-one.

The three meth-oxy groups of the title compound, C(16)H(23)BrO(4), are almost coplanar with the attached aromatic ring, forming dihedral angles of 7.19 (13), 2.48 (13) and 7.24 (12)°. The crystal structure shows an intra-molecular and an inter-molecular C-H⋯O inter-action.

4-tert-Butyl-5-(1H-1,2,4-triazol-1-yl)thia-zol-2-amine.

The dihedral angle between the triazole ring and the thia-zole ring in the title compound, C(9)H(13)N(5)S, is 64.35 (7)°. The crystal structure is stabilized by inter-molecular N-H⋯N hydrogen bonds, which link the mol-ecules into a two-dimensional network.