Discovery of Novel Allopurinol Derivatives with Anticancer Activity and Attenuated Xanthine Oxidase Inhibition.

A series of pyrazolo[3,4-d]pyrimidine derivatives related to allopurinol has been synthesized and evaluated for its cytotoxicity against a panel of three cancer cell lines as well as its xanthine oxidase (XOD) inhibitory activities. Among them, compound 4 showed potent cytotoxicity with IC50 values of 25.5 and 35.2 µM against human hepatoma carcinoma cell lines, BEL-7402 and SMMC-7221, respectively. The anticancer activity of 4 was comparable to that of Tanespimycin (17-N-allylamino-17-demethoxy geldanamycin, 17-AAG) that inhibited the growth of BEL-7402 and SMMC-7221 cells at IC50 values of 12.4 and 9.85 µM, respectively. However, unlike allopurinol, which is also a strong inhibitor of XOD, compound 4 is a much weaker XOD inhibitor, suggesting that the anticancer activities of the allopurinol derivatives may not be associated with XOD inhibition. Moreover, the cytotoxicity of 4 toward normal cells is significantly lower than that of 17-AAG, making 4 a promising lead compound for further optimization of structure-activity relationships that may lead to anticancer agents of clinical utility.

Synthesis and antigastric ulcer activity of novel 5-isoproyl-3,8-dimethylazulene derivatives.

5-Isoproyl-3,8-dimethylazulene derivatives were synthesized and evaluated for antigastric ulcer activity in vivo. Some of them possess the best activity against gastric ulcer with ulcer index values lower than the drug reference (omeprazole). The structure-activity relationship (SAR) shows that the lipophilic flat structure contributes to quite potent antigastric ulcer activity.

(E)-1-(4-Chloro-phen-yl)-3-[4-(2,3,4,6-tetra-O-acetyl-ß-d-allopyranos-yloxy)phen-yl]prop-2-en-1-one.

The asymmetric unit of the title compound, C(29)H(29)ClO(11), contains two independent mol-ecules of similar geometry, both adopting an E conformation about the C=C double bond. The dihedral angles formed by benzene rings are 10.73 (16) and 13.79 (18)°. The pyran-oside rings adopt a chair conformation. Intra-molecular C-H⋯O close contacts occur. The crystal packing is stabilized by inter-molecular C-H⋯O hydrogen bonds.

1-[4-(ß-d-Allopyranos-yloxy)benzyl-idene]semicarbazide hemihydrate.

The mol-ecule of the title compound, C(14)H(19)N(3)O(7)·0.5H(2)O, exhibits an E conformation about the C=N double bond. The water mol-ecule possesses crystallographically imposed twofold symmetry. In the crystal structure, the mol-ecules are connected by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds into a three-dimensional network.

4-[1-Acetyl-3-(4-methoxy-phen-yl)-2-pyrazolin-5-yl]phenol.

In the title compound, C(18)H(18)N(2)O(3), the dihedral angle formed by the benzene rings is 71.75 (4)°. In the crystal structure, centrosymmetrically related mol-ecules are linked into dimers by inter-molecular O-H⋯O hydrogen bonds and π-π stacking inter-actions with centroid-centroid distances of 3.5511 (6) Å.

N-[4-(ß-d-Allopyranos-yloxy)benzyl-idene]methyl-amine.

The title compound, C(14)H(19)NO(6), was synthesized by the condensation reaction between hecilid (4-formyl-phenl-ß-d-allopyran-oside) and methyl-amine in methanol. In the crystal structure, the pyran ring adopts a chair conformation and adjacent mol-ecules are linked by inter-molecular O-H⋯O and O-H⋯N hydrogen bonds, forming a three-dimensional network.

N,N-Dimethyl-4-[(E)-phenyl-imino-meth-yl]aniline.

The title compound, C(15)H(16)N(2), contains two aromatic rings linked through an imino group. The mol-ecule exhibits an E configuration with respect to the C=N bond. The dihedral angle between the aromatic rings is 61.96 (1)°.

E-[4-(ß-d-Allopyranos-yloxy)phen-yl]-1-(4-chloro-phen-yl)prop-2-enone ethanol solvate.

The title compound, C(21)H(21)ClO(7)·C(2)H(5)OH was synthesized by the condensation reaction between helicid [systematic name: 4-(ß-d-allopyranos-yloxy)benzaldehyde] and 4-chloro-aceto-phen-one in ethanol. In the mol-ecular structure, the pyran-oside ring adopts a chair conformation. In the crystal structure, the molecules are linked by inter-molecular O-H⋯O hydrogen bonds involving the OH groups from the pyran-oside unit and from the ethanol solvent mol-ecule.

1-[4-(2,3,4,6-Tetra-O-acetyl-ß-d-allo-pyranos-yloxy)benzyl-idene]thio-semi-carbazide.

The title compound, C(22)H(27)N(3)O(10)S, was synthesized by reaction of an ethanol solution of helicid (systematic name: 4-formylphenl-ß-d-allopyranoside), thio-semicarbazide and acetic acid. The mol-ecule exhibits a trans conformation with respect to the C=N double bond. The pyran ring adopts a chair conformation. In the crystal structure, the mol-ecules are linked into chains parallel to the b axis by inter-molecular N-H⋯O hydrogen bonds.

4-Formyl-phenyl 2,3,4,6-tetra-O-acetyl-ß-d-allopyran-oside.

The title compound, C(21)H(24)O(11), crystallizes exclusively as the ß-anomer. The substituent of the protected sugar at position C-3 is in the axial position, while all other groups are in equatorial positions. The pyran-oside ring adopts a stable chair conformation.

(E)-4-(ß-d-Allopyran-os-yloxy)cinnamyl 4-bromo-phenyl ketone ethanol solvate.

The title compound, C(21)H(21)BrO(7)·C(2)H(6)O, was synthesized by the Claisen-Schimidt reaction of helicid (systematic name: 4-formyl-phenyl-ß-d-allopyran-oside) with 4-bromo-aceto-phenone in ethanol. The pyran ring adopts a chair conformation. In the crystal structure, mol-ecules are linked into a three-dimensional network by inter-molecular O-H⋯O hydrogen bonds.

Ethoxy-carbonyl-methyl ursolate.

The title compound, C(34)H(54)O(5), was synthesized by the reaction of ursolic acid with ethyl chloro-acetate in the presence of DMA. All six-membered rings of the penta-cyclic triterpene skeleton adopt chair conformations. In the crystal structure, mol-ecules are linked by inter-molecular O-H⋯O hydrogen-bond inter-actions, forming zigzag chains along the c axis.

Inhibition of Acetylcholinesterase (AChE): A Potential Therapeutic Target to Treat Alzheimer's Disease.

A new series of icariin derivatives were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. Most of the tested compounds exhibited high AChE inhibition and low toxicity, and among which compounds 1, 2, and 10 were the most potent (IC50  = 71.52 ± 22.43, 8.28 ± 1.45, 5.830 ± 1.78 nm, respectively).