HSCVFNT: Inference of Time-Delayed Gene Regulatory Network Based on Complex-Valued Flexible Neural Tree Model.

Gene regulatory network (GRN) inference can understand the growth and development of animals and plants, and reveal the mystery of biology. Many computational approaches have been proposed to infer GRN. However, these inference approaches have hardly met the need of modeling, and the reducing redundancy methods based on individual information theory method have bad universality and stability.

Discovery of benzenesulfonamide derivatives as potent PI3K/mTOR dual inhibitors with in vivo efficacies against hepatocellular carcinoma.

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is related to cellular activities. Abnormalities of this signaling pathway were discovered in various cancers, including hepatocellular carcinoma (HCC). The PI3K/mTOR dual inhibitors were proposed to have enhanced antitumor efficacies by targeting multiple points of the signaling pathway.

Design, Synthesis and Biological Evaluation of 1,4-Disubstituted-3,4-dihydroisoquinoline Compounds as New Tubulin Polymerization Inhibitors.

A series of 1,4-disubstituted-3,4-dihydroisoquinoline derivatives designed as tubulin polymerization inhibitors were synthesized. Their cytotoxic activities against the CEM leukemia cell line were evaluated. Most of them displayed moderate cytotoxic activities, and compounds 21 and 32 showed good activities with IC50 of 4.

Design and synthesis of phenylisoxazole derivatives as novel human acrosin inhibitors.

Human acrosin is an attractive target for the discovery of novel male contraceptives. Isoxazole derivative ISO-1, a small-molecule weak human acrosin inhibitor, was used as the starting point for lead optimization. After two rounds of structure-based inhibitor design, a highly potent inhibitor B6 (IC50=1.

Synthesis and acrosin inhibitory activities of 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives.

A series of novel 5-phenyl-1H-pyrazole-3-carboxylic acid amide derivatives were designed, synthesized, and their acrosin inhibitory activities in vitro were evaluated. The results of the acrosin inhibitory activity showed that all target compounds were more potent than control TLCK. Compounds AQ-A1, AQ-D3, AQ-D4, AQ-E4 and AQ-E5 exhibited stronger acrosin inhibitory activities than control ISO-1.

Fragment-based design of novel quinazolinon derivatives as human acrosin inhibitors.

Human acrosin is a promising target for the male contraceptives. On the basis of the active site of human acrosin, a series of novel quinazolinon compounds were designed by a fragment docking and growing strategy. In vitro anti-acrosin assay revealed that all the compounds showed potent human acrosin inhibitory activities.

Design and synthesis of novel benzoheterocyclic derivatives as human acrosin inhibitors by scaffold hopping.

Human acrosin is an attracting target for the development of novel male contraceptives. Scaffold hopping was used to optimize the isoxazolecarbaldehyde human acrosin inhibitors and extend their structure-activity relationships. Four kinds of scaffolds, namely benzimidazole, benzothiazole, 3H-indazole, and 5-phenyl-1H-pyrazole, were designed and synthesized.

Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen-2-one as a new class of microtubule-targeting agents.

A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC(50) = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC(50) = 3.

Ethyl 5-(4-amino-phen-yl)isoxazole-3-carboxyl-ate.

The asymmetric unit of the title compound, C(12)H(12)N(2)O(3), contains two mol-ecules in which the benzene and isoxazole rings are almost coplanar, the dihedral angles between their mean planes being 1.76 (9) and 5.85 (8)°.

Synthesis and acrosin inhibitory activity of methyl 5-substituted-1H-benzo[d]imidazol-2-yl carbamate derivatives.

A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their acrosin inhibitory activities evaluated in vitro. The results of acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent acrosin inhibitory activity among all the compounds, with an IC(50) of 6.

Synthesis and biological evaluation of 1-phenyl-1,2,3,4-dihydroisoquinoline compounds as tubulin polymerization inhibitors.

A series of 1-phenyl-3,4-dihydroisoquinoline derivatives and several 1-phenyl-1,2,3,4-tetrahydroisoquinoline, 1-phenyl-isoquinoline analogues were synthesized, and their cytotoxicity and tubulin polymerization inhibitory activity were evaluated. The 1-phenyl-3,4-dihydroisoquinoline compounds were found to be potential tubulin polymerization inhibitors. Compound 5n, bearing a 3'-OH and 4'-OCH(3) substituted 1-phenyl B-ring, was shown to confer optimal bioactivity.

N-(2-Hy-droxy-eth-yl)-5-(4-meth-oxy-phen-yl)-4H-pyrazole-3-carboxamide.

In the title compound, C(13)H(15)N(3)O(3), the dihedral angle between the benzene and pyrazole rings is 7.7 (1)° and the O-C-C-N torsion angle of the side chain is 74.1 (2)°.

Design, synthesis, and activity evaluation of broad-spectrum small-molecule inhibitors of anti-apoptotic Bcl-2 family proteins: characteristics of broad-spectrum protein binding and its effects on anti-tumor activity.

On the basis of the comparison of the structure of the Bim BH3: Bcl-x(L) complex and that of the ABT-737: Bcl-x(L) complex, a series of class A compounds were designed. These compounds had the basic skeleton of ABT-737 and the h2 residues of Bim BH3. These residues had shown themselves to be relevant to Bim BH3's broad-spectrum binding properties in saturation mutagenesis assays.

Synthesis and acrosin inhibitory activity of substituted 4-amino-N-(diaminomethylene) benzenesulfonamide derivatives.

A series of new substituted 4-amino-N-(diaminomethylene) benzenesulfonamides were synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds showed potent acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N-alpha-tosyl-L-lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of acrosin inhibitory agents.

Synthesis and acrosin inhibitory activities of substituted ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives.

A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives were designed and synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds exhibited acrosin inhibitory activities. Among them, three compounds (5l, 5n, and 5v) were more potent than that of the control TLCK.

Imidazolone-amide bridges and their effects on tubulin polymerization in cis-locked vinylogous combretastatin-A4 analogues: synthesis and biological evaluation.

A series of novel combretastatin-A4 analogues in which the cis-olefinic bridge is replaced by an imidazolone-amide were synthesized, and their cytotoxicity and tubulin-polymerization inhibitory activities were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 10, 9b and 9c, bearing 3'-NH₂-4'-OCH₃, 4'-CH₃ and 3'-CH₃-substituted 1-phenyl B-ring, confer optimal bioactivity.

Design and synthesis of novel pyrazino[2,1-a]isoquinolin derivatives with potent antifungal activity.

A series of novel pyrazino[2,1-a]isoquinolin compounds were designed, synthesized, and their antifungal activities in vitro were evaluated. The results showed that all of the title compounds exhibited antifungal activities. Most of them exhibited stronger antifungal activities than the lead compounds; compound 7c is more potent than fluconazole against two of the three tested fungal strains.

Synthesis and antifungal activities in vitro of novel pyrazino [2,1-a] isoquinolin derivatives.

A series of novel pyrazino[2,1-a]isoquinolin compounds were designed and synthesized, and their antifungal activities in vitro were evaluated. The results showed that all of the compounds exhibited antifungal activities. Some of them exhibited stronger antifungal activities than that of lead compounds and among them compound 11b was the most potent one, which showed more potent than that of the active control fluconazole to the four of the five tested fungi.