Design and synthesis of thiazole derivatives as potent FabH inhibitors with antibacterial activity.

Components of fatty acid biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Compounds of series A (4a-4 g) and series B (5a-5 g) were synthesized by the formation of an amine bond between aromatic acid and 4-phenylthiazol-2-amine or 4-(4-bromophenyl)thiazol-2-amine. These thiazole derivatives have evaluated as potent FabH inhibitors.

Discovery of 4,6-substituted-(diaphenylamino)quinazolines as potent c-Src inhibitors.

A series of 4,6-substituted-(diaphenylamino)quinazolines as c-Src inhibitors have been prepared and their biological activity has also been evaluated. All the compounds displayed potential antiproliferation activities, with IC50 values ranging from 3.42 μM to 118.

Design, synthesis, biological evaluation, and molecular modeling study of 4-alkoxyquinazoline derivatives as potential VEGFR2 kinase inhibitors.

A series of novel 4-alkoxyquinazoline derivatives were prepared and synthesized and their biological activities were evaluated as potential inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2). Of these compounds, compound 3j demonstrated the most potent inhibitory activities against VEGFR2 tyrosine kinase and cell proliferation, the IC50 values of this compound reaching up to 2.72 nM and 0.

Optimization of substituted 6-salicyl-4-anilinoquinazoline derivatives as dual EGFR/HER2 tyrosine kinase inhibitors.

4-Anilinoquinazolines as an important class of protein kinase inhibitor are widely investigated for epidermal growth factor receptor (EGFR) tyrosine kinase or epidermal growth factor receptor 2 (HER2) inhibition. A series of novel 6-salicyl-4-anilinoquinazoline derivatives 9-27 were prepared and evaluated for their EGFR/HER2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on three variant cancer cell lines (A431, MCF-7, and A549). The bioassay results showed most of the designed compounds exhibited moderate to potent in vitro inhibitory activity in the enzymatic and cellular assays, of which compound 21 revealed the most potent dual EGFR/HER2 inhibitory activity, with IC50 values of 0.

A functional scaffold in marine alkaloid: an anticancer moiety for human.

Marine organisms have been developed as a new source of naturally occurring alkaloids. The bioactive scaffolds of marine alkaloids govern the cross-kingdom actions, possessing "unexpectedly" cytotoxic-related antitumor activities against human cancer cell lines. And the actions of marine alkaloids toward mammalian cells have been well substantiated by the recognition of their analogues as antitumor and enzyme modulatory agents.

Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents.

A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.

Novel Schiff-base-derived FabH inhibitors with dioxygenated rings as antibiotic agents.

Fatty acid biosynthesis plays a vital role in bacterial survival and several key enzymes involved in this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Of these promising targets, β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) is the most attractive target that could trigger the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Designing small molecules with FabH inhibitory activity displays great significance for developing antibiotic agents, which should be highly selective, nontoxic and broad-spectrum.

Discovery of 6-substituted 4-anilinoquinazolines with dioxygenated rings as novel EGFR tyrosine kinase inhibitors.

It had been reported that some dioxygenated rings fusing with the quinazoline scaffold could lead to new EGFR inhibitors. Based on this, several kinds of oxygenated alkane quinazoline derivatives were synthetized and evaluated as EGFR inhibitors. Their antiproliferative activities were tested against four cancer cell lines: A431, MCF-7, A549, and B16-F10.

Hypomethylated CpG around the transcription start site enables TERT expression and HPV16 E6 regulates TERT methylation in cervical cancer cells.

Objective: The human papillomavirus (HPV) oncoprotein, E6, activates telomerase reverse transcriptase (TERT) expression and causes cellular immortalization. It remains unclear whether E6 affects TERT transcription by altering DNA methylation profiles. In this study, we explored the methylation status of the TERT promoter in cervical cancer cell lines and its variations after E6 was silenced by RNAi.

[Clinical application of telomerase RNA component gene amplification assay in cervical lesions.].

Objective: To investigate the significance of genomic amplification of the telomerase RNA component (TERC) gene to serve as a genetic biomarker in the screening of cervical lesions.

Methods: A total of 715 cases were recruited, with liquid-based cytology diagnosis as normal (n = 347), atypical squamous cells of undetermined significance (ASCUS, n = 180), atypical squamous cells cannot exclude a high-grade lesion (ASC-H, n = 13), low-grade squamous intraepithelial lesions (LSIL, n = 115), high-grade squamous intraepithelial lesions (HSIL, n = 59) and atypical glandular cells (AGC, n = 1). The remaining cervical cells in the cytological preserving fluid were analyzed using a two-color fluorescence in situ hybridization (FISH) probe targeted to chromosome 3q26 containing TERC gene.

[Evaluation of genomic amplification of the human telomerase RNA component gene in the screening of cervical lesions].

Objective: To investigate the genomic amplification of the human telomerase RNA component (hTERC) gene in cervical cytology and evaluate its role in screening of cervical lesions.

Methods: A total of 301 cases were recruited, with liquid-based cytology diagnoses as normal (n = 203), atypical squamous cells (ASC, n = 66), low-grade squamous intraepithelial lesions (LSIL, n = 18), and high-grade squamous intraepithelial lesions (HSIL, n = 14). Following cytological examination, the slides were analyzed using a two-color fluorescence in situ hybridization (FISH) probe targeted to chromosome 3q26 containing hTERC.