A series of 1-methyl-1H-indole–pyrazoline hybrids were designed, synthesized, and biologically evaluated as potential tubulin polymerization inhibitors. Among them, compound e19 [5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide] showed the most potent inhibitory effect on tubulin assembly (IC₅₀=2.12 μm) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC₅₀ values of 0.21–0.31 μm). Further studies confirmed that compound e19 can induce HeLa cell apoptosis, cause cell-cycle arrest in G₂/M phase, and disrupt the cellular microtubule network. These studies, along with molecular docking and 3D-QSAR modeling, provide an important basis for further optimization of compound e19 as a potential anticancer agent.

A novel series of 1,3-diphenyl-2-propen-1-one (chalcone) derivatives was synthesized by a simple, eco-friendly, and efficient Claisen–Schmidt condensation reaction and used as precursors for the synthesis of new pyrazoline derivatives. All the synthesized compounds were screened for anti-inflammatory related activities such as inhibition of phospholipase A₂ (PLA₂), cyclooxygenases (COX-1 and COX-2), IL-6, and TNF-α. The results of the above studies show that the compounds synthesized are effective inhibitors of above pro-inflammatory enzymes and cytokines. Overall, the results of the studies reveal that the pyrazolines with chlorophenyl substitution (1b–6b) seem to be important for inhibition of enzymes and cytokines. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX-inhibitory activities of the investigated compounds.

Interference with dynamic equilibrium of microtubule–tubulin has proven to be a useful tactics in the clinic. Based on investigation into the structure–activity relationship (SAR) studies of tubulin polymerization inhibitors obtained from several worldwide groups, we attempted to design 691 compounds covering several main heterocyclic scaffolds as novel colchicine-site inhibitors (CSIs). Evaluated by a series of combination of commonly used computer methods such as molecular docking, 3D-QSAR, and pharmacophore model, we can obtain the ultimate 16 target compounds derived from five important basic scaffolds in the field of medicinal chemistry. Among these compounds, compound A-132 with in silico moderate activity was synthesized, and subsequently validated for preliminary inhibition of tubulin polymerization by immunofluorescence assay. In additional, the work of synthesis and validation of biological activity for other 15 various structure compounds will be completed in our laboratory. This study not only developed a hierarchical strategy to screen novel tubulin inhibitors effectively, but also widened the spectrum of chemical structures of canonical CSIs.

VEGFR2 has been proved to play a major role in the regulation of tumor angiogenesis. Twenty-one 4-alkoxyquinazoline-based derivatives have been designed and synthesized as vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors, and their biological activities were evaluated. Among these compounds, compound 3h exhibited the most potent inhibitory activities against VEGFR2 tyrosine kinase and cell proliferation, with the IC₅₀ values of 2.89 nm (for VEGFR2) and 0.25 μm (for MCF-7), which were comparable with the control compound. Docking simulation was performed to position compound 3h into the 4ASE active site, and the result showed that compound 3h could bind well at the 4ASE active site.

In this study, we synthesized a series of dihydropyrazole sulfonamide derivatives containing 2-hydroxyphenyl moiety as antitumor agents to target the matrix metalloproteinase-2 (MMP-2). All of the synthesized compounds were examined by bioactivity assays, in which compound 4c turned out as a potential antagonist of MMP-2 along with potent anticancer activity against four tumor cell lines. Structure–activity relationship analysis was also performed to examine how structural changes impacted the bioactivity. Suggested to be caused by the induction of apoptosis, the antitumor mechanism of 4c was further confirmed by PI combining with annexin V-FITC staining assay using flow cytometry analysis. These new findings along with molecular docking observations suggested that compound 4c could be developed as a potential anticancer agent.

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. In this manuscript, a series of novel Schiff base compounds were designed and synthesized, and their biological activities were evaluated as potential inhibitors. Among these 21 new compounds, (E)-N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)methylene)hexadecan-1-amine (10) showed the most potent antibacterial activity with a MIC value of 3.89–7.81 μM⁻¹ against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with an IC₅₀ value of 1.6 μM. Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation.

Forty-three oxime derivatives were synthesized by allowing O-benzylhydroxylamines to react with primary benzaldehydes or salicylaldehydes; these products were gauged as potential inhibitors of β-ketoacyl-(acyl-carrier-protein) synthase III (FabH). Among the 43 compounds, 38 are reported herein for the first time. These compounds were assayed for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Pseudomonas fluorescens, Bacillus subtilis, Staphylococcus aureus, and Enterococcus faecalis. Compounds with prominent antibacterial activities were tested for their E. coli FabH inhibitory activities. 3-((2,4-Dichlorobenzyloxyimino)methyl)benzaldehyde O-2,4-dichlorobenzyl oxime (44) showed the best antibacterial activity, with minimum inhibitory concentrations of 3.13–6.25 μg mL⁻¹ against the tested bacterial strains, exhibiting the best E. coli FabH inhibitory activity, with an IC₅₀ value of 1.7 mM. Docking simulations were performed to position compound 44 into the E. coli FabH active site in order to determine the most probable binding conformation.

A series of 3,5-diiodo-salicylalidene Schiff bases (compounds 1–35) has been synthesized and tested for antimicrobial activity. The compounds were assayed for antibacterial activities by the MTT method. Some of the compounds inhibit the growth of a broad range of bacteria including the species of Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Enterobacter cloacae. Among them, compounds 2-[(4-chloro-phenylimino)methyl]-4,6-diiodo-phenol 11 and 2,4-diiodo-6-[(2-morpholin-4-yl-ethylimino)methyl]phenol 19 showed the most potent antibacterial activity with MIC of 3.1, 12.9, 3.3, 6.5, 12.9, 3.3 and 3.2, 12.8, 3.2, 12.8, 12.8, 3.2 μM against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. Coli, and E. cloacae, respectively.

In the search for potential immunosuppressive agents with high efficacy and low toxicity, a series of new deoxybenzoins were synthesized and evaluated for their cytotoxicity and immunosuppressive activity. Among the synthesized compounds, four deoxybenzoin oximes (compounds 31, 32, 37, and 38) exhibited lower cytotoxicity and higher inhibitory activity toward anti-CD3/anti-CD28 co-stimulated T-cell proliferation than other compounds. More significantly, compound 31 is >100-fold less cytotoxic than cyclosporine A (CsA) and is also more potent (31: SI>684.64, CsA: SI=235.44). The preliminary inhibition mechanism of compound 31 was also identified by flow cytometry, and this compound exerts immunosuppressive activity by inducing apoptosis in activated lymph node cells in a dose-dependent manner. In addition, the mechanism of apoptosis was detected by western blot analysis.

A series of new metronidazole–deoxybenzoin derivatives were synthesized and evaluated for their antimicrobial activity against Helicobacter pylori. Highly selective anti-H. pylori activity was also observed in synthesized compounds. Compound 34 exhibited the most potent activity, similar to the positive control amoxicillin. Furthermore, compounds 17 and 34 were able to significantly decrease H. pylori water extract (HPE)-induced production of interleukin-8 (IL-8) in gastric mucosal cells, which did not show any effect on the cell viability.

Eleven novel 5-methyl-2-[(un)substituted phenyl]-4-{4,5-dihydro-3-[(un)substituted phenyl]-5-(1,2,3,4-tetrahydroisoquinoline-2-yl)pyrazol-1-yl}-oxazole derivatives were synthesized and characterized by elemental analysis, ESI-MS, ¹H NMR and ¹³C NMR. All of the compounds have been screened for their antiproliferative activities against PC-3 cell (human prostate cancer) and A431 cell (human epidermoid carcinoma cancer) lines in vitro. The results revealed that compounds 4g, 4j and 4k exhibited the strong inhibitory activities against the PC-3 cell lines (with IC₅₀ values of 2.8±0.11, 3.1±0.10 and 3.0±0.06 μg/mL, respectively).

Thirteen resveratrol (=5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol) analogues with a CHO group have been prepared by partial synthesis from resveratrol. The synthesized compounds have been evaluated for their cytotoxic activity against a human nasopharyngeal epidermoid tumor cell line KB, as well as for their xanthine oxidase inhibitory activity. Compounds 2, 3, and 6a showed the most significant cytotoxic activities against the cell line KB, and compound 2 also exhibited strong xanthine oxidase inhibitory activity.

The antiproliferative activities of 36 3-aryl-1H-quinolin-4-ones were determined against two cancer cell lines (Hep G2 and KB) in vitro. The results indicate that most of these compounds show good cytotoxic activity against human cancer cell lines, but no cytotoxicity against a human normal cell line (L02). The positive control compounds genistein and 5-fluorouracil show no selectivity at inhibiting the growth of the above three cell lines. Generally, compounds that bear a halogen atom at the 8 position and a methoxy group at the 3′ position exhibited remarkable cytotoxicity toward human cancer cell lines. Electron-withdrawing substituents at the 6 position decrease the antiproliferative activity significantly. We also put forward a pharmacophore model for 3-aryl-4-quinolinones binding with epidermal growth factor receptor protein tyrosine kinases (EGFR PTK). Out of the 36 synthetic compounds, 34 are reported for the first time.