Peng-Cheng Lv

Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents

Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity. Compound 3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) displayed the most potent EGFR inhibitory activity with IC₅₀ of 0.07 μM, which was comparable to the positive control erlotinib. Docking simulation was performed to position compound C5 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the pyrazole derivatives own high antiproliferative activity against MCF-7. Compound C5 showed significant antiproliferative activity against MCF-7 with IC₅₀ of 0.08 μM. Therefore, compound C5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.

Design, synthesis and biological evaluation of thiazolidinone derivatives as potential EGFR and HER-2 kinase inhibitors

Two series of thiazolidinone derivatives designing for potential EGFR and HER-2 kinase inhibitors have been discovered. Some of them exhibited significant EGFR and HER-2 inhibitory activity. Compound 2-(2-(5-bromo-2-hydroxybenzylidene)hydrazinyl)thiazol-4(5H)-one (12) displayed the most potent inhibitory activity (IC(50)=0.09 microM for EGFR and IC(50)=0.42 microM for HER-2), comparable to the positive control erlotinib. Docking simulation was performed to position compound 12 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the thiazolidinone derivatives own high antiproliferative activity against MCF-7. Compound 12 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.

Synthesis, molecular docking and biological evaluation of metronidazole derivatives as potent Helicobacter pylori urease inhibitors

Fourteen metronidazole derivatives (compounds 3a-f and 4b-h) have been synthesized by coupling of metronidazole and salicylic acid derivatives. All of them are reported for the first time. Their chemical structures are characterized by (1)H NMR, MS, and elemental analysis. The inhibitory activities against Helicobacter pylori urease have been investigated in vitro and many compounds have showed promising potential inhibitory activities of H. pylori urease. The effect of compounds 4b (IC(50)=26 microM) and 4 g (IC(50)=12 microM) was comparable with that of acetohydroxamic acid, a well known H. pylori urease inhibitor used as a positive control. The experimental values of IC(50) showed that inhibitor was potent urease inhibitor. A docking analysis using the autodock 4.0 program could explain the inhibitory activities of compound 4 g against H. pylori urease.

Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents.

Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 μM, which was comparable to the positive control. Molecular docking results indicated that compound 11 was nicely bound to the EGFR kinase. Compound 11 also showed significant antiproliferative activity against MCF-7 with IC(50) of 0.07 μM, which would be a potential anticancer agent.

Design, synthesis, and structure-activity relationships of pyrazole derivatives as potential FabH inhibitors

Fatty acid biosynthesis is essential for bacterial survival. FabH, beta-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Fifty-six 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-(4-fluorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (12) and 1-(5-(4-chlorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (13) were potent inhibitors of E. coli FabH.

Synthesis and biological evaluation of novel luteolin derivatives as antibacterial agents

A series of luteolin derivatives 2-20 were prepared, 3-20 of which were first reported. The chemical structures of these compounds were confirmed by means of 1H NMR, ESI-MS and elemental analyses. The compounds were assayed for antibacterial (Bacillus subtilis, Staphylococcus aureus, Pseudomonas fluorescens and Escherichia coli) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trtrazolium bromide) method. Among the compounds tested, most of them displayed significant activity against the tested strains, and 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-hydroxy-7-(2-(3-morpholinopropylamino)ethoxy)-4H-chromen-4-one (17) showed the most favorable antibacterial activity in vitro with MICs of 1.562, 3.125, 3.125, and 6.25 microg/mL against B. subtilis, S. aureus, P. fluorescens and E. coli, respectively. Structure-activity relationships (SAR) were also discussed based on the obtained experimental data.

Design, synthesis and biological evaluation of novel thiazole derivatives as potent FabH inhibitors

Fatty acid biosynthesis is essential for bacterial survival. Components of this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. FabH, beta-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram positive and negative bacteria. Three series of Schiff bases containing thiazole template were synthesized and developed as potent inhibitors of FabH. This inhibitor class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 11 and 18 were potent inhibitors of E. coli FabH.

Synthesis and antiproliferative activity of indolizine derivatives incorporating a cyclopropylcarbonyl group against Hep-G2 cancer cell line.

Indolizine and annulated indolizine derivatives incorporating a cyclopropylcarbonyl group were synthesized in a one pot procedure by the tanden reactions of [3+2] cycloaddition of the corresponding N-ylide with electron deficient alkene. Seventeen indolizine derivatives were reported for the first time. All the compounds were examined for their antiproliferative activity against the human hepatocellular liver carcinoma (Hep-G2) cell line by MTT method. Among the compounds tested, 5a, 5d, 5 g and 5 j showed the most favorable activities with IC(50) values of 0.39, 0.48, 0.29 and 0.20 microg/mL. Especially, compound 5 j displayed potent antiproliferative activities with IC(50) value of 0.20 microg/mL, and showed significant EGFR kinase inhibitory activity with IC(50) value of 0.085 microM. Docking simulations of 5 j were carried out to illustrate the binding mode of the molecular into the EGFR active site.

Amines and oximes derived from deoxybenzoins as Helicobacter pylori urease inhibitors

Twenty amines and oximes from deoxybenzoins were prepared and evaluated for their inhibitory activity against Helicobacter pylori urease. Among these compounds, high inhibitory activities were observed in amines and oximes, especially amines 1b (IC(50)=0.011 mM) and 6b (IC(50)=0.047 mM) exhibited good in vitro activities, and were comparable to acetohydroxamic acid (AHA). The hydroxyl groups on deoxybenzoin skeleton may be responsible for the inhibitory activity and coordinate with the nickel (active site) on enzyme. A direct interaction may exist between the OH group of hydroxylamines or NH group of amines and His alpha323 of H. pylori urease, which is on the flap of the enzyme active site.

Synthesis and antibacterial activities of metal(II) complexes with Schiff bases derived from 3,5-diiodosalicylaldehyde

Two new Schiff bases (2,4-diiodo-6-[(2-morpholin-4-yl-ethylimino)-methyl]-phenol and 2,4-diiodo-6-[(3-morpholin-4-yl-propylimino)-methyl]-phenol), condensed from 3,5-diiodosalicylaldehyde with 2-morpholinoethylamine and 3-morpholinopropylamine, have been designed and synthesized. Reaction of the Schiff bases with Zn(OAc)2 · 2H2O, Cu(OAc)2 · H2O, Ni(OAc)2 · 4H2O, Co(OAc)2 · 4H2O, Cd(OAc)2 · 2H2O, Mn(OAc)2 · 4H2O, Fe(SO4)2 · 7H2O, and Hg(OAc)2 led to the formation of 16 new mononuclear complexes. The complexes were characterized by UV, Infrared, ESI-MS, and elemental analyses, and 3,5-diiodosalicylalidene-2-morpholinoethylaminozinc(II) (1) and 3,5-diiodosalicylalidene-2-morpholinoethylaminocopper(II) (2) were characterized by single crystal X-ray diffraction. Based on crystal structural analysis of 1 and 2, coupled with their spectral similarity with 3–16, it can be concluded that 3–16 have structures similar to 1 and 2. All the complexes were assayed for antibacterial activities against three Gram positive bacterial strains (Bacillus subtilis, Staphylococcus aureus, and Streptococcus faecalis) and three Gram negative bacterial strains (Escherichia coli, Pseudomonas aeruginosa, and Enterobacter cloacae) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. Among the complexes tested, 8 and 16 showed the most favorable antibacterial activity with minimum inhibitory concentration of 0.781, 12.5, 6.25, 3.125, 3.125, 6.25 and 1.562, 6.25, 1.562, 3.125, 3.125, 1.562 µg mL−1 against B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. coli, and E. cloacae, respectively.