Liang-Peng Sun

Synthesis and antimicrobial evaluation of l-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone

Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL.

Synthesis and biological evaluation of rhodanine derivatives bearing a quinoline moiety as potent antimicrobial agents

Three series of rhodanine derivatives bearing a quinoline moiety (6a-h, 7a-g, and 8a-e) have been synthesized, characterized, and evaluated as antibacterial agents. The majority of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, 6g and 8c were identified as the most effective with minimum inhibitory concentration (MIC) values of 1 μg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus (MRSA and QRSA, respectively). None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL. The cytotoxic activity assay showed that compounds 6g, 7g and 8e exhibited in vitro antibacterial activity at non-cytotoxic concentrations. Thus, these studies suggest that rhodanine derivatives bearing a quinoline moiety are interesting scaffolds for the development of novel Gram-positive antibacterial agents.

Synthesis and antibacterial evaluation of rhodanine-based 5-aryloxy pyrazoles against selected methicillin resistant and quinolone-resistant Staphylococcus aureus (MRSA and QRSA)

With an intention to synergize the anti-bacterial activity of 5-aryloxy pyrazole and rhodanine derivatives, eight series of hybrid compounds have been synthesized and evaluated for their antibacterial activity. The majority of the synthesized compounds showed good inhibitory activity against selected methicillin resistant and quinolone-resistant Staphylococcus aureus (MRSA, QRSA) with minimum inhibitory concentration (MIC) values in the range of 1-32 μg/mL. The cytotoxicity test suggests that these compounds exhibited in vitro antibacterial activity at non-cytotoxic concentrations. These studies therefore suggest that rhodanine-based 5-aryloxy pyrazoles are interesting scaffolds for the development of novel Gram-positive antibacterial agents.

Synthesis and biological evaluation of 1,3-diaryl pyrazole derivatives as potential antibacterial and anti-inflammatory agents.

Three series of 1,3-diaryl pyrazole derivatives bearing aminoguanidine or furan-2-carbohydrazide moieties have been synthesized, characterized and evaluated for antibacterial and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains with minimum inhibitory concentration values in the range of 1-64 μg/mL. Compounds 6g, 6l and 7l presented the most potent inhibitory activity against Gram-positive bacteria (e.g. Staphylococcus aureus 4220), Gram-negative bacteria (e.g. Escherichia coli 1924) and the fungus, Candida albicans 7535, with minimum inhibitory concentration values of 1 or 2 μg/mL. Compared with previous studies, these compounds exhibited a broad spectrum of inhibitory activity. Furthermore, compound 7l showed the greatest anti-inflammatory activity (93.59% inhibition, 30 min after intraperitoneal administration), which was more potent than the reference drugs ibuprofen and indomethacin.

Synthesis and Biological Evaluation of 2,4,6‐Trihydroxychalcone Derivatives as Novel Protein Tyrosine Phosphatase 1B Inhibitors

A series of 2,4,6‐trihydroxychalcone derivatives were synthesized and identified as reversible and competitive protein tyrosine phosphatase (PTP) 1B inhibitors with IC50 values in the micromolar range. Compound 4a had the greatest in vitro inhibition activity against PTP1B (IC50 = 0.27 ± 0.01 μm) and the best selectivity (6.9‐fold) for PTP1B relative to T‐cell protein tyrosine phosphatases. The compounds identified herein provide a foundation on which to design specific inhibitors of PTP1B and other PTPs.

Synthesis and biological evaluation of 5-aryloxypyrazole derivatives bearing a rhodanine-3-aromatic acid as potential antimicrobial agents

Three novel series of 5-aryloxypyrazole derivatives have been synthesized and tested for their antibacterial activity. The majority of the synthesized compounds showed potent inhibitory activity against Gram-positive bacteria Staphylococcus aureus 4220, especially against the strains of multidrug-resistant clinical isolates (MRSA3167/3506 and QRSA3505/3519). Among which compounds IIIb, IIIg and IIIm showed the most potent levels of activity (MIC=1 μg/mL) against the multidrug-resistant strains. And cytotoxic activity assay showed that the compounds tested did not affect cell viability on the Human cervical (HeLa) cells at their MICs. The current study therefore suggests that 5-aryloxypyrazoles bearing a rhodanine-3-aromatic acid moiety are promising scaffolds for the development of novel Gram-positive antibacterial agents.

Synthesis and antibacterial activity of novel 1,3-diphenyl-1H-pyrazoles functionalized with phenylalanine-derived rhodanines.

In the present study, a series of novel 1,3-diphenyl-1H-pyrazoles functionalized with phenylalanine-derived rhodanine derivatives were synthesized and evaluated for their antibacterial activity. Compounds 4, 6, 9, 10, 12 and 15 exhibited stronger activity than the standard drugs, norfloxacin and oxacillin, with MIC values of 1 μg/mL against methicillin-resistant Staphylococcus aureus and quinolone-resistant S. aureus. None of the compounds showed any activity against Gram-negative bacteria.

Synthesis and biological evaluation of chalcone derivatives containing aminoguanidine or acylhydrazone moieties

Three novel series of chalcone derivatives containing an aminoguanidine or acylhydrazone moiety were designed, synthesized and evaluated in terms of their antibacterial, antifungal and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibitory activity towards various bacteria and one fungus with minimum inhibitory concentrations (MICs) ranging from 1 to 8μg/mL. Compared with our previously reported chalcone derivatives (MICs >64μg/mL), these compounds exhibited improved antibacterial activities (MICs=2μg/mL) against Gram-negative bacterial strains (Escherichia coli 1924 and 1356). Compounds 4f and 4h were found to be the most potent with an MIC value of 1μg/mL against the Gram-negative bacterial strains Salmonella typhimurium 1926 and the fungus Candida albicans 7535. In addition, compound 4f displayed the most potent anti-inflammatory activity of all of the compounds prepared in the current study with 92.45% inhibition after intraperitoneal administration, making it more potent than the reference drugs indomethacin and ibuprofen. The cytotoxic activity of the compound 4f was assessed in HeLa, Hep3B and L02 cells.

Synthesis and Biological Evaluation of [1,2,4]Triazolo[3,4-a]phthalazine and Tetrazolo[5,1-a]phthalazine Derivatives Bearing Substituted Benzylpiperazine Moieties as Positive Inotropic Agents

Two series of [1,2,4]triazolo[3,4‐a]phthalazine and tetrazolo[5,1‐a]phthalazine derivatives bearing substituted benzylpiperazine moieties have been synthesized and evaluated for their positive inotropic activity by measuring left atrium stroke volume on isolated rabbit heart preparations. The majority of the derivatives exhibited better in vitro activity than the existing drug, milrinone, and 6‐((4‐(4‐methoxyphenyl)piperazin‐1‐yl)methyl)tetrazolo[5,1‐a]phthalazine. 8 m in particular was identified as the most potent with an increased stroke volume of 12.02 ± 0.20% (milrinone: 2.46 ± 0.07%) at a concentration of 3 × 10–5 m. The chronotropic effects of the compounds that exhibited good potency were also evaluated.

Synthesis and biological evaluation of (+/-)-3-(2-(2-fluorobenzyloxy) naphthalen-6-yl)-2-aminopropanoic acid derivatives as novel PTP1B inhibitors

A series of novel nonphosphonate-based pTyr mimetics comprised (±)-3-(2-(2-fluorobenzyloxy)naphthalen-6-yl)-2-aminopropanoic acid derivatives were identified as reversible and competitive PTP1B inhibitors via a structure-based design approach. Among the compounds studied, 12h was found to have the best in vitro inhibition activity against PTP1B (IC(50) = 1.25 ± 0.24 μM) and the best selectivity (3-fold) between PTP1B and TCPTP. These results should provide suitable druglike lead compounds for the design of inhibitors of PTP1B as well as other PTPs.