Hu-Ri Piao

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.

Novel dammarane-type sapogenins from Panax ginseng berry and their biological activities

Three new dammarane-type sapogenins (1, 3, and 5) together with two known ones (2 and 4) were isolated from the total hydrolyzed saponins extracted from Panax ginseng berry. Their structures were elucidated using a combination of 1D and 2D (1)H and (13)C NMR spectra and mass spectroscopy as 20(R)-25-methoxyl-dammarane-3β,12β,20-triol (1), 20(R)-25-methoxyl-dammarane-3β,6α,12β,20-tetrol (2), 20(R)-20-methoxyl-dammarane-3β,12β,25-triol (3), 20(R)-20,25-dimethoxyl-dammarane-3β,12β-diol (4), and (12R,20S,24S)-20,24-; 12,24-diepoxy-dammarane-3β-ol (5). Their antitumor activities were evaluated in six human cancer cell lines. The novel compounds 1 and 3 showed significant cytotoxic activity against the six cell lines. The IC(50) values of 3 against HepG2, Colon205, and HL-60 were the lowest (8.78, 8.64, and 3.98 μM, respectively). Compounds 1 and 20(S)-25-OCH(3)-PPD, which are a pair of configuration isomers, showed a 10- to 100-fold greater growth inhibition than ginsenoside-Rg(3) (an anti-cancer clinical agent in China). The data presented here may be useful for the development of novel anti-cancer agents.

Synthesis and bioactivity evaluation of rhodanine derivatives as potential anti-bacterial agents

Five series of (Z)-5-(4-(2-oxo-2-phenylethoxy)benzylidene)-2-thioxothiazolidin-4-one derivatives (I-V) were synthesized, characterized, and evaluated for their anti-bacterial activity. Most of the synthesized compounds showed potent inhibition against several Gram-positive bacteria (including multidrug-resistant clinical isolates) with MIC values in the range of 1-32 μg/mL. Compounds IIIi, Vb and Vc presented the most potent activity, showing four-fold more potency than norfloxacin (MIC = 8 μg/mL and 4 μg/mL) and 64-fold more activity than oxacillin (MIC > 64 μg/mL) against MRSA CCARM 3167 and 3506 strains with MIC values of 1 μg/mL, and 64-fold more potency than norfloxacin (MIC > 64 μg/mL) and comparable activity to oxacillin (MIC = 1 μg/mL) against the QRSA CCARM 3505 and 3519 strains. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 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 Anti‐Bacterial Activity of Some Heterocyclic Chalcone Derivatives Bearing Thiofuran, Furan, and Quinoline Moieties

36 Novel heterocyclic chalcone derivatives were synthesized and tested for their anti‐bacterial activity. Some compounds presented good anti‐microbial activities against Gram‐positive bacteria (including the multidrug‐resistant clinical isolates). This class of compounds presented high potency against Streptococcus mutans, among which the derivatives F2 with an MIC of 2 µg/mL was as active as the standard drug (norfloxacin) and less active than oxacillin. All the compounds did not inhibit the growth of Gram‐negative bacteria (Escherichia coli CCARM 1924 or Escherichia coli CCARM 1356) at 64 µg/mL.

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.

Design, synthesis of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-ones with anticonvulsant activity.

A new series of 8-alkoxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one derivatives were synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The results showed that 8-heptyloxy-5,6-dihydro-[1,2,4]triazino[4,3-a]quinolin-1-one 5t was the most potent with median effective dose (ED(50)) value of 11.4 mg/kg, median toxicity dose (TD(50)) of 114.1 mg/kg, providing a protective index (PI=TD(50)/ED(50)) value of 10.0, which is much greater than the PI of the prototype drug carbamazepine (PI=6.4). To explain the possible mechanism of anticonvulsant activity, the compound 5t was tested in chemically induced seizures.

Synthesis and anticonvulsant activity of N-(2-hydroxyethyl) cinnamamide derivatives.

A series of novel N-(2-hydroxyethyl) cinnamamide derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The MES test showed that compounds I(N-(2-hydroxyethyl) cinnamamide) and 1d ((E)-3-(3-fluorophenyl)-N-(2-hydroxyethyl)acrylamide) were found to possess better anticonvulsant activity but also had lower toxicity. In the anti-MES potency test, these compounds exhibited median effective dose (ED(50)) of 17.7 and 17.0 mg/kg, respectively, and median toxicity dose (TD(50)) of 154.9 and 211.1, respectively, resulting in a protective index (PI) of 8.8 and 12.4, respectively, which is much greater than the PI of the marked antiepileptic drug carbamazepine. To further investigate the effects of the anticonvulsant activity in several different models, compounds I and 1d were tested against convulsions induced by chemical substances, including pentylenetetrazole (PTZ), isoniazid, 3-mercaptopropionic acid, and thiosemicarbazide.

Synthesis and positive inotropic activity of N-(4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(piperazin-1 -yl)acetamide derivatives

A series of N-(4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(piperazin-1-yl)acetamide derivatives were synthesized and their positive inotropic activity was evaluated by measuring left atrium stroke volume on isolated rabbit heart preparations. Several compounds showed favorable activity compared with the standard drug, milrinone, among which N-(1-benzyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-7-yl)-2-(4-benzylpiperazin-1-yl)acetamide 6j was found to be the most potent with the 13.2% increased stroke volume (milrinone 4.7%) at concentration of 3x10(-5) M in our in vitro study. The chronotropic effects of those compounds having inotropic effects were also evaluated in this work.

Synthesis and antimicrobial evaluation of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety

Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 μg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 μg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 μg/ml. All of the compounds synthesized in the current Letter were characterized by (1)H NMR, (13)C NMR, infrared and mass spectroscopy.