Synthesis and potent antimicrobial activity of some novel methyl or ethyl 1H-benzimidazole-5-carboxylates derivatives carrying amide or amidine groups

A series of benzimidazole-5-carboxylic acid alkyl ester derivatives carrying amide or amidine substituted methyl or phenyl groups at the position C-2 were synthesised and evaluated for antibacterial and antifungal activities against S. aureus, methicillin resistant S. aureus (MRSA), S. faecalis, methicillin resistant S. epidermidis (MRSE), E. coli and C. albicans. The results showed that while all simple acetamides are essentially inactive, aromatic amides and amidines have potent antibacterial activities. Aromatic amidine derivatives 13 f-h exhibited the best inhibitory activity with 1.56-0.39 microg/mL MIC values against MRSA and MRSE.     

Synthesis and anticonvulsant activity of novel and potent 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-ones

The synthesis and anticonvulsant activity of 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-(thi)ones (4a-d) and their 3-N-alkylcarbamoyl derivatives (4e-h) are reported. The new compounds possess marked anticonvulsant properties, comparable to those of the dehydro analogues 3 and higher than that of GYKI 52466 (1). Noteworthy, compound 4c shows a longer-lasting anticonvulsant activity. Electrophysiological experiments show that derivative 4c is less effective than 1 and 3c to reduce the KA-evoked currents in cerebellar granule neurons.     

Synthesis and antimicrobial activity of some isoindolin-1-ones derivatives

A range of N-substituted isoindolin-1-ones was prepared and their potential as novel antimicrobial agents was investigated. MIC values for active compounds were determined and reported.     

Synthesis and antimicrobial activity of 2-alkenylchroman-4-ones, 2-alkenylthiochroman-4-ones and 2-alkenylquinol-4-ones

2-Alkenylchroman-4-ones, 2-alkenylthiochroman-4-ones, and 2-alkenylquinol-4-ones were prepared with very good regioselectivity by Me3SiOTf-mediated conjugate addition of alkenylmagnesium bromides and alkenyllithium compounds to chromones thiochromones, and quinol-4-ones. A number of products exhibit a considerable antimicrobial activity. The best activity, with respect to the spectrum of antimicrobial activity, was observed for 2-vinylchroman-4-ones containing an unsubstituted vinyl group and a chloride group located at the chromanone moiety.     

Synthesis,selective anti-Helicobacter pylori activity,and cytotoxicity of novel N-substituted-2-oxo-2H-1-benzopyran-3-carboxamides

N-substituted-3-carboxamido-coumarin derivatives were prepared and evaluated for selective antibacterial activity against 20 isolates of Helicobacter pylori clinical strains, including five metronidazole resistant ones. Some of them possessed the best activity against H. pylori metronidazole resistant strains with MIC values lower than the drug reference (metronidazole). Furthermore, anti-inflammatory activity through the inhibition of the IL-8 production was investigated.     

Synthesis, analgesic, anti-inflammatory, and antimicrobial activity of some novel pyrimido[4,5-b]quinolin-4-ones

Novel series of pyrimido[4,5-b]quinolines (3a-c), triazolo[4',3':1,2]pyrimido[4,5-b]-quinolines (7a-e, 9, and 14), tetrazolo[4',3':1,2]pyrimido[4,5-b]quinolin-5-one (13), [1,3]-pyrazolo[3',2':1,2]pyrimido[4,5-b]quinolines (12a and 12b), and 2-pyrazolyl-pyrimido[4,5-b]-quinolines (15, 16a, 16b, and 19) have been synthesized. Some of the new compounds were tested against various bacteria and fungi species. In addition, the analgesic and anti-inflammatory activities are reported. Compounds 8 and 9a possess high activity toward the fungi as compared with the reference drug Nystatin. The tested compounds 5 and 8 have moderate anti-inflammatory activities. Moreover compounds 5, 8, 10, and 16a, have activities higher than the reference drug in peripheral analgesic activity testing, Compounds 5, 7a, 11a, and 16a have potencies as the reference drug in central analgesic activity testing.     

Synthesis and pharmacological evaluation of some N-arylsulfonyl-N-methyl-N'-(2,2-dimethyl-2H-1-benzopyran-4-yl)ureas structurally related to cromakalim

Some N-arylsulfonyl-N-methyl-N'-(2,2-dimethyl-2H-1-benzopyran-4-yl)ureas were prepared and evaluated as putative potassium channel openers on the vascular and uterine smooth muscle tissue (myorelaxant effect), as well as on insulin-secreting pancreatic islets (inhibition of insulin release). The pharmacological results indicated that these compounds exhibited a marked biological activity on these three tissues.     

Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors

A series of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors was discovered. Several compounds such as 15 and 20 showed good hNET potency. Compounds 15 and 20 also displayed excellent selectivity at hNET that appeared superior to those of reboxetine and atomoxetine (4 and 5).     

Synthesis and biological evaluation of some novel triazol-3-ones as antimicrobial agents

A new series of triazol-3-one derivatives bearing 4-methyl-4H-thieno[3',2': 5,6]thiopyrano[4,3-d][1,3]thiazolyl or 4-(thiophene-3-yl) thiazolyl moiety at 4-position and alkyl substitution at 2-position are synthesized. All the synthesized compounds are characterized by elemental analysis, IR, (1)H NMR, (13)C NMR, and mass spectral data. The newly synthesized compounds are screened for antifungal and antibacterial activities.     

Synthesis and estrogen receptor binding affinities of 7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-ones containing a basic side chain

Two isoflavones containing a sulfur or oxygen hinge with an amine-bearing side chain have been designed and synthesized as potential selective estrogen receptor modulators. The target compounds exhibited low affinities for estrogen receptors (ERs), and binding affinity data indicate that oxygen hinge is more favorable than sulfur for binding. These compounds also displayed selectivity for ERalpha over ERbeta.     

Synthesis and antimicrobial activity of 4-hydroxy-4-(pyridyl)alk-3-en-2-ones

4-Hydroxy-4-(pyridyl)alk-3-en-2-ones were prepared by base-mediated condensation of ketones with pyridinecarboxylates. Several derivatives show weak antimicrobial activity against Gram-positive and Gram-negative bacteria.     

Synthesis and antimicrobial activity of novel 2-thiazolylimino-5-arylidene-4-thiazolidinones

New 2-thiazolylimino-5-arylidene-4-thiazolidinones (compounds 4a-j), unsubstituted or carrying hydroxy, methoxy, nitro and chloro groups on the benzene ring, were synthesized and assayed in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria, yeasts and mould. The compounds were very potent towards all tested Gram positive microorganisms (MIC ranging from 0.03 to 6 microg/mL in most of the cases) and Gram negative Haemophilus influenzae (MIC 0.15-1.5 microg/mL), whereas no effectiveness was exhibited against Gram negative Escherichia coli and fungi up to the concentration of 100 microg/mL. The 5-arylidene derivatives showed an antibacterial efficacy considerably greater than that of the parent 2-(thiazol-2-ylimino)thiazolidin-4-one 3, suggesting that the substituted and unsubstituted 5-arylidene moiety plays an important role in enhancing the antimicrobial properties of this class of compounds. The remarkable inhibition of the growth of penicillin-resistant staphylococci makes these substances promising agents also for the treatment of infections caused by microorganisms resistant to currently available drugs.     

Volubolin,a 4-phenyl-2H-1-benzopyran-2-one from Dalbergia volubilis

From the ether soluble portion of a methanolic extract of young non-green branches of Dalbergia volubilis, sitosterol, 7-hydroxy-4-methyl-2H-1-benz     

Synthesis and antibacterial activity of some new 1-heteroaryl-5-amino-3H/methyl-4-phenylpyrazoles

The regioselective synthesis of 1-heteroaryl-5-amino-4-phenylpyrazoles 3a-g and 1-heteroaryl-5-amino-3-methyl-4-phenylpyrazoles 3h-n was achieved by the treatment of heteroarylhydrazines 1a-g with alpha-phenylformylacetonitrile 2a and alpha-phenylacetylacetonitrile 2b, respectively. The structures of the compounds 3 were established by the combined use of 1H and 13C NMR spectroscopy. All the fourteen compounds were tested for their in vitro antibacterial activity against three Gram-positive and two Gram-negative bacteria. Six compounds 3a, 3d, 3e, 3g, 3l, and 3n from this series were found to be equipotent or more potent than the commercial antibiotics (Linezolid and Cefroxime axetil).     

Synthesis and antimicrobial activity of some new N-glycosides of 2-thioxo-4-thiazolidinone derivatives

5-Arylidene-2-thioxo-4-thiazolidinones 3a-f react with each of 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl and α-d-galactopyranosyl bromides 4a,b in acetone in the presence of aqueous potassium hydroxide at room temperature to afford N-(2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl) or N-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl) 2-thioxo-4-thiazolidinone derivatives 5a-f. Similarly, the reaction of 5-cycloalkylidene-2-thioxo-4-thiazolidinones 7a,b with 4a gave the corresponding N-glucosides 8a,b. Also, 5-pyrazolidene rhodanines 10a-e react with 4a to afford the new N-glucosides 11a-e. Treatment of compounds 15 and 16 with 4a in the presence of few drops of triethylamine or in KOH solution accomplished the mono- and bis-nucleosides 17 and 18, respectively. Some selected products were tested for their antimicrobial activities.     

Synthesis and antimicrobial activity of novel 5-aminoimidazole-4-carboxamidrazones

A mild and simple method was developed to prepare a series of fifteen 5-aminoimidazole 4-carboxamidrazones, starting from the easily accessible 5-amino-4-cyanoformimidoyl imidazoles. The antimicrobial activity of these novel amidrazones was screened against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and Candida sp. (Candida albicans, Candida krusei, Candida parapsilosis). Only a subset of compounds displayed fair-moderate activity against S. aureus and E. coli but all exhibited activity against Candida sp. The three most potent antifungal compounds were further tested against Cryptococcus neoformans, Aspergillus fumigatus and three dermatophytes (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum gypseum). These three hit compounds strongly inhibited C. krusei and C. neoformans growth, although their activity on filamentous fungi was very weak when compared to the activity on yeasts.     

Synthesis and highly potent anti-inflammatory activity of licofelone- and ketorolac-based 1-arylpyrrolizin-3-ones

Since NSAIDs are commonly used anti-inflammatory agents that produce adverse effects, there have been ongoing efforts to develop more effective and less toxic compounds. Based on the structure of the anti-inflammatory pyrrolizines licofelone and ketorolac, a series of 1-arylpyrrolizin-3-ones was synthesized. Also prepared was a series of substituted pyrroles, mimicking similar known anti-inflammatory agents. The anti-inflammatory activity of the test compounds was determined with a phorbol ester (TPA)-induced murine ear edema protocol. For the most active derivatives, 19b–c/20b–c, the anti-inflammatory effect was the same as that of the reference compound (indomethacin) and was dose-dependent. These compounds have an aryl ring at the C-1 position and a methoxycarbonyl group at the C-2 position of the pyrrolizine framework, which represent plausible pharmacophore groups with anti-inflammatory activity. The anti-inflammatory activity of 1-substituted analogs containing a five- or six-membered heterocycles was lower but still good, while that of the pyrroles was only moderate. Although the docking studies suggests that the effect of analogs 19a–c/20a–c is associated with the inhibition of cyclooxygenase-2, experimental assays did not corroborate this idea. Indeed, a significant inhibition of NO was found experimentally as a plausible mechanism of action.     

A novel synthesis and antimicrobial activity of 1-[(Substituted-phenyl) sulfonyl]pyrrolidin-2-ones

Novel cyclization of 4-(substituted-phenylsulfonamido)butanoic acids to their corresponding 1-[(substituted-phenyl)sulfonyl]pyrrolidin-2-ones was successfully achieved by using polyphosphate ester (PPE). The reaction time was considerably reduced with corresponding increase in the yields, when polyphosphate ester (PPE) was used in combination with 4-(N,N-dimethylamino)pyridine (DMAP). All the synthesized compounds were screened for their antimicrobial activity. Minimum Inhibitory Concentration (MIC) values of synthesized compounds were also determined, and were found to be in the range of 0.09-1.0 mg.     

Synthesis and structure-activity relationships of 2-vinylchroman-4-ones as potent antibiotic agents

A series of novel 2-vinylchroman-4-ones, analogues of the natural products Aposphaerin A and B, were identified as potent antibiotics. Derivatives exhibit a significant activity against multiresistant strains of S. aureus, such as MRSA (methicillin resistant S. aureus). The 2-vinylchroman-4-ones were efficiently prepared by Lewis acid mediated conjugate addition of vinylmagnesium bromide to chromones.     

A novel synthesis and antimicrobial activity of 1-[(Substituted-phenyl) sulfonyl]pyrrolidin-2-ones

Novel cyclization of 4-(substituted-phenylsulfonamido)butanoic acids to their corresponding 1-[(substituted-phenyl)sulfonyl]pyrrolidin-2-ones was successfully achieved by using polyphosphate ester (PPE). The reaction time was considerably reduced with corresponding increase in the yields, when polyphosphate ester (PPE) was used in combination with 4-(N,N-dimethylamino)pyridine (DMAP). All the synthesized compounds were screened for their antimicrobial activity. Minimum Inhibitory Concentration (MIC) values of synthesized compounds were also determined, and were found to be in the range of 0.09–1.0 mg.