Anti-secretory and anti-ulcer activities of some new 2-(2-pyridylmethyl-sulfinyl)-benzimidazoles

Cereda, E.; Turconi, Marco; Ezhaya, Antoine; Bellora, E.; Brambilla, Alessandro; Pagani, F.; Donetti, A.

doi:10.1016/0223-5234(87)90293-5

Cited by 40 publications

(17 citation statements)

References 14 publications

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“…The 4-chloromethylpyrrolo[1,2-a]quinoxalines 5a to 5d (10) were then condensed with various substituted 2-mercapto derivatives in ethanol in the presence of sodium hydroxide to give the corresponding sulfides 6a to 6k (6,15). The sulfoxides 1a to 1k were obtained by low-temperature oxidation of sulfides 6a to 6k with m-chloroperbenzoic acid in chloroform (4,23). Antibiotic and EPI susceptibilities of the S. aureus strains.…”

Section: Chemicalmentioning

confidence: 99%

Synthesis of Omeprazole Analogues and Evaluation of These as Potential Inhibitors of the Multidrug Efflux Pump NorA of Staphylococcus aureus

Vidaillac

Guillon

Arpin³

et al. 2007

Antimicrob Agents Chemother

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A series of 11 pyrrolo[1,2-a]quinoxaline derivatives, 1a to 1k, sharing structural analogies with omeprazole, a eukaryotic efflux pump inhibitor (EPI) used as an antiulcer agent, was synthesized. Their inhibitory effect was evaluated using Staphylococcus aureus strain SA-1199B overexpressing NorA. By determinations of the MIC of norfloxacin in the presence of these EPIs devoid of intrinsic antibacterial activity and used at 128 g/ml, and by the checkerboard method, compound 1e (MIC decrease, 16-fold; fractional inhibitory concentration index [⌺FIC], 0.18) appeared to be more active than compounds 1b to 1d, reserpine, and omeprazole (MIC decrease, eightfold; ⌺FIC, 0.31), followed by compounds 1a and 1f (MIC decrease, fourfold; ⌺FIC, 0.37) and 1g to 1k (MIC decrease, twofold; ⌺FIC, 0.50 to 0.56). By time-kill curves combining norfloxacin (1/4 MIC) and the most efficient EPIs (128 g/ml), compound 1e persistently restored the bactericidal activity of norfloxacin (inoculum reduction, 3 log 10 CFU/ml at 8 and 24 h), compound 1f led to a delayed but progressive decrease in the number of viable cells, and compounds 1b to 1d and omeprazole acted synergistically (inoculum reduction, 3 log 10 CFU/ml at 8 h but further regrowth), while compound 1a and reserpine slightly enhanced norfloxacin activity. The bacterial uptake of norfloxacin monitored by high-performance liquid chromatography confirmed that compounds 1a to 1f increased antibiotic accumulation, as did reserpine and omeprazole. Since these EPIs did not disturb the ⌬ and ⌬pH, they might directly interact with the pump. A structure-activity relationships study identified the benzimidazole nucleus of omeprazole as the main structural element involved in efflux pump inhibition and highlighted the critical role of the chlorine substituents in the stability and efficiency of compounds 1e to 1f. However, further pharmacomodulation is required to obtain therapeutically applicable derivatives.

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Section: Chemicalmentioning

confidence: 99%

Synthesis of Omeprazole Analogues and Evaluation of These as Potential Inhibitors of the Multidrug Efflux Pump NorA of Staphylococcus aureus

Vidaillac

Guillon

Arpin³

et al. 2007

Antimicrob Agents Chemother

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“…Additionally, the 2-alkylthiobenzimidazoles [4] and their corresponding de- rivatives have been shown to be proton-pump inhibitors [5], and anti-ulcer [6] and anti-virals agents [7]. Recently, we have reported that the ambident synthon derived from ethyl 2-(1H-benzimidazol-2-yl)-3-dimethylamino-acrylate 1a [8, 9a] was used for the synthesis of 1-oxo-1,2-dihydropyrimido-[1,6-a]-benzimidazole-4-carboxylate [8,9a], according to a regioselective aza-annulation with good yields.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective synthesis of (2E) 3-amino-2-(1H-benzimidazol-2-yl)acrylate and symmetric bisacrylates by transamination reactions

et al. 1999

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“…[1] The recent literature revealed that pyrimidine nucleus has a considerable attention in producing less ulcerogenic index. [23] In the view of above reports, it was thought worthwhile to design a novel framework by which the benzimidazole derivatives were linked with the pyrimidine nucleus and evaluated their anti-ulcer activity.…”

mentioning

confidence: 99%

Synthesis and PASS-assisted in silico approach of some novel 2-substituted benzimidazole bearing a pyrimidine-2, 4, 6(trione) system as mucomembranous protector

Mathew¹,

Suresh

Anbazhagan³

2013

J Pharm Bioall Sci

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Purpose:The present paper demonstrates the utility of PASS computer-aided program and makes a clear comparison of predicted and observed pharmacological properties of some novel 5-[(2E)-1-(1H-benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene] pyrimidine-2, 4, 6 (1H, 3H, 5H)-triones (5a–f).Materials and Methods:The synthesis of the titled derivatives were achieved by the reaction between 2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-ones (4a–f) and barbituric acid in the presence of catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1HNMR and mass spectra analysis. All the newly synthesized compounds were screened for their antiulcer activity in the pylorus-ligated rats.Results:Compounds 5b, 5e and 5c showed a percentage protection of (69.58, 69.56 and 67.17 at a dose of 50 mg/kg b.w.) when compared to standard omeprazole (77.37%, 2 mg/kg b.w.).Conclusion:Scanning of stomach specimens using electron microscope revealed that the mice treated with standard and synthetic derivatives had no injury observed in stomach mucosa, which is identical to that of the control animal.

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Anti-secretory and anti-ulcer activities of some new 2-(2-pyridylmethyl-sulfinyl)-benzimidazoles

Cited by 40 publications

References 14 publications

Synthesis of Omeprazole Analogues and Evaluation of These as Potential Inhibitors of the Multidrug Efflux Pump NorA of Staphylococcus aureus

Synthesis of Omeprazole Analogues and Evaluation of These as Potential Inhibitors of the Multidrug Efflux Pump NorA of Staphylococcus aureus

Stereoselective synthesis of (2E) 3-amino-2-(1H-benzimidazol-2-yl)acrylate and symmetric bisacrylates by transamination reactions

Synthesis and PASS-assisted in silico approach of some novel 2-substituted benzimidazole bearing a pyrimidine-2, 4, 6(trione) system as mucomembranous protector

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