Microbiological Evaluation of 4-substituted-imidazolidine Derivatives
In the present studies, two series of 4-substituted-imidazolidines (IIIa-i and IIIj,k) were synthesized by reacting different tetrahydro-di-Schiff bases (IIa-i and IIj,k) with p-diethylaminobenzaldehyde/ dimethylaminobenzaldehyde. The title compounds were evaluated for their antibacterial and antifungal actions against some selected microbes. The results of microbiological evaluation revealed that two compounds, 4-(1,3-bis(benzo[d][1,3]dioxol-5-ylmethyl)-4-methylimidazolidin-2-yl)-N,N-diethyl aniline (IIIj), 4-(1,3-bis(benzo[d][1,3]dioxol-5-ylmethyl)-4-methylimidazolidin-2-yl)-N,N-dimethyl aniline (IIIk) were good in their antibacterial as well as antifungal actions. Minimum inhibitory concentration values (MIC) of the compounds are reported.
Synthesis and Biological Evaluation of Novel Substituted-Imidazolidine Derivatives
A series of newer substituted-imidazolidine derivatives 3ak were synthesized and assayed in vivo to investigate their anti-inflammatory, analgesic and antiulcer activity. The results of biological evaluation revealed that the three compounds, 4- (1,3-bis(4-hydroxy-3-methoxybenzyl)-2-imidazolidinyl)phenyldiethylamine (3g), 4-(1,3-bis(3-Ethoxy-4-hydroxybenzyl)-2-imida- zolidinyl)phenyldiethylamine (3h) and 4-(1,3-bis(benzo(d)(1,3)dioxol-5-ylmethyl)-4-methylimidazolidin-2-yl)-N,N-diethyl- benzenamine (3j) were good in their anti-inflammatory and analgesic actions. Additionally these derivatives showed superior GI safety profile as compared to that of the standard drug in terms of low severity index. The results are statistically treated for its significance.
Structure mechanism insights and the role of nitric oxide donation guide the development of oxadiazole-2-oxides as therapeutic agents against schistosomiasis.
Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of individuals worldwide. Current treatment depends on a single agent, praziquantel, raising concerns of emergence of resistant parasites. Here, we continue our explorations of an oxadiazole-2-oxide class of compounds we recently identified as inhibitors of thioredoxin glutathione reductase (TGR), a selenocysteine-containing flavoenzyme required by the parasite to maintain proper cellular redox balance. Through systematic evaluation of the core molecular structure of this chemotype, we define the essential pharmacophore, establish a link between the nitric oxide donation and TGR inhibition, determine the selectivity for this chemotype versus related reductase enzymes, and present evidence that these agents can be modified to possess appropriate drug metabolism and pharmacokinetic properties. The mechanistic link between exogenous NO donation and parasite injury is expanded and better defined. The results of these studies verify the utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious antischistosomal agents.