Naturally Occurring and Synthetic Imidazoles: Their Chemistry and Their Biological Activities

Abstract

Invertebrate animals, such as sponges, tunicates and bryozoans, are among the most important sources of biomedically relevant natural products. However, as these animals generally contain only low quantities of the compounds, further pharmacological development is in most cases difficult. There is increasing evidence that many metabolites, in particular polyketides and nonribosomally synthesized peptides, are not produced by the animals themselves but by associated bacterial symbionts. This symbiont hypothesis currently attracts considerable interest, since it implicates that animal-independent production systems based on bacterial fermentation processes could be created. This review gives an overview about recent developments in the research on natural product symbiosis. Different techniques will be discussed that have been employed to pinpoint the actual producer. Since bacterial symbionts are highly fastidious and have been generally resistant to cultivation attempts, emphasis will be laid on culture-independent strategies, such as cell separation approaches and the cloning of biosynthetic genes. These strategies have provided insights into possible sources of several natural products, e.g. the bryostatins, pederin, the onnamides, swinholide A and theopalauamide. Finally, potential techniques for the generation of renewable supplies of symbiont-derived drug candidates will be discussed. Cultivation approaches and the heterologous expression of cloned biosynthesis genes from uncultured symbionts could in future provide access to several important marine drug candidates, including bryostatin 1, halichondrin or ET-743.

Highly Efficient, Environment-Friendly, One-Pot Synthesis of 2-Substituted 4-Formylimidazoles from 4-Acylaminoisoxazoles

“…Further studies in this direction are underway in our laboratory. 1 H and 13 C NMR spectra were obtained in CDCl 3 , CD 3 OD or DMSO-d 6 with TMS as the internal standard on a Varian Unity Inova 400/54 spectrometer. Mass spectra were obtained on a VG Auto Spec 3000 or a Finnigan MAT 90 instrument.…”

“…1 Among the drugs containing an imidazole ring, antifungal drugs such as miconazole and ketoconazole, which block the biosynthetic pathway of ergosterol by the selective inhibition of fungal cytochrome P450, are well known. 2 Some alkaloids also contain an imidazole ring and exhibit many prominent bioactivities such as antimicrobial activity and cytotoxicity.…”

“…2 Some alkaloids also contain an imidazole ring and exhibit many prominent bioactivities such as antimicrobial activity and cytotoxicity. 1,3 Recently, other diverse, interesting bioactivities of imidazoles, such as antikinase IspE activity, 4 tubulin depolymerization inhibition 5 and anti-cyclooxygenase activity, 6 have been demonstrated. Moreover, imidazoles are important precursors of ligands and polymers.…”

The regioselective synthesis of 2-substituted [[(α-aryl-(α′-amino)]methyl]imidazoles through a catalyst-free, one-pot, three-component reaction: scope and limitations

“…Several imidazole ring-containing drugs, such as ketoconazole, itraconazole and clotrimazole, are known to be potent cytochrome P450 (CYP) 3A inhibitors 2 and some imidazole alkaloids manifest antimicrobial, anticryptococcal and cytotoxic activities. 1a,3 Various imidazole derivatives have nitric oxide synthase, 4 5-lipoxygenase inhibitors, 3,5 substrate with CB1, 1b,6 VEGE receptors I and II, 1b,7 and neuropeptide Y antagonistic activities. 1b, 8 Many functionalized imidazoles behave as antibiotics, 9 fungicides, 10 antiulceretics, 11 antidiabetics, antihypertensive and anti-inflammatory agents.…”

Synthesis and structure of metal complexes containing zwitterionic N-hydroxyimidazole ligands

“…The imidazole diazole ring is commonly found in highly significant endogenous biomolecules, including biotin, the essential amino acid histidine, histamine, the pilocarpine alkaloids [1] and other alkaloids, which have been shown to exhibit interesting biological activities such as antimicrobial, anticryptococcal, inhibition of nitric oxide synthase, and cytotoxic activities [2]. Several imidazole derivatives, such as cimetidine, etomidate and ketoconazole, are commonly prescribed pharmaceutical drugs [3,4].…”