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In the search for novel hybrid molecules by fusing two biologically active scaffolds into one heteromeric chemotype, we found that hybrids of azithromycin and ciprofloxacin/gatifloxacin 26j and 26l can inhibit the supercoiling activity of E. coli gyrase by poisoning it in a way similar to fluoroquinolones. This may modestly contribute to their potencies, which are equal to ciprofloxacin against constitutively resistant Staphylococcus aureus, whose growth is not inhibited by the presence of macrolides. In contrast, introduction of quinolines (the 3-quinoline 26b and the 6-quinoline 26o) with an optimized rigid spacer at the 6-OH of azithromycin acylides did not exert significant potency against constitutively resistant S. aureus, despite the fact that the quinoline-containing compounds, exemplified by 26o, were as active as telithromycin against susceptible, inducibly- and efflux-resistant pathogens. The novel dual modes of action involving protein synthesis inhibition and poisoning DNA replication may pave the way for restoration of antibacterial activities of the current macrolides against constitutively resistant clinical isolates.
This article was published in the following journal.
Name: European journal of medicinal chemistry
Three macrolides bearing the carbon framework of oxabicyclo[21.3.1]heptacosa-ene-diones (A and B) and oxabicyclo[19.3.1]pentacosa-ene-dione (C) were isolated and characterised from the organic extract...
Classical macrolides containing 14- or 15-membered aglycone lactone rings are basic and widely used antibacterial agents in clinical therapy. Macrolides exert antibacterial effects by blocking the exi...
The emergence of drug resistance has created unmet medical need for the development of new classes of antibiotics. Innovation of new antibacterial agents with new mode of action remains a high priorit...
We have determined the X-ray structure of Ir(pnbi)2(acac) (pnbi = 2-phenanthren-9-yl-1-phenyl-1H-benzimidazole; acac = acetylacetonate), which exhibits a six-membered metallocycle around the Ir center...
Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, ...
There is increasing evidence that obesity is associated with increased urinary oxalate excretion, an important risk factor for calcium oxalate stone formation. By the administration of a c...
Suboptimal use of medications among geriatric patients is well-known problem and leads to medication errors, re-hospitalizations and death. By using a randomized controlled trial (RCT) des...
The purpose of this study is to investigate the utility of the cantharidin-induced skin blister assay for evaluation of the anti-inflammatory effects of macrolides in healthy male voluntee...
Resistance to antibiotics is a major public-health problem and studies linking antibiotic use and resistance have shown an association not a causal effect. Utilizing the newer macrolides, ...
Cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids. Both adrenal and non-adrenal (ovarian + testicular) all steroid hormones are primarily synthesized usi...
A group of macrocyclic compounds formed by chain extension of multiple PROPIONATES and cyclized into a large (typically 12, 14, 16) membered lactone. They are often glycosylated. Many of them are ANTIBIOTICS.
Compounds based on a seven-membered ring fused to a five-membered ring. Heat can rearrange them to NAPHTHALENES which have two fused six-membered rings. They are similar to guaiazulenes which are SESQUITERPENES with a six-membered ring fused to a five-membered ring.
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
Toxic substances isolated from various strains of Streptomyces. They are 20-membered macrolides that inhibit oxidative phosphorylation and mitochondrial ATPases. Venturicidins A and B are glycosides. Used mainly as tools in the study of mitochondrial function.
A closely related group of toxic substances elaborated by various strains of Streptomyces. They are 26-membered macrolides with lactone moieties and double bonds and inhibit various ATPases, causing uncoupling of phosphorylation from mitochondrial respiration. Used as tools in cytochemistry. Some specific oligomycins are RUTAMYCIN, peliomycin, and botrycidin (formerly venturicidin X).
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...