ABSTRACT
Lamellarins are polyaromatic alkaloids isolated from marine organisms, including mollusks, tunicates, and sponges. Currently, over 60 structurally distinct natural lamellarins have been reported, and most of them exhibit promising biological activities, such as topoisomerase inhibition, mitochondrial function inhibition, multidrug resistance reversing, and anti-HIV activity. There has also been a significant progress on the synthetic study of lamellarins which has been regularly updated by numerous medicinal chemists as well. This review provides a detailed summary of the synthesis, pharmacology, and structural modification of lamellarins over the past decades.
Subject(s)
Alkaloids , Biological Products , Urochordata , Animals , Structure-Activity Relationship , Drug Resistance, Multiple , Mitochondria , Urochordata/chemistry , Alkaloids/chemistryABSTRACT
A novel approach for developing prodrugs based on masked carboxylic acids is described. Rather than using conventional esterase-based activation, thiazolidinone protecting groups have been identified that can reveal carboxylic acid groups upon activation by hydrogen peroxide. This may prove valuable in the continuing development of prodrug strategies that rely on reactive oxygen species (ROS) as a trigger.
Subject(s)
Hydrogen Peroxide/pharmacology , Prodrugs/chemistry , Thiazolidines/chemistry , Carboxylic Acids/chemistry , Prodrugs/metabolismABSTRACT
Two series of ten chalcones and ten aurones, where ferrocene replaces the C ring and with diverse substituents on the A ring were synthesized. The compounds were tested against two antibiotic-sensitive bacterial strains, E. coli ATCC 25922 and S. aureus ATCC 25923, and two antibiotic-resistant strains, S. aureus SA-1199B and S. epidermidis IPF896. The unsubstituted compound and those with methoxy substitution showed an inhibitory effect on all bacterial strains at minimum inhibitory concentrations ranging between 2 and 32 mg L(-1). For four of these compounds, the effect was bactericidal, as opposed to bacteriostatic. The corresponding organic aurones did not show growth inhibition, underscoring the role of the ferrocene group. The methoxy-substituted aurones and the unsubstituted aurone also showed low micromolar (IC(50)) activity against MRC-5 non-tumoral lung cells and MDA-MB-231 breast cancer cells, suggesting non-specific toxicity.
Subject(s)
Bacteria/drug effects , Benzofurans/chemistry , Benzofurans/pharmacology , Chalcone/chemistry , Chalcone/pharmacology , Ferrous Compounds/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Benzofurans/chemical synthesis , Benzofurans/toxicity , Cell Line, Tumor , Chalcone/chemical synthesis , Chalcone/toxicity , Endpoint Determination , Humans , Metallocenes , Microbial Sensitivity Tests , Time FactorsABSTRACT
We report here the discovery of a potent series of HIV-1 integrase (IN) inhibitors based on the ferrocenyl chalcone difluoridoborate structure. Ten new compounds have been synthesized and were generally found to have similar inhibitory activities against the IN 3' processing and strand transfer (ST) processes. IC(50) values were found to be in the low micromolar range, and significantly lower than those found for the non-coordinated ferrocenyl chalcones and other ferrocene molecules. The ferrocenyl chalcone difluoridoborates furthermore exhibited low cytotoxicity against cancer cells and low morphological activity against epithelial cells.
Subject(s)
Chalcones/chemistry , Chalcones/pharmacology , HIV Infections/drug therapy , HIV Integrase Inhibitors/chemistry , HIV Integrase Inhibitors/pharmacology , HIV Integrase/metabolism , HIV-1/drug effects , Borates/chemistry , Borates/pharmacology , Cell Line, Tumor , Chalcone , HIV-1/enzymology , HumansABSTRACT
The oxidation of the ferrocenyl group of 2'-hydroxyferrocenyl chalcones activates the beta-position of the unsaturated ketone to nucleophilic attack to yield the first examples of ferrocenyl flavones. These compounds are significantly more cytotoxic than their organic analogs on B16 melanoma cells, with IC(50) values in the low micromolar range.
