Based on a broad spectrum of biological activities of rhodanines, we synthesized aromatic amides and esters of 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (rhodanine-3-acetic acid) via carbodiimide- or PCl3-mediated coupling. Both esters and amides were investigated for their in vitro inhibitory potency and selectivity against acetylcholinesterase (AChE) from electric eel and butyrylcholinesterase (BChE) from equine serum using Ellman's spectrophotometric method. The derivatives exhibited mostly a moderate activity against both cholinesterases. IC50 values for AChE were in a closer concentration range of 24.05-86.85μM when compared to BChE inhibition (7.92-227.19μM). The esters caused the more efficient inhibition of AChE than amides and parent acid. The esterification and amidation of the rhodanine-3-acetic acid increased inhibition of BChE, even up to 26 times. Derivatives of 4-nitroaniline/phenol showed the activity superior to other substituents (H, Cl, CH3, OCH3, CF3). Rhodanines produced a balanced inhibition of both cholinesterases. Seven derivatives produced the more potent inhibition of AChE than rivastigmine, a clinically used drug; additional three compounds were comparable. Two amides exceeded inhibitory potency of rivastigmine towards BChE. Importantly, this is the first evidence that rhodanine-based compounds are able to inhibit BChE.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• butyrylcholinesterasa krev   metabolismus   MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   farmakologie   MeSH
• Electrophorus MeSH
• koně MeSH
• molekulární struktura MeSH
• rhodanin chemická syntéza   chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Twenty-four 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (rhodanine-3-acetic acid)-based amides, esters and 5-arylalkylidene derivatives were synthesized, characterized and evaluated as potential antimicrobial agents against a panel of bacteria, mycobacteria and fungi. All of the derivatives were active against mycobacteria. N-(4-Chlorophenyl)-2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetamide demonstrated the highest activity against Mycobacterium tuberculosis with minimum inhibitory concentrations (MIC) of 8-16μM. Non-tuberculous mycobacteria were the most susceptible to 2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetic acids (MIC values ⩾32μM). The highest antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus exhibited 4-(trifluoromethyl)phenyl 2-(4-oxo-2-thioxothiazolidin-3-yl)acetate (MIC⩾15.62μM). Several structure-activity relationships were identified. The activity against Gram-negative and fungal pathogens was marginal.

• MeSH
• antiinfekční látky farmakologie   MeSH
• Candida účinky léků   MeSH
• grampozitivní bakterie účinky léků   MeSH
• kyselina octová chemie   MeSH
• magnetická rezonanční spektroskopie s uhlíkem 13C MeSH
• methicilin rezistentní Staphylococcus aureus účinky léků   MeSH
• mikrobiální testy citlivosti MeSH
• protonová magnetická rezonanční spektroskopie MeSH
• rhodanin chemie   farmakologie   MeSH
• spektrofotometrie infračervená MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Aldose reductase, the first enzyme of the polyol pathway represents a key drug target in therapy of diabetic complications. In this study a series of six novel rhodanine based inhibitors of aldose reductase was designed, synthesized, and tested for their ability to inhibit aldose reductase and for selectivity relative to structurally related aldehyde reductase. Aldose reductase inhibitory activities of the compounds were characterized by the IC50 values ranging from 2000 nM to 20 nM. The values of selectivity factors relative to aldehyde reductase were decreasing in the same array from 24 to 5. In silico docking into the inhibitor binding site of aldose reductase revealed a specific binding pattern of the compounds comprising interaction of the deprotonated 4-hydroxybenzylidene group with the anion-binding sub-pocket of aldose reductase, creating a strong H-bond and charge interactions. Predicted pH-distribution profiles of the novel compounds into octanol, supported by experimentally determined distribution ratios, favour drug uptake at the physiological pH, as a result of the presence of the low-acidic phenolic group, instead of the more acidic carboxymethyl functional group.

• MeSH
• aldehydreduktasa MeSH
• inhibitory enzymů * chemie   MeSH
• rhodanin * farmakologie   chemie   MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH

The constant increase in the resistance of pathogenic bacteria to the commonly used drugs so far makes it necessary to search for new substances with antibacterial activity. Taking up this challenge, we obtained a series of rhodanine-3-carboxyalkyl acid derivatives containing 2- or 3- or 4-pyridinyl moiety at the C-5 position. These compounds were tested for their antibacterial and antifungal activities. They showed activity against Gram-positive bacteria while they were inactive against Gram-negative bacteria and yeast. In order to explain the relationship between the activity of the compounds and their structure, for selected derivatives crystal structures were determined using the X-ray diffraction method. Modeling of the isosurface of electron density was also performed. For all tested compounds their lipophilicity was determined by the RP-TLC method and by calculation methods. On the basis of the carried-out research, it was found that the derivatives with 1.5 N···S electrostatics interactions between the nitrogen atom in the pyridine moiety and the sulfur atom in the rhodanine system showed the highest biological activity.

• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• gramnegativní bakterie MeSH
• grampozitivní bakterie MeSH
• mikrobiální testy citlivosti MeSH
• rhodanin * chemie   farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• játra metabolismus   MeSH
• krysa rodu rattus MeSH
• kyanidy moč   MeSH
• nitrily krev   metabolismus   MeSH
• xenobiotika MeSH
• Check Tag
• krysa rodu rattus MeSH

• Publikační typ
• abstrakt z konference MeSH

• Publikační typ
• abstrakt z konference MeSH

A series of rhodanine derivatives was prepared. The synthetic approach, analytical and spectroscopic data of all synthesized compounds are presented. Lipophilicity of all the discussed rhodanine derivatives was analyzed using the RP-HPLC method. The compounds were tested for their ability to inhibit photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts and reduce chlorophyll content in freshwater alga Chlorella vulgaris. Structure-activity relationships between the chemical structure, physical properties and biological activities of the evaluated compounds are discussed. For majority of the tested compounds the lipophilicity of the compound and not electronic properties of the R1 substituent were decisive for PET-inhibiting activity. The most potent PET inhibitor was (5Z)-5-(4-bromobenzylidene)-2-thioxo-1,3-thiazolidin-4-one (IC(50) = 3.0 μmol/L) and the highest antialgal activity was exhibited by (5Z)-5-(4-chlorobenzylidene)-2-thioxo-1,3-thiazolidin-4-one (IC(50) = 1.3 μmol/L).

• MeSH
• Chlorella vulgaris účinky léků   metabolismus   MeSH
• chloroplasty účinky léků   metabolismus   MeSH
• fotosyntéza účinky léků   MeSH
• hydrofobní a hydrofilní interakce MeSH
• nukleární magnetická rezonance biomolekulární MeSH
• rhodanin analogy a deriváty   chemická syntéza   farmakologie   MeSH
• Spinacia oleracea účinky léků   metabolismus   MeSH
• transport elektronů účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Metabolismus rhodaninu draselného, guanidium rhonadinu a nově připraveného rhodanoglukosátu draselného. Řešena otázka, působí-li jejich deriváty v organismu jako celé molekuly či jako anionty. 1) Rhodanoglukosát draselný|působí jako celá molekula. 2) Rhodanidový ion se váže na albuminy plasmy. 3) Po podání některé z těchto sloučenin nedoznaly bílkoviny krevní viskosimetricky patologických změn, thermostabilizační účinek byl však výrazný

• MeSH
• antihypertenziva MeSH
• hypertenze MeSH
• rhodanin analogy a deriváty   metabolismus   MeSH
• Publikační typ
• srovnávací studie MeSH

Some [(5Z)-(5-arylalkylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-yl)]acetic acids were prepared as potential antifungal compounds. The general synthetic approach to all synthesized compounds is presented. Lipophilicity of all the discussed rhodanine-3-acetic acid derivatives was analyzed using a reversed phase high performance liquid chromatography (RP-HPLC) method. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C(18) stationary RP column. The RP-HPLC retention parameter log k (the logarithm of the capacity factor k) is compared with log P values calculated in silico. All compounds were evaluated for antifungal effects against selected fungal species. Most compounds exhibited no interesting activity, and only {(5Z)-[4-oxo-5-(pyridin-2- ylmethylidene)-2-thioxo-1,3-thiazolidin-3-yl]}acetic acid strongly inhibited the growth of Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I and Trichosporon asahii 1188.

• MeSH
• acetáty farmakologie   chemická syntéza   chemie   MeSH
• antifungální látky farmakologie   chemická syntéza   chemie   MeSH
• Candida glabrata účinky léků   MeSH
• Candida tropicalis účinky léků   MeSH
• rhodanin analogy a deriváty   farmakologie   chemická syntéza   chemie   MeSH
• thiazolidiny farmakologie   chemická syntéza   chemie   MeSH
• Trichosporon účinky léků   MeSH
• Publikační typ
• práce podpořená grantem MeSH