Effective asymmetric Michael addition of anthrone to nitroalkenes using chiral tetraoxacalix[2]arene[2]triazines as organocatalysts.

Novel chiral secondary amines bearing a tetraoxacalix[2]arene[2]triazine scaffold were created and used for catalytic asymmetric Michael reaction of anthrone with nitroalkenes. The relevant adducts were obtained in good to excellent yields (82%-98%) and enantioselectivities (75%-98%).

Design, synthesis and application of chiral tetraoxacalix[2]arene[2]triazine-based organocatalysts in asymmetric Michael addition reactions.

A novel type of oxacalix[2]arene[2]triazine-based organocatalysts for asymmetric Michael reactions are reported for the first time. Chiral subunits were attached to the heteroatom-bridged calixaromatic platform by a reaction of (R)- and (S)-1-aminotetraline with tetraoxacalix[2]arene[2]triazine in both enantiomeric forms. To evaluate the catalytic efficiency of the novel organocatalysts, isobutyraldehyde reacted with various substituted and unsubstituted aromatic trans-ß-nitrostyrenes in tetrahydrofuran (THF), leading to Michael adducts in excellent yields and enantioselectivites (up to 97% yield and 99% ee).

Enantioselective Michael reaction of anthrone catalyzed by chiral tetraoxacalix[2]arene[2]triazine derivatives.

A highly enantioselective Michael addition reaction of anthrone with nitroalkenes by chiral tetraoxacalix[2]arene[2]triazine catalysts was investigated as a novel topic. The stereoselective conversion progressed smoothly by employing 10 mol% of the catalyst and afforded the corresponding Michael adducts with acceptable to high enantioselectivities (up to 97% ee) and very high yields (up to 96%).

Novel thymol bearing oxypropanolamine derivatives as potent some metabolic enzyme inhibitors - Their antidiabetic, anticholinergic and antibacterial potentials.

A series of classical and newly synthesized thymol bearing oxypropanolamine compounds were synthesized and characterized. Their in vitro antibacterial activity on A. baumannii, P. aeruginosa, E. coli and S. aureus strains were investigated with agar well diffusion method. The results were compared with commercially available drug active compounds. As well as 3a, 3b and 3c have the most significant antibacterial effect among all the tested compounds; approximately all of them have more antibacterial activity than the reference drugs. These novel thymol bearing oxypropanolamine derivatives were effective inhibitors of the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase enzymes (AChE) with Ki values in the range of 463.85-851.05 µM for α-glycosidase, 1.11-17.34 µM for hCA I, 2.97-17.83 µM for hCA II, and 13.58-31.45 µM for AChE, respectively.

Developmental Toxicity of (4S)-2- (4-hydroxy-3-methoxyphenyl) thiazolidine-4-carboxylic acid in Zebrafish ( Danio rerio )

ABSTRACT (4S)-2-(4-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid is new synthesized substance obtained from cysteine and valine. Thiazolidine derivates have important biological responses so scientists work intensively on these compounds in recent years. It is obvious that thiazolidine contained compounds will be used in future in the pharmaceutical industry to treat important diseases. Median lethal concentrations (LC50) for 48 h and 96 h were found as 1.106±0.052 mM and 0.804mM ± 0.102 respectively. According to LC50, exposure doses were determined as control, 0.4 mM, 0.2 mM and 0.1 mM (4S)-2-(4-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid. Developmental toxicity and apoptotic features on zebrafish development were evaluated in this study. The results of this study indicate that (4S)-2-(4-hydroxy-3-methoxyphenyl)thiazolidine-4-carboxylic acid exposure cause developmental defects like pericardial edema, bent spine, tail malformation, blood accumulation, yolk sac edema but on the other hand concentration-dependent decrease in apoptotic rate. Likewise, concentration-dependent decrease in hatching and increase in mortality of embryos were also detected.

Discovery of Potent Carbonic Anhydrase and Acetylcholinesterase Inhibitors: 2-Aminoindan ß-Lactam Derivatives.

ß-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. ß-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that ß-lactams are inhibitors of hCA I, II and AChE. The Ki values of ß-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that ß-lactams (2a-k) inhibit both carbonic anhydrases (CA) isoenzymes and AChE at low nanomolar concentrations.

Synthesis and tyrosinase inhibitory properties of novel isoquinoline urea/thiourea derivatives.

A new series of isoquinoline urea/thiourea derivatives (1-11) were synthesized, and their inhibitory effects on tyrosinase were evaluated. Isoquinoline urea/thiourea derivatives were obtained as a result of the reaction of 5-aminoisoquinoline with isocyanates or isothiocyanates. The result showed that all the synthesized compounds inhibited the tyrosinase enzyme activity. Among the compounds synthesized, 1-(4-chlorophenyl)-3-(isoquinolin-5-yl)thiourea (3) was found to be the most active one (Ki = 119.22 µM), and the inhibition kinetics analyzed using Lineweaver-Burk double reciprocal plots revealed that compound 3 was a competitive inhibitor. We also calculated HOMO-LUMO energy levels, some selected the synthesized compounds (1, 4, 11, 3, 6, 2) using Gaussian software.

In vitro effect of novel ß-lactam compounds on xanthine oxidase enzyme activity.

Carbazole substituted imines (2a-l) were prepared from N-methyl-3-amino carbazole with different aldehydes. The imines compounds undergo (2+2) cycloaddition reactions with in situ ketenes to produce ß-lactam compounds (3a-l). The ß-lactam compounds were tested as inhibitors of the xanthine oxidase (XO) purified from bovine milk. The results show that these compounds exhibit inhibitory effects on XO at low concentrations with IC(50) values ranging from 21.65 to 58.04 µM. The most effective compound for XO was 4-(4-chlorophenyl)-1-(9-ethyl-9H-carbazol-3-yl)-3-phenylazetidin-2-one with IC(50) of 21.65 µM. The lactams investigated here showed effective XO inhibitory effects, in the same range as the clinically used allopurinol.

In vitro inhibition of polyphenol oxidase by some new diarylureas.

A new series of N,N'-diarylureas (1-9) was synthesized. These compounds were investigated as inhibitors of polyphenol oxidase (PPO) which had been purified from banana by an affinity gel comprised of Sepharose 4B-l-tyrosine-p-amino benzoic acid. K(i) values for (1), (2), (3), (5), (6), (7) and (8) were determined as 0.285, 17.97, 0.187, 0.108, 0.063, 0.044 and 0.047 mM, respectively. Thus (2) was by far the most effective inhibitor. Interestingly, (4) and (9) behaved as an activator of PPO in this study.