Selective Chromo-Fluorogenic Chemoprobe for nM Al3+ Recognition: Experimental and Living-Cell Applications.

A rhodamine based chemoprobe BESN was engineered and employed as a selective ''OFF-ON'' chromo-fluorogenic sensor for Al3+ in H2O:MeOH (1:9, v:v). Notable changes in the absorption and emission spectra of BESN were clearly detectable upon the addition of Al3+. Sensitivity and binding mechanism studies demonstrated a good sensing performance of BESN with nanomolar detection limit (130 nM), and it was found to be highly selective towards interfering metal ions. Besides, the binding constant between BESN and Al3+ was found to be 3.19 × 103 M-1. Then, the validation study of BESN for Al3+ was performed based on significant analytical parameters and statistical tests. The binding of Al3+ with BESN (1:1) was probed via infrared, high-resolution mass and emission (Job's plot) spectroscopy measurements. The sensing performance of BESN could make it ideal chemosensor for real applications including vegetable, tuna fish and water samples, also for Smartphone and test-kit applications. The recovery values of the BESN to Al3+ were estimated within a range from 95.13% to 105.30% for water, 94.63% to 109.62% for tuna fish and 94.80% to 109.80% for vegetable samples. Additionally, the BESN has very low cytotoxicity and was triumphantly utilized for the recognition of Al3+ in living-cells.

Catalytic Performance of Chiral Tetraaza-Bridged Calix[4]arene[2]triazine Derivatives for Enantioselective Michael Reactions.

Novel chiral tetraaza-bridged calix[4]arene[2]triazine-based organocatalysts were synthesized and used for catalytic asymmetric Michael reaction of acetylacetone to various aromatic nitrostyrenes. Chiral subunits (R)- and (S)-1,2,3,4-tetrahydro-1-naphthylamine were attached to the tetraaza-bridged calix[4]arene[2]triazine platform in both enantiomeric forms. The R configuration of the major enantiomer of the Michael product was obtained when 3a was used as catalyst, and the S configuration was obtained when 3b was used as catalyst. This indicated that the configuration of the Michael product was controlled by the chiral calixarene moiety. The Michael adducts were obtained in excellent yields (91%) and enantioselectivities (98%).

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).

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.

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.

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.

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.

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%).

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.

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.