Substituted phenethylamine-based ß-lactam derivatives: Antimicrobial, anticancer, and ß-lactamase inhibitory properties.

In this study, a series of novel ß-lactam derivatives were synthesized with yields ranging from 41 % to 91 %, and their antimicrobial activities were investigated against bacterial and fungal isolates that cause nosocomial infections. The results revealed that the novel ß-lactam derivatives, especially compound 19, showed antibacterial activities ranging from 0.98 to 250 µg/mL. In contrast, the compounds showed no antifungal activity against fungal isolates. Following that, biochemical (Nitrocefin) investigation of compounds with antibacterial activity was carried out, as well as their effects on the ß-lactamase enzyme. According to the results, the compounds inhibited the ß-lactamase enzyme against bacterial isolates. Furthermore, the anticancer activity and toxicity profiles of ß-lactam derivatives were also studied against colorectal cancer (Caco-2), the most common type of cancer, and non-human dermal fibroblast cell line. The results revealed that compound 19 was shown the best anticancer activity and lowest toxicity profile among other compounds. Therefore, these compounds, especially compound 19, could be useful in the treatment of colorectal cancer and related nosocomial infections. Furthermore, the potential of being an antibiotic can be put forward by investigating the resistant mechanism and further pharmacological studies.

Hematotoxic, oxidative and genotoxic damage in rainbow trout (Oncorhynchus mykiss) after exposure to 3-benzoylpyridine.

Pyridine is a basic heterocyclic organic compound. The pyridine ring is present in many important compounds, including agricultural chemicals, medicines and vitamins. Due to their widespread industrial use, bioaccumulation and non-target toxic effects are being considered as a great risk to human and environmental health. In this study, we aimed to evaluate the hematological, oxidative and genotoxic damage potentials by different concentrations (1, 1.5, and 2 g/L) of the ketone 3-Benzoylpyridine (3BP) on rainbow trout (Oncorhynchus mykiss). Alterations in the biomarker levels of oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), apoptosis (Caspase-3), malondialdehyde (MDA) as well as antioxidant enzyme activities including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), myeloperoxidase (MPO), paraoxonase (PON), and arylesterase (AR) were assessed in brain, liver, gill and blood tissues. Acetylcholinesterase (AChE) activity was also determined in brain tissue. In addition, we analyzed micronucleus (MN) rates and hematological indices of total erythrocyte count (RBC), total leukocyte count (WBC), hemoglobin (Hb), hematocrit (Hct), total platelet count (PLT), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), and mean cell volume (MCV) in blood. LC50-96h value of 3BP was calculated as 5.2 g/L from the data obtained. A significant decrease in brain AChE activity was determined in clear time and dose dependent manners. While SOD, CAT, GPx, PON, and AR levels were decreased, MDA, MPO, 8-OHdG and Caspase-3 levels were increased in all tissues (p < 0.05). Again, the 3BP led to increases of MN formation at all applied concentrations in the rates of between 45.4 and 72.7%. Significant differences (p < 0.05) were found out in between all studied hematology parameters between 3BP-exposed and the control fish. In conclusion, ours study firstly indicated that the treatment doses of 3BP induced distinct hematological and oxidative alterations as well as genotoxic damage in rainbow trout.

Design, synthesis, characterization, and biological evaluation of nicotinoyl thioureas as antimicrobial and antioxidant agents.

Addressed herein a series of thioureas starting from various amines and nicotinic acid have been synthesized. Notably, thiourea based scaffolds are increasingly employed in medicinal chemistry owing to their tunable physicochemical and structural properties. As well-known from the literature, the pyridine ring contains various biological properties, especially antimicrobial activity. Therefore, we performed the synthesis of biologically important thiourea derivatives containing pyridine ring. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR and FT-IR. In the second part of the study, newly synthesized compounds were also tested in order to demonstrate their antimicrobial and antioxidant properties. All compounds exhibited moderate activity against all tested bacteria known to cause nosocomial infections, which have acquired resistance to many antibiotics, as compared to the standard antibiotics and also strong antioxidant properties. Therefore, they can be evaluated as possible seeds of agents in the treatment of bacterial infections and many health problems related to aging such as cancer, and neurodegenerative diseases.

Synthesis and Anticancer Activity of Novel Ureas and Sulfamides Incorporating 1-Aminotetralins.

BACKGROUND AND AIMS: In the present study, a series of ureas and sulfamides derived from 1-aminotetralins were synthesized. For this purpose, urea and sulfamide analogues were synthesized from the reactions of substituted 1-aminotetralins with N,N-dimethylcarbamoyl chloride and N,N-dimethylsulfamoyl chloride. The anticancer activity of newly synthesized compounds was tested against human U-87MG glioblastoma and PC-3 prostate cancer cell lines. Cytotoxicity was examined using MTT and LDH release assays. RESULTS: The obtained data revealed that tested compounds showed a variable degree of cytotoxic activity against the tested cell lines. 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-1,1-dimethylurea (9) and 3-(6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-1,1-dimethylurea (10) proved to be the most active cytotoxic members in this study. CONCLUSIONS: These two compounds could be considered as possible anticancer agents.

Antioxidant Activity, Acetylcholinesterase, and Carbonic Anhydrase Inhibitory Properties of Novel Ureas Derived from Phenethylamines.

A series of ureas derived from phenethylamines were synthesized and evaluated for human carbonic anhydrase (hCA) I and II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzyme inhibitory activities and antioxidant properties. The ureas were synthesized from the reactions of substituted phenethylamines with N,N-dimethylcarbamoyl chloride; then, the synthesized compounds were converted to their corresponding phenolic derivatives via O-demethylation. hCA I and II were effectively inhibited by the newly synthesized compounds, with Ki values in the range of 0.307-0.432 nM for hCA I and 0.149-0.278 nM for hCA II. On the other hand, the Ki parameters of these compounds for AChE and BChE were determined in the range of 0.129-0.434 and 0.095-0.207 nM, respectively. Phenolic ureas also showed good antioxidant activities.

Acetylcholinesterase and carbonic anhydrase inhibitory properties of novel urea and sulfamide derivatives incorporating dopaminergic 2-aminotetralin scaffolds.

In the present study a series of urea and sulfamide compounds incorporating the tetralin scaffolds were synthesized and evaluated for their acetylcholinesterase (AChE), human carbonic anhydrase (CA, EC 4.2.1.1) isoenzyme I, and II (hCA I and hCA II) inhibitory properties. The urea and their sulfamide analogs were synthesized from the reactions of 2-aminotetralins with N,N-dimethylcarbamoyl chloride and N,N-dimethylsulfamoyl chloride, followed by conversion to the corresponding phenols via O-demethylation with BBr3. The novel urea and sulfamide derivatives were tested for inhibition of hCA I, II and AChE enzymes. These derivatives exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values of 2.61-3.69nM against hCA I, 1.64-2.80nM against hCA II, and in the range of 0.45-1.74nM against AChE. In silico techniques such as, atomistic molecular dynamics (MD) and molecular docking simulations, were used to understand the scenario of the inhibition mechanism upon approaching of the ligands into the active site of the target enzymes. In light of the experimental and computational results, crucial amino acids playing a role in the stabilization of the enzyme-inhibitor adducts were identified.

Synthesis and inhibitory properties of some carbamates on carbonic anhydrase and acetylcholine esterase.

A series of carbamate derivatives were synthesized and their carbonic anhydrase I and II isoenzymes and acetylcholinesterase enzyme (AChE) inhibitory effects were investigated. All carbamates were synthesized from the corresponding carboxylic acids via the Curtius reactions of the acids with diphenyl phosphoryl azide followed by addition of benzyl alcohol. The carbamates were determined to be very good inhibitors against for AChE and hCA I, and II isoenzymes. AChE inhibition was determined in the range 0.209-0.291 nM. On the other hand, tacrine, which is used in the treatment of Alzheimer's disease possessed lower inhibition effect (Ki: 0.398 nM). Also, hCA I and II isoenzymes were effectively inhibited by the carbamates, with inhibition constants (Ki) in the range of 4.49-5.61 nM for hCA I, and 4.94-7.66 nM for hCA II, respectively. Acetazolamide, which was clinically used carbonic anhydrase (CA) inhibitor demonstrated Ki values of 281.33 nM for hCA I and 9.07 nM for hCA II. The results clearly showed that AChE and both CA isoenzymes were effectively inhibited by carbamates at the low nanomolar levels.

The human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibition effects of trimethoxyindane derivatives.

Carbonic anhydrases (CAs, EC 4.2.1.1) had six genetically distinct families described to date in various organisms. There are 16 known CA isoforms in humans. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. Acetylcholine esterase (AChE. EC 3.1.1.7) is a hydrolase that hydrolyzes the neurotransmitter acetylcholine relaying the signal from the nerve. In this study, some trimethoxyindane derivatives were investigated as inhibitors against the cytosolic hCA I and II isoenzymes, and AChE enzyme. Both hCA isozymes were inhibited by trimethoxyindane derivatives in the low nanomolar range. These compounds were good hCA I inhibitors (Kis in the range of 1.66-4.14 nM) and hCA II inhibitors (Kis of 1.37-3.12 nM) and perfect AChE inhibitors (Kis in the range of 1.87-7.53 nM) compared to acetazolamide as CA inhibitor (Ki: 6.76 nM for hCA I and Ki: 5.85 nM for hCA II) and Tacrine as AChE inhibitor (Ki: 7.64 nM).

Mutagenic assessment of three synthetic pyridine-diaryl ketone derivatives.

Nowadays, there are increasing numbers of studies about synthetic chemicals according to the supply demands of bioactive chemicals. The current study aims to investigate genotoxic potential of bioactive synthetic pyridine compounds, phenyl-3-pyridinylmethanone (1), p-tolyl-3-pyridinylmethanone (2), and 4-methoxyphenyl-3-pyridinylmethanone (3), using Ames/Salmonella and Escherichia coli WP2 bacterial reversion mutagenicity test systems. The mutant bacterial tester strains sodium azide-sensitive Salmonella typhimurium TA1535, 9-aminoacridine-sensitive S. typhimurium TA1537, and N-methyl-N'-nitro-N-nitrosoguanidine-sensitive E. coli WP2uvrA were used to detect the mutagenic potential of the test compounds. The results indicated that none of the test substances showed significant mutagenic activity on S. typhimurium TA1535, TA1537, and E. coli WP2uvrA bacterial strains up to 1 µg/plate concentrations.