Activity Of New Derivatives Research Articles

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines.

The heterocyclic core of imidazo[1,2-a]pyrimidine was formed in satisfactory yields as a result of the interaction of the readily available 2-aminoimidazole with N-substituted maleimides or N-arylitaconimides. The mechanism of the studied processes was postulated basing on experimental data, HPLC-MS analysis of reaction mixtures, and quantum chemical calculations. Molecular docking results of the obtained imidazo[1,2-a]pyrimidines, when compared with voriconazole, a drug already in clinical use, suggest that they may possess antifungal activity against Candida albicans.

Synthesis and neurotropic activity of new derivatives of some amino acid hydantoins and their lithium salts

Synthesis and neurotropic activity of new derivatives of some amino acid hydantoins and their lithium salts

Synthesis and Preliminary Biological study of New Chalcone Derivatives Containing Isoxazoline Moiety

In this research work, synthesis, antimicrobial and antioxidant bioactivity of a chain of compounds having unsaturated ketones bond and isoxazoline moiety have been described. New chalcone derivatives containing isoxazoline moiety have been synthesized. Generally, Chalcones are unsaturated ketones bearing (-CO-CH=CH-) as reactive ketoethylenic group that give the bright yellow colored compounds due to this chromophore group. Firstly, chalcones (IIa-d) have been prepared by cyclocondensation (Claisen-Schmidt condensation) of triphenyl aminobenzaldehyde with different substituted acetophenone in ethyl alcohol to produce a series of chalcones compounds with bright yellow colored as a starting material,. The next step involving the novel chalcones (IIa-d) reacted with hydroxylamine hydrochloride afforded a new isoxazoline compounds (IIIa-d) in basic medium. The prepared compounds were fully characterized by melting points, FTIR, 1H-NMR spectroscopy, 13 C-NMR for some compounds and CHNS techniques. The reactions have been monitored by TLC (Thin Layer Chromatography) technique. The synthesised compound IId showed significant bioactivity against the gram-negative bacteria species. Also, the antioxidant activity of the some new synthesized compounds was evaluated and determined against the DPPH radical (1.1-diphenyl-2-picrylhydrazyl) and compared to that of a standard natural antioxidant, Ascorbic acid, compound IIb showed higher antioxidant activity by using the free radical DPPH. The outcomes of investigation enhanced the activity of new derivatives as antimicrobial reagent.

The study of antidepressant properties of new 1,2,3-triazolo-1,4-benzodiazepine derivatives

Anxiety-depressive disorders are among the most common mental health conditions and often cause significant functional impairment, affecting a person’s quality of life. Research conducted in recent years indicate the importance of studying and searching for new substances based on benzodiazepines, in particular triazolobenzodiazepines, for the treatment of anxiety states and disorders, as well as determining the presence of other biological activities of these compounds. Aim. To study the antidepressant activity of new derivatives of 1,2,3-triazolo-1,4-benzodiazepines in the Porsolt forced swim and tail suspension tests. Materials and methods. The antidepressant activity of new 1,2,3-triazolo-1,4-benzodiazepine derivatives under the code MA-252, MA-253, MA-254, MA-255 and MA-261 was studied in the Porsolt forced swim and tail suspension tests. The following behavioral reactions, such as the latent period of the first immobility (more than 5 seconds), the total duration of immobility (staying in a stationary state), the number of immobile episodes, were recorded. Results and discussion. During the study, a decrease in the total duration of immobility, the main indicator of “despair” of animals, and an increase in the latent period of the first immobility were monitored. It may indicate the manifestation of antidepressant properties of new 1,2,3-triazolo-1,4-benzodiazepine derivatives. The indicator of the antidepressant activity in groups of animals administered MA-253, MA-254 and MA-255 derivatives in all doses was higher among the groups studied. The depression index was the lowest when MA-253 and MA-254 derivatives were used in the dose of 1 mg/kg, and was not statistically significantly different from that in the group receiving imipramine in the dose of 25 mg/kg. According to the results of the tail suspension test, 1,2,3-triazolo-1,4-benzodiazepine derivatives MA-253, MA-254 and MA-255 showed a significant decrease in the total duration of immobilization by 69.4 %, 47.1 % and 33.1 %, respectively, in relation to the control group (p<0.05), as well as an increase in the latent period of the onset of the first immobility episode by several times. Conclusions. A decrease in the duration of immobility in mice injected with 1,2,3-triazolo-1,4-benzodiazepine derivatives gives grounds to draw a conclusion that animals develop a state of “behavioral despair” and exhibit antidepressant properties.

Studying the mechanism of action of new derivatives of quinoxalin-1,4-dioxide on the model organism Mycobacterium smegmatis

According to the World Health Organization (WHO), antibiotic resistance is currently one of the most serious threats to human health, food security, and development. Tuberculosis (TB) remains one of the deadliest bacterial diseases. The primary challenge in treating tuberculosis infection is the emergence of strains with multidrug resistance (MDR) to 4-9 drugs. The emergence of bacterial strains with MDR is a consequence of patients’ insufficient adherence to treatment, interrupted therapy, improperly prescribed courses of chemotherapy, and, according to recent data, the accumulation of antibiotics in the environment, which can activate the natural drug resistance system in bacteria. The consequences of MDR to antibiotics include prolonged hospitalizations, increased medical expenses, and mortality. Therefore, the task is to develop new effective antibacterial agents with novel mechanisms to reduce the emergence of bacterial resistance. In this study, we investigated the mechanisms of action of new promising antimycobacterial derivatives of quinoxalin-1,4-dioxide on the model organism Mycobacterium smegmatis .

Green synthesis and investigation of antioxidant and antibacterial activity of new derivatives of chromenoazepines employing CuO/TiO2@MWCNTs.

The synthesis of novel, high-yield derivatives of chromenoazepine was investigated in this work. CuO/TiO2@MWCNTs was used as a nanocatalyst in a multicomponent reaction involving 4-aminocumarine, activated acetylenic chemicals, and alkyl bromide in room temperature water to create these novel compounds. Using MCRs of 4-aminocumarine, isothiocyanate, and alkyl bromide in the presence of CuO/TiO2@MWCNTs as nanocatalysts in room-temperature water, chromenothiazepines were synthesized under comparable conditions. The freshly synthesized azepine exhibits antioxidant activity since its NH group has undergone two evaluation processes. Additionally, using two types of Gram-negative bacteria in a disk distribution procedure, the antibacterial activity of recently developed azepines was evaluated, and these compounds also inhibited the growth of Gram-positive bacteria. This method's benefits include quick reaction times, large product yields, and straightforward catalyst and product separation through easy steps.

Antidyskinetic activity of new derivatives of inydazol-4,5-dicarbonic acid in a parkinsonism experimental model due to administration of 6-hydroxydopapine

BACKGROUND: Levodopa therapy currently remains the clinical method of choice for patients with Parkinsons disease. However, in the late stages of the disease, approximately 80% of patients receiving treatment developed levodopa-induced dyskinesia. The studied substances are derivatives of imidazole-4,5-dicarboxylic acid. Their pharmacological effect is produced due to interaction with the recognition site of NMDA receptor, which, together with their high efficiency, implies that they are safer than previously available drugs in this pharmacological group.
 AIM: To study the antidyskinetic effect of IEM2295 and IEM2296 derivatives of imidazole-4,5-dicarboxylic acid.
 MATERIALS AND METHODS: The model is based on the toxic effect of 6-hydroxydopamine on rat brain tissue. The first (control) group of rats received injections of only Levodopa and Benserazide, the second group received injections of Levodopa, Benserazide, and the test substance IEM2295, and the third group received injections of Levodopa, Benserazide and the test substance IEM2296. Each group was evaluated based on three criteria: motor function violations, limb dyskinesia, and axial and chewing dyskinesia. The severity of motor functions was graded on a scale of 0 to 4 points at 35, 70, 105, and 140 minutes after injection of the above substances, where 0 and 4 represent the absence and most pronounced degree of pathological movements, respectively.
 RESULTS: The result analysis showed that the greatest effect on reducing the severity of limb dyskinesia, axial dyskinesia, and chewing dyskinesia in rats was observed at 105 and 140 minutes after injections of the studied substances. Statistically significant differences between the control group and rats receiving injections of the studied substances were revealed at all the time points for limb dyskinesia; i.e., at 35, 105, and 140 minutes for axial dyskinesia and at 105 and 140 minutes for chewing dyskinesia.
 CONCLUSIONS: In the experimental model of parkinsonism, IEM2295 and IEM2296 show antiparkinsonian and antidyskinetic activity because they reduce the severity of motor function disorders in rats with levodopa-induced dyskinesia. The results indicate the prospects for continued development of these substances and further research for effective and safe antiparkinsonian agents among compounds of this class.

Evaluation of the analgesic activity of new derivatives of aryl propionic acid on gastric male mice

This study focused on the recent synthesis of new compounds from aryl propionic acid derivatives compared to naproxen. The present study aimed to investigate the safety and efficiency of the new derivatives in improving analgesic effects and reducing adverse effects via modifying its chemical structure by adding new functional groups. The new compounds were characterized, and evaluate their pharmacodynamic effects. The analysis and characterization of new compounds were by 1HMNR and FT-IR spectrum. The investigation of the adverse effect after 5 days of remedy with 20 mg/kg daily administered with naproxen derivatives to the healthy male albino mice (25-30 g) for analgesic activity using the hot plate method. Mice were parted into 5 groups, consisting of the control group and 4 groups that administered naproxen or derivatives of aryl propionic acid (E, H, D1 and D2). The main tests are done by a hot plate, biochemical, macroscopic, and microscopic inspection. The results confirmed that the new drugs have potent analgesic activity. The results showed that mice administered with D1 expressed less ulcerative effect than parent naproxen, H, E and ethanol. Moreover, the number of lesions was significantly less in the D2 group, while D1-treated mice recorded no evidence of ulcers or hemorrhage in their stomachs after being examined under a dissecting microscope. The study concluded that the new D1 derivative is a compound worthy of research and future clinical applications due to its relatively high efficacy and low adverse effects compared to other derivatives prepared and tested in this study. Keywords: Analgesic, Aryl propionic acid, Naproxen, Acidity

IN SILICO PREDICTION OF BIOLOGICAL ACTIVITY OF BROMO DERIVATIVES OF HYDROACRIDINES

The aim of the work was to establish the spect­rum of biological activity of new derivatives of 9-bromo-1,2,3,4-tetrahydroacridine due to the limi­ted amount of literature data. In silico prediction of selected bromo-derivatives of hydrogenated acridines was performed using the SuperPred 3.0 web resource. The obtained results were compared with the results of prediction of active drugs that contain the acridine cycle in their structure - Tacrine, Amiridine and Amsacrine. Results ≤80% were taken into account. The most promising compound was 9-bromo-1,2,3,4-tetra­hydro­acridine. A common predicted target for bro­mide-hydrogenated acridines and all three drugs is DNA-(apurine or apyrimidine site) lyase with binding probabilities ranging from 82-97.5%. Common predicted targets for 9-bromo-1,2,3,4-tetrahydroacridine derivatives, Tacrine and Amsacrine are butyrylcholinesterase (90.4-98.2%) and transcription factor 1-α (92.02-98.01 %). Cathepsin D, toll-like receptor 8 and glucose transporter are promising common targets for further research, but it should be noted that the probability of binding in these drugs was below 80%. All selected compounds were tested for Lipinski's criteria. In addition, in silico prediction of the acute toxicity of bromo-derivatives of acridine was performed in rats with four types of administration. The safest compound according to the oral method of administration is the compound 9-bromo-2-tert-butyl-1,2,3,4-tetrahyd­ro­ac­ridine (1570 mg/kg), while the compound 9-bromo-1,2 turned out to be more toxic than the others ,3,4-tetrahydroacridine (565.3 mg/kg). The estimated average lethal dose of Tacrine after a single oral dose to rats is 40 mg/kg. The prediction results confirmed the prospects of further research among the class of hydrogenated bromoderivatives of acridines.

Synthesis, Characterization and Study the Biological Activity ofnew Derivatives of 1,3- orazepine containing 1,2,4-Triazoloe ring

Compound [1] is prepared from Esterificition of 4-Nitro benzoic acid. It has been reacted with hydrazine to get compound [2]. 3,5-bis (4-Nitro phenyl)-4-amino -1,2,4-triazole [3] has been synthesized by melting of 4-Nitro benzoic acid hydrizide to cretin temperature. The new series of Schiff bases [4a-f] have been syntheised by reacting compound [3] with different benzaldehydes., These derivatives shows ring closer reaction with phathalic anhydride to obtain 1.3- Oxazepine derivatives [Sa-f]. The syntheised compound were characterized by (IR.UV) spectra, melting points the above reaction were followed by TLC. The biological activities are studied against four different kinds of bacteria .

ОЦЕНКА АНТИНОЦИЦЕПТИВНОЙ АКТИВНОСТИ НОВЫХ ПРОИЗВОДНЫХ Α-ЦИАНОТИОАЦЕТАМИДА НА МОДЕЛИ ОСТРОЙ ВОСПАЛИТЕЛЬНОЙ РЕАКЦИИ

The antinociceptive activity of new derivatives of α-cyanothioacetamide was evaluated in the formalin test, which reflects an acute inflammatory reaction. For the study, a standard model of an acute inflammatory reaction was used: laboratory animals were subplantarly injected with 0.1 ml of 5% formalin (algogen) into the right hind limb. The α-cyanothioacetamide samples studied were injected intragastrically at 1 ml at a dose of 5 mg/kg 1.5 hours before the experiment. The comparison drug was chosen as Analgin JSC "Pharmstandard" at a dose of 7 mg/kg. For one hour after injection, the number of pain reactions was recorded according to the method of 4 types of behavioral response. We have identified the potential antinociceptive activity of new derivatives of α-cyanothioacetamide, which allows them to be used for a detailed study.

Antiproliferative activity of new derivatives of pyrazino[1,2-a]benzimidazole: Integrated cell-based assay and computational studies with divalent magnesium, iron, and copper ions.

Magnesium, iron, and copper are three vital metals that play essential roles in cancer cell proliferation. This study aimed to evaluate the metal chelation of new derivatives of pyrazino[1,2-a]benzimidazole and investigate their antiproliferative properties. The density functional theory method has been employed to evaluate the complexation properties of new synthetic pyrazino[1,2-a]benzimidazole derivatives possessing the 4-OMe, 2,4-dimethyl, and 3,4,5-trimethoxy substitution on N-2 phenyl ring with divalent magnesium, iron, and copper. The free energies for the water-ligand exchange reactions were employed to investigate the thermodynamic stability, water exchange properties, and electronic properties in the gas phase. Natural population analysis was employed to estimate atomic partial charges, second-order interactions between the filled and vacant orbitals, and the occupancies of the metals' valence s, p, and d orbitals. Among pyrazino[1,2-a]benzimidazole derivatives, the 3,4,5-trimethoxy substituted pyrazino[1,2-a]benzimidazole shows better electron donor ability. This compound also reduced proliferation and increased the apoptosis of human glioblastoma cancer cells.

Study of Anti-inflammatory Activity of New Derivative of Indomethacin: A Computational Study

This article presents the synthesis of new derivative from thiodaizole, based on the reaction of Thiosemicarbazide with Indomethacin in the presence of Phosphorus (V) oxychloride as catalyst. COX enzyme is divided to two isoforms COX-1 and COX-2 with similar structure and high sequence identity. The novel Inhibitor used a thiodaizole ring in combination with Indomethacin to reduce the risk of analogs interfering with COX-1’s small hydrophobic tunnel. Furthermore, the absence of a carboxylic group in the new Inhibitor reduces the Inhibitor’s ability to form a salt bridge with Arg120 (Figure 2), preventing the inhibition of the COX-1 enzyme. The aim of this study is to investigate the Anti-inflammatory activity of Indomethacin against the human second isoform of prostaglandin synthase (cyclooxygenase, COX-2). COX-2 enzyme 3D structures (PDB ID: 1CVU) were extracted from the protein databank. The PDB format of Indomethacin and its derivative were prepared by use Discovery Studio 2016 Client. Molecular docking study appeared that the new derivative exhibited better binding energy (-10.9 kcal/mol) compared with Indomethacin that have binding energy (-10.09 kcal/mol) and it’s have high selectivity towered COX-2 enzyme in the other hand In the present study, the predicted Pharmacokinetic (PK) values of Inhibitor (1) and Indomethacin (NSAID) deduce that Inhibitor (1) satisfies all PK parameters and has qualified as best lead candidate as an Anti-inflammatory agent compared to Indomethacin

Synthesis and Biological Activity of New Derivatives of Thiazolidine and Oxazepine-Linked to Pyridine Moieties

This research includes reaction and condensation between substituted 4-aminopyridine and 4-(N, N-dimethyl amino benzaldehyde) to produce Schiff base derivative (3), the compound (3) was selected to react with a different compound such as Thioglycolic acid, Phthalic anhydride, and maleic anhydride, to produced new ring of Thiazolidine derivatives and oxazepine derivatives structures (4,5,6,7,8,9,10,11,12), respectively. The final compound was characterized the structure by Fourier transform-infrared spectroscopy, H-Nuclear magnetic resonance (H-NMR) in addition to the Carbon, Hydrogen, Nitrogen (CHN) analyzer. Biological activity has been considered for the final structures and achievements of multi drugs.

Facile synthesis and antimicrobial activity of bis(fused 4H‐pyrans) incorporating piperazine as novel hybrid molecules: Michael's addition approach

AbstractA new series of bis(4H‐chromene), bis (pyrano[3,2‐c]chromene), and bis (pyrano[2,3‐c]pyrazole) each linked to the piperazine core via ether linkages was synthesized. The target compounds are probably formed through a three‐component reaction involving two equivalents of each malononitrile and the corresponding active methylene compounds, such as dimedone, 4‐hydroxycoumarine, or 5‐methyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one. Several spectral methods and elemental analyses were used to deduce the chemical structures of the novel compounds. Furthermore, all synthesized compounds were tested for antimicrobial activity, which revealed promising inhibitory results against a variety of multidrug‐resistant microbial strains. These findings were compared to those obtained in the in silico molecular docking study. The docking results improved the activity of new derivatives as potentially effective antimicrobial agents.

Experimental study of the pharmacological activity of new azaheterocycles derivatives: A literature review

Diseases associated with the pathology of the cardiovascular system are one of the key causes of death all over the world. In particular, arrhythmia may entail the most severe complications, including unexpected death. With high-tech advances, antiarrhythmic drugs remain an integral part of both therapy and prevention. However, the existing arsenal of drugs often does not provide the necessary clinical effect, and therapy is associated with a high risk of severe adverse events. Another significant problem today is the administration of low-toxic drugs that provide effective anesthesia with a sufficient depth and duration of action. Currently, there is also the problem of the limited effectiveness of many drugs with antitumor, antimicrobial, antiviral, antifungal, anti-inflammatory activity and action on the central nervous system. One of the solutions to address the existing problems in these areas is the search and study of compounds that may serve as a basis for the development of new drugs. Given the membrane-stabilizing action by influencing ion channels, new derivatives of azaheterocycles- compounds of piperidine and piperazine are of particular interest in these areas of medicine. According to domestic studies, new piperidine derivatives during screening and in-depth studies showed pronounced local anesthetic activity during infiltration and conduction anesthesia. The results of a number of studies confirm the presence of antiarrhythmic activity in piperidine derivatives. Experimental data on the synthesis and study of the pharmacological activity of new derivatives of piperidine and piperazine in world practice prove their promise for the creation of drugs in various fields of medicine in the future.

ASSESSMENT OF ANXIOLYTIC POTENTIAL OF NEW С2,С3- QUINOXALINE DERIVATIVES

The anxiolytic effect of a new series of C2,C3-quinoxaline derivatives was studied using the "Anxious-phobic state" and "Light/Dark chamber" techniques in comparison with diazepam. It was noted that the presence of a phenyl substituent at the C3 position, which did not contain elements with a distinct electronegativity, as well as 2-methyl-(4,5-dimethoxyphenyl)-N-methylethane-1-amine at the C2 position, had a positive effect on the manifestation of the antianxiety activity of new derivatives of C2,C3-quinoxaline. For the most active compound under the code ZDM-4, the conflict method "Vogel Conflict test" was additionally carried out to confirm the anxiolytic effect of the substance. The tranquiLizing potential of the ZDM-4 compound is of interest for further study.

INVESTIGATION OF THE FUNGICIDAL ACTIVITY OF NEW DERIVATIVES OF 7-R-1,5-DINITRO-3,7- DIAZABICYCLO[3.3.1]NONAN-2-ONE

ackground. The problem of finding new effective fungicides for agriculture remains an urgent task of modern agrochemistry. The problem is exacerbated by the fact that, on the one hand, over the years, there has been an ever wider spread of fungi-phytopathogens, due to the intensification of agricultural production, and, on the other hand, there is an increase in the resistance of pathogens of fungal diseases to the available fungicides. This study is devoted to the study of the fungicidal activity of new derivatives of 3,7-diazabicyclo[3.3.1]nonane – 7-R-1,5-dinitro-3,7-diazabicyclo[3.3.1]nonan-2-ones. It is known that 3,7-diazabicyclononane derivatives have versatile biological activity, including showing antibacterial and fungicidal action. Previously obtained 7-R-1,5-dinitro-3,7-diazabicyclo[3.3.1]nonan-2-ones were studied for the manifestation of fungicidal activity in vitro in relation to phytopathogenic fungi of various taxonomic classes, which are the main cause diseases of agricultural crops.
 Purpose. To investigate the fungicidal activity of new derivatives of 7-R-1,5-dinitro-3,7-diazabicyclo[3.3.1]nonan-2-ones on various phytopathogenic fungi, causative agents of the main fungal diseases of agricultural plants.
 Materials and methods. The synthesized compounds were tested in vitro for fungicidal activity against seven fungi-phytopathogens of various taxonomic classes: V. inaequalis is the causative agent of apple scab, F. moniliforme is the main cause of fusarium diseases of cereal crops, R. solani is the causative agent of rhizoctonia, F. oxysporum, B sorokiniana - cause root rot, S. sclerotiorum is the causative agent of white rot, and P. ostreatus is the causative agent of tree stem rot. To determine the radial growth of mycelium, the fungal cultures were inoculated in agar nutrient medium with the addition of the test substance. The effective concentration of the drug in the sample was 30 mg/l. The suppression of fungal mycelium growth was calculated as a percentage using the Abbott`s formula. Measurements were carried out on the 3rd day. Commercial fungicides were selected as a comparison standard from the list of drugs presented in the State Catalog of Pesticides and Agrochemicals permitted for use on the territory of the Russian Federation.
 Results. Most of the studied substances exhibit fungicidal activity. Some compounds have a pronounced fungicidal activity comparable to Russian commercial fungicides.
 Conclusion. Thus, when studying the fungicidal activity of new 3,7-diazabicyclo[3.3.1]nonanes (bispidines) – 7-R-1,5-dinitro-3,7-diazabicyclo[3.3.1]nonan-2-ones on various fungi-phytopathogens, it was shown that some of the obtained compounds have pronounced fungicidal activity and are promising for further testing.

New Coumarin-Pyrazole hybrids: Synthesis, Docking studies and Biological evaluation as potential cholinesterase inhibitors

A new set of hybrid derivatives bearing pyrazole and coumarin scaffold 3a-f was synthesized and confirmed by different spectroscopic techniques (1H NMR, 13C NMR, FT-IR) and mass spectrometry. This study aimed to evaluate the inhibitory activity of new derivatives against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using Galanthamine as standard drugs. In vitro studies showed that compounds 3e and 3f were the most effective showing high potential AChE inhibitory activities with respective IC50 values of 4.41±0.53 and 5.04±0.96 µg/ml. Compounds 3a and 3b were found to be the best butyrylcholinesterase inhibitor with an IC50 value comparable to that of the standard drugs. All the newly synthesized derivatives 3a–f are evaluated for their antioxidant activity and showed good activity. Molecular docking study was also carried to get insights into binding interactions of synthesized compounds to act as AChE and BChE inhibitors. The docking study of compound 3e with AChE enzyme showed that PAS are occupied by the ligand. In silico predictions of toxicity analysis indicated that these compounds should have good oral bioavailability.

Synthesis and Antiviral Activity of New Derivatives of Rupestonic Acid

Synthesis and Antiviral Activity of New Derivatives of Rupestonic Acid