جستجوی مقالات مرتبط با کلیدواژه « synthesis » در نشریات گروه « پزشکی »

 According to the cholinergic hypothesis for Alzheimer’s disease, potentiation of cholinergic neurotransmission is one of the best strategies for combating dementia.

 A new series of benzamide derivatives bearing 1,3,4-thiadiazole nucleus were synthesized and subsequently, their anticholinesterase activity was evaluated. Molecular docking was carried out to explore the likely binding mode and interactions.

 Fortunately, some of the tested compounds exhibited more activity than donepezil as a reference drug (IC50 = 0.6 ± 0.05 µM). Some of the evaluated derivatives displayed potency in the nanomolar range. Compound 7e with fluorine atom on the meta position of the phenyl ring was the most active compound in this series (IC50 = 1.82 ± 0.6 nM).

 The 1,3,4-thiadiazole derivatives that were synthesized and tested in the current manuscript demonstrated remarkable anticholinesterase activity. Therefore, these compounds could be suggested as potential anti-Alzheimer agents.

Synthesis studies are used for the retrieval, review, synthesis, analysis, and integration of the findings of original studies. The purpose of this review was to shed more light on how meta-ethnography works as a method of inductive and interpretative knowledge synthesis, and on its application and implementation in medical sciences.

This was a narrative review study and the statistical population included all scholarly publications on the synthesis of qualitative studies and meta-ethnography published from 1998 to 2022. The search in international and domestic databases led to the extraction of 118 books and articles. After reviewing the titles, abstracts, and full texts of these publications, we included 2 books and 8 articles in the review.

Meta-ethnography is used for synthesizing the knowledge obtained from qualitative studies to re-conceptualize their findings. There are seven phases in the process of meta-ethnography: Getting started; Deciding on what is of initial interest; Reading the studies; Determining how the studies are related; Translating the studies to each other; Synthesizing the translations; and expressing the synthesis. The number of studies required to perform meta-ethnography has been recently suggested to be 40. Strategies for updating meta-ethnography include repeating the previous strategy and reformulating the strategy according to a new objective, a revised review question, or new inclusion criteria.

Noblit and Hare introduced meta-ethnography in 1988 as a qualitative research method for the synthesis of educational ethnographies. Today, it is widely used in healthcare research.

 Drugs containing the 4-anilinoquinazolines scaffold play a critical role in cancer treatment by inhibiting protein kinases, especially tyrosine kinases. In this study, a novel series of 4-anilinoquinazoline derivatives were synthesized and evaluated as cytotoxic agents.

 All final compounds were synthesized using two methods, including a conventional approach using potassium iodide and dimethylformamide as well as a green method using a deep eutectic solvent (DES) comprising choline chloride: urea. The cytotoxicity was tested on the A431, HUVEC, and HU02 cell lines. To evaluate the binding pattern of the compounds with EGFR and VEGFR-2, a molecular docking investigation was performed. Finally, the wound healing assay was carried out to assess the potency of compounds in inhibiting cell migration.

 The final reaction time was approximately 15-20 min with yields of 60-72% using DES, while the conventional method took 3 to 4 h to complete, with yields between 30% and 42%. Compounds 8k and 8l showed better cytotoxicity against both cell lines compared to vandetanib (IC50=0.11 µM and 0.26 µM on A431 and IC50=5.01 µM and 5.24 µM on HUVEC, respectively). Molecular docking studies revealed that compound 8k, which contained 3-methylaniline at the 4-position of the quinazoline core, showed efficient binding affinity to both EGFR and VEGFR-2. An essential hydrogen bond was formed between quinazoline N1 of 8k and the Met796 residue of EGFR with a docking score of -8.76 kcal/mol. The imidazole N3 of 8k interacted with the Cyc919 residue of VEGFR-2, forming a hydrogen bond with a docking score of -9.03 kcal/mol. Moreover, compound 8k exhibited the best inhibitory activity on cell migration and wound healing.

 DES significantly improved the time and yield of the final reactions. Compound 8k, which showed the best cytotoxicity and inhibitory activity on cell migration, could be a suitable candidate for further structural optimization.

Thalassemia is a genetic disease that significantly affects human health. The common treatment of thalassemia is the regular injection of red blood cell, which is associated with the accumulation of iron in different tissues of the body, and makes chelation therapy necessary. Deferiprone and deferoxamine are broadly used as iron chelating agents in the vast majority of thalassemia cases. In this study, an efficient method for the synthesis of deferiprone was used by reacting maltol with methylamine in a mixture of water and ethanol as solvent. The structure of deferiprone was assigned using different spectroscopic techniques such as IR, 1H-NMR, and 13C-NMR. The advantages of this pathway are simple, practical, one-pot cascade, mild condition and high yield. The statistics of the Ministry of Health of Iran show the growing trend of deferiprone drug consumption in the country. Therefore, the domestic preparation of this drug can help the pharmaceutical industry in order to reduce costs and make it available for target patients.Keywords: Synthesis, Deferiprone, Maltol, Methylamine, Iron chelating agent.

Context: 

The recent growth of research and the vast amount of knowledge available highlight the necessity for synthesizing existing research in a reliable and high-quality manner. The substantial body of qualitative meta-synthesis studies on chronic diseases indicates the need for a deeper understanding of this methodology. Therefore, the purpose of this paper was to explain the process of meta-synthesis in qualitative research.

 This was a narrative review with predefined inclusion and exclusion criteria, followed by a web search using relevant keywords. Initially, 980 relevant articles were selected. Subsequently, the titles, abstracts, and full texts were assessed for eligibility using the Critical Appraisal Skills Program checklist. Finally, 21 articles were included in this study.

 Various approaches have been adopted to address the meta-synthesis of qualitative studies. Common types of qualitative meta-synthesis include meta-narrative, critical interpretive synthesis, meta-study, meta-ethnography, grounded formal theory, thematic synthesis, textual narrative synthesis, framework synthesis, and ecological triangulation. However, concerning chronic diseases, the most commonly used methods were ethnography and Sandelowski and Barroso’s method.

 Meta-synthesis is a method for integrating the results of studies, re-understanding the findings, and ultimately interpreting them to generate new insights beyond what is obtained from individual studies. Given the extensive body of qualitative research on chronic diseases, it is recommended to conduct this type of research to develop new knowledge based on the findings of previous studies.

Alzheimer’s disease (AD), the main form of dementia, is a multifactorial neurodegenerative disease, and several hypotheses have been proposed for its pathogenesis. Among them, cholinergic hypofunction is the main reason and plays a significant role in cognitive impairment. According to this theory, ChE inhibitors improve the performance of the cholinergic system and increase memory function. Thus, this study investigated a novel series of 2-amino-pyrano[3,2-c]quinoline-3-carbonitrile derivatives bearing benzyloxy phenyl moiety as ChE enzyme inhibitors.

The synthesized compounds 6a-o are divided into three series based on benzyloxy phenyl moiety. The structure of all compounds was identified by the NMR (1H and 13C) and IR spectra. Then, their inhibitory activities against ChE enzymes were evaluated by Ellman’s spectrophotometrical method. The kinetic and molecular docking studies were performed for compound 6l as the most potent butyrylcholinesterase (BChE) inhibitor.

The 2-amino-4-(4-((4-fluorobenzyl)oxy)-3-methoxyphenyl)-5-oxo-5,6-dihydro-4H-pyrano[3,2-c] quinoline-3-carbonitrile (6l) demonstrated the best anti-BChE activity with a half maximal inhibitory concentration value of 1.00 ± 0.07. The kinetic and molecular docking studies confirmed that 6l is a mixed inhibitor and binds to both the anionic catalytic site and peripheral anionic site (PAS) of BChE. In silico study approved that the methoxy group on the middle phenyl ring has a significant role in interacting with the PAS of the enzyme.

These findings indicated that 2-amino-pyrano[3,2-c]quinoline-3-carbonitrile derivatives bearing benzyloxy phenyl moiety have therapeutic potential as BChE inhibitors in the last stages of AD.

A new series of derivatives of N, 2-diphenylquinazolin-4-amine (3a-g) was synthesized through nucleophilic substitution. The structures of compounds were characterized by FTIR, 1H-NMR, and 13C-NMR spectroscopy. All synthesized compounds were evaluated for their antimicrobial activities against Gram-positive (Staphylococcus aureus, Bacillus subtilis, Lactobacillus rhamnosus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and also for antifungal activities, against Candida albicans, using broth microdilution method to determine their minimum inhibitory concentrations (MIC). Most of the compounds have shown moderate to good antibacterial activities, significantly compound 3g at 0.0625 mg/mL concentration had the highest activity against P. aeruginosa. Also, the MIC of compound 3f was 0.0078 mg/mL against S. aureus. Furthermore, the tested compounds exhibited remarkable antifungal activities against C. albicans, significantly compounds 3c and 3g showed the least MIC (equal to 0.0625 mg/mL). Also, a docking study into DNA gyrase has been made for these compounds. The synthesized compounds showed dock score values between -3.05 and -6.13kcal/mol. The highest dock score among them was -6.13 kcal/mol, found for compound 3c.

This review describes the Food and Drug Administration (FDA)-approved antiparasitic drugs for sheep and goats in the USA updated to 2021. The emerging drug resistance is posing a significant burden for the treatment of parasitic infections in these small ruminants and the need for novel antiparasitic drugs is urgent. Sheep and goats are producing every year important resources such as milk and wool, among others. This work incorporates the OneHealth approach which focuses not only on human health, but also on animal health and the environment in an interdependent modus operandi. The dynamic equilibrium among these three sectors plays a fundamental role in general healthcare. Drug discovery (e.g., a novel benzimidazole recently identified) and drug delivery (incorporation of the antiparasitic agent into the proper carrier to increase effectiveness) have provided some promising results in recent time. This should go hand-in-hand with the scientific awareness. Education is key in spreading the word about the responsible use of antiparasitic drugs. The synthesis of the currently approved drugs will be provided including synthetic procedures which date from 1961 to 2021. More synthetic pathways, when available, will be described. Their mechanism of action and ecotoxicological data will be presented as well.

Since several Helicobacter pylori strains have become resistant to metronidazole, new nitroimidazole derivatives based on metronidazole were designed and synthesized with different substituents on imidazole nitrogen. The activity of the synthesized compounds was evaluated against 20 clinically isolated metronidazole-resistant H. pylori strains. Some synthesized compounds were effective against those metronidazole-resistant H. pylori strains. Three compounds exhibited the most potent inhibitory activities (MIC50 = 8 µg/mL and MIC90 = 16 µg/mL).

The incidence of antibiotic resistance rapidly emerges over the globe. In the present study, the synthesis of thiourea derivatives as antibacterial agents and their biological evaluation are reported.

Experimental approach: 

Preliminary studies were done by molecular docking of four analogs of 1-allyl-3- benzoylthiourea, clorobiocin, and ciprofloxacin on the DNA gyrase subunit B receptor (PDB: 1KZN). The nucleophilic substitution reaction of benzoyl chloride analogs to the allylthiourea yielded four 1-allyl-3- benzoylthiourea analogs (Cpd 1-4). The reactions were done by a modified Schotten Baumann method. The in vitro antimicrobial activities were determined using the agar dilution method against methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhi, Escherichia coli, and Pseudomonas aeruginosa.

The in-silico study showed that Cpd 1-4 possesses a good interaction on the DNA gyrase subunit B receptor compared to the ciprofloxacin. Cpd 3 had the best binding affinity with a rerank score of - 91.2304. Although the candidate compounds showed unsatisfactory antibacterial activity, they indicated an increasing trend of growth inhibition along with the increment of concentration. Cpd 1 and 4 exhibited in vitro antibacterial activities against MRSA with a minimum inhibitory concentration value of 1000 μg/mL, better compared to the other compounds.

Conclusion and implication: 

Despite lacking antibacterial activity, all the synthesized compounds showed an increased trend of growth inhibition along with the increment of concentration. Therefore, additional development should be implemented to the compounds of interest in which optimization of lipophilicity and steric properties are suggested.

As one of the most well-known metal nanoparticles, gold nanoparticles (AuNPs) have attracted much attention for the biological applications. This great interest in AuNPs can be attributed to their outstanding physical and chemical properties, such as special optical and electrochemical characteristics, high X-ray attenuation ability, strong X-ray absorption, photothermal effect, stability and biocompatibility. In addition, due to the ease of synthesis and modification of the surface of AuNPs, it is possible to control their shape, size and surface characteristics. All these features suggest that AuNPs can be used for biosensing strategies, drug delivery, photothermal therapy, nanobrachytherapy, enhanced radiotherapy and CT imaging. In addition, they can be used as antibacterial and antifungal agents. This minireview focuses on the key principles, research achievements and new opportunities in the synthesis of AuNPs as well as their biological applications. In fact, the growing progress in the use of AuNPs for the diagnostic and therapeutic applications is described in this survey. Overall, a better understanding of the key aspects of the synthesis methodologies will lead to the development of new protocols that can provide ideas for more cost-effective and reliable approaches to the production of AuNPs.

Echinochloa esculenta is the Indian Barnyard millet which is a grass type of species. This study focused on the evaluation of the antibacterial activity of Echinochloa esculenta-mediated zinc oxide nanoparticles (ZnONPs) against urinary tract infection (UTI) microbes, such as Escherichia coli ( E. coli), Enterobacter aerogenes, Pseudomonas aeruginosa, Staphylococcus aureus, and Proteus vulgaris.

The millet Echinochloa esculenta-mediated ZnONPs are synthesized using a green method. Synthesized ZnONPs are characterized by ultraviolet (UV), Fourier transform-infrared resonance spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX) to determine the functional groups, crystalline size, shape, and elemental composition of the synthesized NPs.

The UV and FTIR results of Echinochloa esculenta-mediated ZnONPs preliminarily confirmed the formation of ZnONPs. The XRD and SEM results also confirmed that the synthesized ZnONPs are well-crystalline in nature, and the average size was observed to be 23.38 nm with a spherical shape. Echinochloa esculenta-mediated ZnONPs contained 73.33% of zinc and 26.77% of oxygen, which was examined by EDX. Synthesized ZnONPs were tested against the five UTI pathogens, and they exhibited a greater zone of inhibitions than zinc acetate and plant extract. Especially against S. aureus, Echinochloa esculenta-mediated ZnONPs performed well with an inhibitory effect.

Therefore, this study had the potential value of developing new eco-friendly, low-cost, and less toxic nanomaterials that can be used as a bio-control for diseases.

The Human Immunodeficiency Virus (HIV) infection is a global health challenge that creates an urgent need todevelop new therapeutic agents. In this work, a new group of quinazolinone derivatives were designed andsynthesized and evaluated their anti-HIV activity. The antiviral assay revealed that some analogues inhibited HIVreplication in the cell culture. A docking study using the later crystallographic data available for PFV integraseincluding its complexes with Mg2+ and dolutegravir, showed that the designed compounds bind into the active siteof integrase enzyme such that both carbonyl groups chelate Mg2+ ions. Interestingly, all of the synthesizedcompounds were found to present no significant cytotoxicity at a concentration of 100 μM. According to the antiHIV evaluation results, the compound 10f was found as the most active with the inhibition rate of 38%. Therefore,these compounds can provide a very good basis for the development of new anti-HIV agents.

Quinazolinone and quinazoline have been shown different pharmacological activities, namely anticancer, anti?inflammatory, anti?hyperlipidemia, analgesic, antihypertensive, and antibacterial. On the other hand, molecular hybridization is a structural modification technique in the design of new ligands which consist of two or more pharmacologically active molecules in one structure. Therefore, due to the importance of the biological activities of quinazolinones for the development of new therapeutic agents, this review emphasizes current findings on various quinazolinone?based hybrids in medicinal chemistry. Moreover, it highlights the biological activities and structure?activity relationship of these hybrids.

HIV, the virus that causes AIDS (acquired immunodeficiency syndrome), is one of the world’s most severe health and development challenges. In this study, a novel series of 2-(diphenyl methylidene) malonic acid derivatives were designed as triple inhibitors of HIV reverse transcriptase, integrase, and protease. Docking models revealed that the target compounds have appropriate affinities to the active sites of the three HIV key enzymes. The synthesized malonic acid analogs were evaluated for their activities against the HIV virus (NL4-3) in HeLa cells cultures. Among them, compound 3 was the most potent anti-HIV agent with 55.20% inhibition at 10 µM and an EC50 of 8.4 µM. Interestingly, all the synthesized compounds do not show significant cytotoxicity at a concentration of 10 µM. As a result, these compounds may serve as worthy hits for the development of novel anti-HIV-agents.

The development of a highly safe and potent scaffold is a significant challenge in anti-HIV drug discovery.

This study aimed at developing a novel series of anti-HIV agents based on HIV integrase inhibitor pharmacophores.

A novel series of 8-methyl-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives featuring various substituted benzoyl and N-phenyl carboxamide and carbothioamide moieties were designed and synthesized.

According to the biological evaluation, all the developed compounds were effective against HIV at concentrations lower than 150 µM, associated with no significant cytotoxicity (CC50 > 500 µM).

Compound 8b, possessing a 4-fluorobenzoyl group, was the most potent compound, with an EC50 of 75 µM. Docking studies revealed that the binding modes of designed compounds are similar to the known HIV integrase inhibitors.