Synthesized Pyrimidine Derivatives Research Articles

Pyrimidine-based sulfonamides and acetamides as potent antimicrobial Agents: Synthesis, Computational Studies, and biological assessment

A series of novel sulfonamide and acetamide derivatives of pyrimidine were synthesized and their antimicrobial activities were assessed. Based on the Microbroth dilution method, the minimum inhibitory concentration (MIC) of the synthesized compounds demonstrated moderate to good levels of antifungal and antibacterial activity. Structure-activity relationship analysis suggested that the presence of electron-withdrawing groups, such as halogens, nitrile, and nitro groups, on the pyrimidine ring contributed to the enhanced antimicrobial potency, while electron-donating substituents led to a decrease in activity. Computational studies, including density functional theory (DFT), frontier molecular orbitals (FMO), and molecular electrostatic potential (MEP) analysis, provided insights into the electronic properties and charge distribution of the compounds. Drug-likeness evaluation using ADME/Tox analysis indicated that the synthesized compounds possess favorable physicochemical properties and could be potential drug candidates. Molecular docking against the Mycobacterium TB protein tyrosine phosphatase B (MtbPtpB) revealed that the synthesized compounds exhibited strong binding affinities (−46 kcal/mol to − 61 kcal/mol) and formed stable protein–ligand complexes through hydrogen bonding and π-π stacking interactions with key residues in the active site. The observed interactions from the docking simulations were consistent with the predicted interaction sites identified in the FMO and MEP analyses. These findings suggest that the synthesized pyrimidine derivatives could serve as promising antimicrobial agents and warrant further investigation for drug development.

Synthesis and biological studies of pyrimidine derivatives targeting metabolic enzymes.

Novel synthesized pyrimidine derivatives were investigated against carbonic anhydrase isoenzymes I and II (hCA Iand II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-glycosidase, and aldose reductase (AR) enzymes associated with some common diseases such as epilepsy, glaucoma, Alzheimer's disease, diabetes, and neuropathy. When the results were examined, novel synthesized pyrimidine derivatives were found to have effective inhibition abilities toward the metabolic enzymes. IC50 values and Ki values were calculated for each pyrimidine derivative and compared to positive controls. The synthesized novel pyrimidine derivatives exhibited Ki values in the range of 39.16 ± 7.70-144.62 ± 26.98 nM against hCA I, 18.21 ± 3.66-136.35 ± 21.48 nM towardhCA II, which is associated with different pathological and physiological processes, 33.15 ± 4.85-52.98 ± 19.86 nM on AChE, and 31.96 ± 8.24-69.57 ± 21.27 nM on BChE. Also, Ki values were determined in the range of 17.37 ± 1.11-253.88 ± 39.91 nM against α-glycosidase and 648.82 ± 53.74-1902.58 ± 98.90 nM towardAR enzymes. Within the scope of the study, the inhibition types of the novel synthesized pyrimidine derivatives were evaluated.

Design, Docking, Characterisation, and Synthesis of Pyrimidine Derivatives for Antidepressant Activity.

According to the report, in 2022, the prevalence rate of depression in India was 4.50%, and the cases stood at 56,675,969. The development of antidepressant agents has reduced the number of depressant and suicidal cases. Many researchers have found that pyrimidine possesses antidepressant activity. With this background, we thought of synthesizing pyrimidine derivatives. The objective of this study is to carry out molecular docking, synthesis, characterization, and evaluation of 2-((4,6-diphenylpyrimidin-2-yl)oxy)-N-phenylacetamide derivatives (17-26) as in vivo antidepressant agent. The designed compounds were checked for their activity using Molegro virtual docker (MVD) and were further synthesized. Benzaldehyde reacted with acetophenone to give compound (3), which gave compound (4) upon reaction with urea. In another reaction, substituted anilines (5) were reacted with chloroacetyl chloride (6) to yield compounds (7-16), which upon further reaction with compound (4) yielded the final derivatives (17-26). The synthesized compounds were characterized by spectral analysis and checked for their antidepressant activity. The MolDock scores of the derivatives ranged from -147.097 to -182.095, whereas of active ligand IXX_801 was -115.566. All the synthesized pyrimidine derivatives showed better affinity towards the Cryo-EM structure of the wild-type human serotonin transporter complexed with vilazodone, imipramine, and 15B8 Fab protein (PDB ID: 7LWD) as compared to standard drug clomipramine (-101.064). All the synthesized derivatives were screened for antidepressant activity at a 100mg/kg dose level compared to the standard clomipramine HCl at a dose level of 20mg/kg. Among all the synthesized derivatives, compound 24 showed the most potent antidepressant activity, and Compound 20 showed moderate antidepressant activity, which reduced the duration of immobility times to 35.42% and 31.97% at 100mg/kg dose level when compared to the control, respectively. Compound 24 showed the highest MolDock score as well as found to be the most potent antidepressant agent.

Synthesis and Study of Steering of Azido-tetrazole Behavior in Tetrazolo[1,5-c]pyrimidin-5-amine-Based Energetic Materials.

Tetrazoles and their derivatives are essential for compound synthesis due to their versatility, effectiveness, stability in air, and cost-efficiency. This has stimulated interest in developing techniques for their production. In this work, four compounds, tetrazolo[1,5-c]pyrimidin-5-amine (1), N-(4-azidopyrimidin-2-yl)nitramide (2), tetrazolo[1,5-c]pyrimidin-5(6H)-one (3), and tetrazolo[1,5-a]pyrimidin-5-amine (4), were obtained from commercially available reagents and straightforward synthetic methodologies. These new compounds were characterized by infrared (IR), 13C, and 1H NMR spectroscopy, differential scanning calorimetry (DSC), and single-crystal X-ray diffraction. The solvent, temperature, and electron-donating group (EDG) factors that were responsible for the steering of azido-tetrazole equilibrium in all compounds were also studied. In addition, the detonation performance of the target compounds was calculated by using heats of formation (HOFs) and crystal densities. Hirshfeld surface analysis was used to examine the intermolecular interactions of the four synthesized compounds. The results show that the excellent properties of 1-4 are triggered by ionic bonds, hydrogen bonds, and π-π stacking interactions, indicating that these compounds have the potential to be used in the development of high-performance energetic materials. Additionally, DFT analysis is in support of experimental results, which proved the effect of different factors that can influence the azido-tetrazole equilibrium in the synthesized pyrimidine derivatives in the solution.

Microbiological screening of compounds with potential anti-lep activity among new synthesis compounds of the pyrimidine series

Aim. To study the effect of new synthesized pyrimidine derivatives on the growth of Mycobacterium lufu (M. lufu) and Mycobacterium tuberculosis (M. tuberculosis) when cultivated on Shkolnikova's medium.Materials and methods. The objects of research were new synthesized derivatives of 6 samples of derivatives of pyrimidine - 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-trions under laboratory codes TAG1, TAG2, TAG3, TAG4, TAG5, TAG6 and 7 samples of 5-(getarylmethylidene)-2,4,6-pyrimidine-2,4,6(1H, 3H, 5H)-trions under the laboratory codes TAG7, TAG8, TAG9, TAG10, TAG11, TAG12, TAG13. M. lufu and M. tuberculosisH37Rv strains were used as test cultures. The antimycobacterial activity of the studied compounds was studied by the method of serial dilutions.Research results. All studied compounds were found to exhibit antimycobacterial activity. The greatest inhibitory effect against M. lufu was noted for TAG1, TAG4, TAG7, TAG12, and TAG13, which was comparable to that of the reference drug dapsone. By the nature of the inhibitory effect on the growth of M. tuberculosis, the compounds under the laboratory codes TAG 1, TAG 4, TAG 7 and TAG13 were comparable to isoniazid, and the effect of the TAG3 compound was even slightly superior to the reference drug.Conclusion. Among the studied new synthesized pyrimidine derivatives, compounds under the laboratory codes TAG1, TAG4, TAG 7 and TAG13 have the most pronounced antimicrobial activity both against M. lufu and M. tuberculosis, which allows us to consider them as the most promising substances for further research on the search for antimycobacterial, including antileprosy drugs.

Microbiological screening of compounds with potential anti-lep activity among new synthesis compounds of the pyrimidine series

Aim: To study the effect of new synthesized pyrimidine derivatives on the growth of Mycobacterium lufu (M. lufu) and Mycobacterium tuberculosis (M. tuberculosis) when cultivated on Shkolnikova’s medium.Materials and methods. The objects of research were new synthesized derivatives of 6 samples of derivatives of pyrimidine - 5-(arylmethylidene)-2,4,6-pyrimidine-2,4,6(1H,3H,5H)-trions under laboratory codes TAG1, TAG2, TAG3, TAG4, TAG5, TAG6 and 7 samples of 5-(getarylmethylidene)-2,4,6-pyrimidine-2,4,6(1H, 3H, 5H)-trions under the laboratory codes TAG7, TAG8, TAG9, TAG10, TAG11, TAG12, TAG13. M. lufu and M. tuberculosisH37Rv strains were used as test cultures. The antimycobacterial activity of the studied compounds was studied by the method of serial dilutions.Research results. All studied compounds were found to exhibit antimycobacterial activity. The greatest inhibitory effect against M. lufu was noted for TAG1, TAG4, TAG7, TAG12, and TAG13, which was comparable to that of the reference drug dapsone. By the nature of the inhibitory effect on the growth of M. tuberculosis, the compounds under the laboratory codes TAG 1, TAG 4, TAG 7 and TAG13 were comparable to isoniazid, and the effect of the TAG3 compound was even slightly superior to the reference drug.Conclusion. Among the studied new synthesized pyrimidine derivatives, compounds under the laboratory codes TAG1, TAG4, TAG 7 and TAG13 have the most pronounced antimicrobial activity both against M. lufu and M. tuberculosis, which allows us to consider them as the most promising substances for further research on the search for antimycobacterial, including antileprosy drugs.

Studies on pyrimidine derivative as green corrosion inhibitor in acidic environment: Electrochemical and computational approach

Present investigation describes the green corrosion inhibition and adsorption behaviour of two synthesized pyrimidine derivatives, namely, 6,6′-(1,4-phenylene)bis(4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) (POTC) and 6,6′-(1,4-phenylene)bis(5-chloro pyrimidine-2,4(1 H,3 H)-dione) (PCPD) on mild steel in 15% HCl environment. The corrosion inhibition capability of the synthesised inhibitors was measured with the help of weight loss & electrochemical techniques. The corrosion inhibition efficiency measured by the weight loss experiment for the POTC and PCPD inhibitor at 200 ppm concentration & 303 K temperature was 96.9% and 93.3%, respectively. Both inhibitors obey Langmuir adsorption isotherm and mixed (physisorption as well as chemisorption) nature of adsorption because the magnitude of free energy of adsorption for both inhibitors lies in the range of − 35.99 to − 37.93 kJmol−1. The results of Tafel polarization notified that both inhibitors suppressed the rate of cathodic and anodic corrosion reactions and designated as mixed type inhibitor. The observations of FESEM, EDX, AFM, and XPS suggested the formation of protective film of inhibitor on mild steel surface. The computational investigations (DFT & MCS) well support the experimental outcomes of both inhibitors.

Assessment of Antimycobacterial Activity of Newly Synthesized Pyrimidine Derivatives Against Mycobacterium tuberculosis

Background. The current trend of growing antibiotic resistance among pathogenic microorganisms remains one of the urgent and significant problems of mankind. The constant spread of resistant strains of microorganisms requires the development of innovative methods and the search for medicinal compounds with a highly effective mechanism of action. One of these multi-resistant pathogens that are difficult to eradicate is the causative agent of tuberculosis — Mycobacterium tuberculosis. The aim is to study the effect of newly synthesized pyrimidine derivatives on the growth of Mycobacterium tuberculosis culture, as well as on the structural changes in cells.Material and methods. In order to assess the effect of a number of pyrimidine derivatives on the growth of Mycobacterium tuberculosis culture, 6 samples of 5-(arylmethylene) hexahydropyrimidine-2,4,6-triones (TAG1 — TAG6), 7 samples of 5-hetarylmethylidene-2,4,6-triones (TAG7 — TAG13), and 2 new samples of 3-(2-Benzyloxy-2-oxoethyl)quinazoline-4(3H)-one and 3-[2-(1-Naphthyl)-2-oxoethyl]quinazoline-4(3H)-one were screened under the laboratory ciphers VMA-13-03 and VMA-13-04 in the course of the study. M.tuberculosis H37RV strain was used as a test culture; it was provided by the bacteriological laboratory of the Regional Infectious Clinical Hospital named after A. M. Nichoga. A 4-week culture of M.tuberculosis, synchronized by cold (+4°C) for 72 hours, was used to prepare a suspension of mycobacteria. The number of mycobacteria in the suspension was determined using the McFarland 0.5 turbidity standard. 0.2 ml of M.tuberculosis working suspension was added to each tube of a series of successive dilutions of the studied substances, including the control. The study was carried out in 4 series of replicates. The minimum bactericidal concentration of the compounds, at which no colony growth was detected, as well as the minimum inhibitory concentration, at which mycobacterium growth was delayed by 50% compared to the control, were determined. Smears were prepared from the sediment for staining using theZiehl-Neelsen method to determine the presence of acid-resistant and non-acid-resistant forms of mycobacteria, as well as to study the effect of pyrimidines and a comparison drug on structural changes in M.tuberculosis cells.Results. In the course of the study, the TAG4, TAG6, and TAG8 compounds were found to have the closest antibacterial activity to the comparison drug isoniazid, according to the indicator of mycobacteria growth retardation. The greatest bactericidal activity against M.tuberculosis was observed in TAG4, TAG7, and VMA–13–04. The remaining compounds have shown minimal inhibitory effect on the growth of M.tuberculosis. Microscopic studies have shown that under the influence of TAG3, TAG4, TAG7, TAG12, VMA-13-03, and VMA-13-04, the main structural components of M.tuberculosis cells undergo fragmentation and morphological changes compared to mycobacterium cells without exposure.Conclusion. As a result, it was found that all the studied compounds possess antimycobacterial activity. Compounds under the laboratory ciphers TAG1, TAG4, TAG7, and TAG13 were comparable to isoniazid by the nature of the inhibitory effect on the growth of M.tuberculosis, and the TAG3 compound even slightly exceeded the effect of the comparison drug. Compounds under the laboratory codes VMA-13-03, and VMA-13-04 had the least pronounced anti-tuberculosis effect. Compounds under the laboratory codes TAG5, TAG6, TAG11, and TAG12 showed the least antimycobacterial activity.

Microwave Irradiated Eco-friendly Synthesis of Pyrimidine Derivatives as Potential Antitubercular Agents

The microwave irradiation method is applied for the efficient synthesis of pyrimidine derivatives. The synthetic protocol involves Knoevenagel condensation followed by Michael addition reaction and cyclization of equimolar quantities of aromatic aldehydes, ethyl cyanoacetate and guanidine in the presence of ethanolic NaOH solution to produce corresponding pyrimidine derivatives. The reaction mixture was allowed to reflux under microwave radiation at power level-2 for 7-12 min. The microwave heating technique offers a cleaner reaction with a shorter reaction time and improved product yield as compared to conventional synthesis. The newly synthesized compounds were characterized by their FT-IR, 1H NMR and LC-MS spectral data. All the synthesized pyrimidine derivatives were evaluated in vitro for their antitubercular activity in vitro by using the luciferase reporter phage (LRP) assay method. The antimycobacterial activity was determined in terms of the percent reduction in the relative light unit (RLU). The test compounds exhibited promising antitubercular activity against Mycobacterium tuberculosis H37Rv and clinical isolates, S, H, R and E resistant M. tuberculosis in comparison with the standard drug (isoniazid).

Microwave‐assisted diversified synthesis of pyrimidines: An overview

AbstractPyrimidines and their hybrid molecules have continued to be a favorable area for organic chemists owing to their richness in natural and synthetic compounds with multifarious involvement in pharmaceuticals and polymers and act as ligands. Different novel and greener synthetic protocols were developed in the last decades, but microwave‐assisted synthetic protocols played a significant role in constructing pyrimidine and its derivatives. In this article, we summarized the microwave‐supported strategy for the construction of pyrimidine fused or linked/tethered with other heterocycles, polysubstituted pyrimidines, solid‐supported synthesis of pyrimidines, and ionic liquid‐catalyzed strategies for the synthesis of pyrimidine and its derivatives reported in the last decade. Solid‐supported protocols using resins and ionic liquid‐catalyzed strategies afforded the corresponding products with excellent yield by dual activation. In most of the reports, the microwave‐irradiated approach was compared with conventional/traditional heating and found better in terms of reaction time, yield, atom economy, adherence with green chemistry principles, and reduction in purification wastage. Various authors evaluated the in vitro potential of synthesized pyrimidine derivatives for antimicrobial and antimalarial potential, and found moderate to excellent biological activity.

A Facile Synthesis and Biological Screening of Pyrimidine Derivatives under Ultrasonic Irradiations by ZnCr2O4 Nano-Particles Catalyst

Using a recyclable catalyst, facile synthesis of pyrimidine derivatives (4a-e) is attributed through the one-pot multi-component reaction of 2-amino benzimidazole (1) substituted aromatic aldehydes (2a-e) with malononitrile (3) under ultrasonic irradiations. Synthesized derivatives might help society in getting more active pharmaceutical constituents. In this present work, series of substituted pyrimidine (4a-e) were synthesized and confirmed with different spectra characterization methods. The ZnCr2O4 nano-particles play a vital role in eco-friendly, highly efficient, recyclable heterogeneous nanocatalyst. Furthermore, synthesized pyrimidine derivatives showed significant biological activities. Advantages of this handy route are less reaction time, simple isolation, and highly yielded products.

Synthesis, Characterization and Evaluation of some newer Pyrimidine derivatives as Anti-inflammatory Agents

Pyrimidine is an important baseone of the base formed by hydrolysis of nucleosides. It is an interesting molecule in the medicinal chemistry because of its diversified biological activities. Alloxan which is an oxidation product of Uric acid is also a pyrimidine derivative of interest to a medicinal chemist. Several pyrimidines are reported as antimicrobial, analegesic, anti-inflammatory, antibacterial, and antiparasitic agents. Pyrimidine scaffold is considered as an interesting one due to its various pharmacological properties. In this scheme, an attempt is made to carry out synthesis of some new pyrimidine derivatives. The Starting material Chalcone is synthesized by condensation of various aromatic aldehyde and aromatic ketone. Chalcone is then treated with thiourea and KOH in presence of ethanol to yield pyrimidine derivatives. Then those pyrimidine derivatives were subjected to alkylation and acetylation. The synthesized compounds were characterized and confirmed by IR and 1HNMR spectroscopy and then evaluated for their anti-inflammatory activity. The anti-inflammatory activity of newly synthesized pyrimidine derivatives were carried out by the carrageenan induced rat hind paw edema method by taking Diclofenac sodium as standard.

Synthesis and antitumor activity of some nitrogen heterocycles bearing pyrimidine moiety

AbstractSynthesis of novel pyrimidine derivatives 4‐16 was accomplished by heterocyclization of polarized system, for example, Chalcone. Claisen‐Schmidt condensation of 2‐acetyl naphthalene with 4‐(N, N‐dimethylaminobenzaldehyde) afforded chalcone 3, which was utilized for synthesis various pyrimidine derivatives by treatment with urea, thiourea, and guandine hydrochloride in ethanolic sodium hydroxide solution. The reactivity of the synthesized pyrimidine derivatives towards different nucleophilic and electrophilic reagent were examined. The constructions of the newly synthesized pyrimidine derivatives were elucidated from their spectral and elemental analysis. All the synthesized compounds were tested in vitro for their anticancer activities against HePG‐2 and MCF‐7 cell lines. Some of them posses a wide range of pharmacological activity. Finally, a molecular docking study was conducted to reveal the probable interaction with the dihydrofolate reductase (DHFR) active site.

Synthesis and pharmacological profile of some new 2-substituted-2, 3-dihydro-1H-perimidine

Background and objective: The development of new antimicrobial drugs is still demanded as there is increasing resistance of microorganisms to currently available antimicrobial drugs and searches for safer nonsteroidal anti-inflammatory agents with greater cyclooxygenase COX II selectivity is challenging. The new series of 2-substituted-2,3-dihydro-1H-perimidine (4a-j) that are close analogs to Naproxen 5, might inhibit COX II enzyme in a similar manner to naproxen 5. This study aimed to synthesize some new heterocyclic compounds for enhancing biological activity. Methods: 1,8-Diaminonaphthalene 2 was condensed with a variety of aldehydes and ketones 3 to afford a new series of 2-substituted-2,3-dihydro-1H-perimidines4a-j using a suitable synthetic strategy. All the synthesized 2,3-dihydro-1H-perimidine compounds 4a-jwere screened for their invitro antimicrobial activities against two identifiable strains using the agar diffusion method. At the same time, the synthesized pyrimidine derivatives 4a-were evaluated for their COX inhibition activity. Supplementary to these, the constitutions of the newly synthesized 2,3-dihydro-1H-perimidines 4a-j had been confirmed on the basis of their IR, 1H- and 13C-NMR spectral data. Results: The synthesized 2-substituted-2,3-dihydro-1H-perimidine compounds 4a-j exhibited promising antibacterial activity against Escherichia coli microorganism, while none of the synthesized derivatives 4a-jshowed likely result against Staphylococcus aureus strain. In addition, compound 4b had the most potent anti-inflammatory activity with an inhibition rate of 47% at 1000 nM. Conclusion: The synthesized products4a-j possessed antibacterial activity (towards Escherichia coli microorganism; however, compounds 4c,4e, and 4j took the highest activity) and anti-inflammatory activity (compound 4b showed the highest inhibition rate).

Fluorine substituted thiomethyl pyrimidine derivatives as efficient inhibitors for mild steel corrosion in hydrochloric acid solution: Thermodynamic, electrochemical and DFT studies

Three new 5-fluoro-2- methylthio substituted pyrimidine derivatives have been synthesized and characterized by 1H NMR spectroscopy and Mass spectrometry. Corrosion inhibition characteristics of the synthesized pyrimidine derivatives have been studied on mild steel (MS) in 0.5 M hydrochloric acid solution at various temperatures (303−333 K) using mass loss and electrochemical techniques. The obtained weight loss, electrochemical impedance and potentiodynamic polarization data indicate that the corrosion inhibition efficiency is directly proportional to concentration of the inhibitors. The Adsorption process on MS surface obeyed Langmuir isotherm model. Scanning electron microscopy (SEM) was used to characterize surface morphology of the MS specimen in absence and presence of pyrimidine derivatives. Density functional theory (DFT) calculations using B3LYP functional with 6-311+G (d,p) level was used to establish the relationship between molecular structure and corrosion inhibition efficiency. Electrochemical analysis indicated that pyrimidine derivatives inhibit the corrosion by adsorbing on the metal surface. Mixed-type of corrosion inhibition activity with anodic predominance was proposed by polarization studies.

Facile CAN catalyzed one pot synthesis of novel indol-5,8-pyrimido[4,5-d]pyrimidine derivatives and their pharmacological study

Abstract In the present work a novel series of indol-5,8-pyrimido[4,5-d]pyrimidine derivatives (4a-l) have been synthesized by Biginelli reaction of barbituric/thiobarbituric acid, substituted indole-3-carboxaldehyde and substituted aryl amines in aqueous ethanol using 10 mol% CAN as a catalyst. The synthesized compounds (4a-l) were evaluated for in vitro antibacterial and anticancer activities. In addition to this, in silico molecular docking studies was also performed to predict the binding interactions of synthetic molecules with appropriate target molecules in connection to their antimicrobial and anti-cancer effects. Among the compounds tested, compounds 4d, 4 g and 4 h were found to have effective antibacterial activity against the tested pathogens. The cytotoxicity studies of synthesized pyrimidine derivatives were found to be effective against K-562, HeLa, MCF-7 and Hepg-2 cancer cell lines.

SYNTHESIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF PYRIMIDINE DERIVATIVES

Objectives: Synthesis, characterization, and evaluation of antimicrobial activity of novel pyrimidine derivatives containing O, N, and S in the ring.
 Methods: Pyrimidine derivatives were prepared in three steps. In the first step, chalcones containing -NO2 functional group were synthesized using Claisen-Schmidt condensation of aromatic aldehydes with 2-acetyl pyridine/3-acetylpyridine in methanol in the presence of aqueous NaOH. In the second step, -NO2 group was reduced to -NH2 group. Resulting compounds containing NH2 functional group were reacted with different dichlorothienopyrimidines and dichlorofuropyrimidines in the presence of N,N-diisopropylethylamine to obtain pyrimidine derivatives.Antibacterial and antifungal activity of pyrimidine derivatives were studied in vitro.
 Results: Pyrimidine derivatives were synthesized and purified using flash column chromatography. Purity of synthesized pyrimidines was determined by high-performance liquid chromatography. Pyrimidines were characterized by elemental analysis, infrared, nuclear magnetic resonance, and mass spectral analysis. Analytical data of synthesized pyrimidines supported the proposed structures. Significant antibacterial and antifungal activity were observed in the synthesized pyrimidine derivatives.
 Conclusion: Antibacterial and antifungal activity of the newly synthesized pyrimidine derivatives will definitely inspire future researchers for the preparation of new analogs.

Aspartic-acid-loaded starch-functionalized Mn–Fe–Ca ferrite magnetic nanoparticles as novel green heterogeneous nanomagnetic catalyst for solvent-free synthesis of dihydropyrimidine derivatives as potent antibacterial agents

Mn0.5Fe0.25Ca0.25Fe2O4@starch@aspartic acid magnetic nanoparticles (MNPs) as a new green nanocatalyst were designed and synthesized by a coprecipitation procedure. The structure of the aspartic-acid-loaded starch-functionalized Mn0.5Fe0.25Ca0.25Fe2O4 nanoparticles was evaluated by powder X-ray diffraction analysis, Fourier-transform infrared spectroscopy, vibrating-sample magnetometry, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and thermogravimetric analysis. The ferrite magnetic nanoparticles exhibited superparamagnetic nature with saturation magnetization of 35 emu/g. The impact of the MnFeCaFe2O4@starch@aspartic acid MNPs was investigated in synthesis of 3,4-dihydropyrimidine derivatives by multicomponent reaction between thiourea/urea, acetylacetone, and various aryl aldehydes under solvent-free conditions. Facile workup, short reaction time, superb yield, and use of a reusable catalyst are the advantages of this method. The magnetic nanocatalyst was easily recovered and reused six times without considerable reduction in its catalytic activity. The in vitro antibacterial activity of all synthesized pyrimidine derivatives was studied by agar well diffusion assay technique against four pathogenic bacterial strains, namely Staphylococcus aureus (ATCC no. 6538) and Staphylococcus epidermidis (ATCC no. 12228) as Gram-positive bacteria and Pseudomonas aeruginosa (ATCC no. 9027) and Escherichia coli (ATCC no. 8739) as Gram-negative bacteria. All compounds exhibited greater antibacterial activity compared with the reference drug ciprofloxacin.

Antimicrobial activity and acetylcholinestrase inhibition of novel synthesized pyrimidine derivatives versus Candida albicans trafficking to brain and kidney.

The expedient fungi Candida albicans (C. albicans) is able to thrive in many host niches including blood stream, skin, mucosal surfaces, and different body organs. Herein, the assessment of novel synthesized pyrimidine derivatives as anti fungal agent was investigated. Female albino mice were injected intraperitoneally by C. albicans (1.5 × 106 CFU). infected Mice then subjected to treatment with two different doses which was low (50 mg/kg) and high one (200 mg/kg) of diflucan in addition to the newly synthestic compounds (2-(4- (Pyridine- 2- yl) aminosulfonyle phenylamino) - 6 -(naphthalene-2- yl)-4-(pyridine-2- yl) n - 3 carbonitril) and (2-(4-(Pyrimidine-2- yl) aminosulfonyle phenylamino)- 6 -(naphthalene-2- yl)- 4 -(pyridine-2- yl) pyridine-3- carbonitril) donated as (C1 & C2, respectively). Three weeks later gene expression of renal alpha smooth muscle actin (α-SMA) and of cyclooxygenase-2 (COX-2) protein expression were assessed as well as serum malondialdehyde (MDA) and total antioxidant capacity in both kidney and brain tissues. Furthermore, acetylcholinestrase activity was assessed. Candida albicans significantly elevated serum MDA. On the other hand, C. albicans injection revealed a significantly reduction in total antioxidant capacity in kidney as well as in brain tissue. Furthermore, acetylcholine assessment declared a significant elevation. All biochemical parametersۥ upset were modulated upon new synthesized compounds treatment. Molecular analyses declared a significant down - regulation in renal α -smooth muscle actin gene expression in addition to, a significant down- regulation in COX-2 protein expression. From data recorded, it could be concluded that, C2 in a dose 200 mg ∕kg noticeably declared a significant effect comparing with the other treated groups revealing its promising effect as anti-fungal agent.

Physicochemical properties of some pyrimidine derivatives in some organic solvents

Some physicochemical parameters such as density refractive index and conductance of some newly synthesized pyrimidine derivatives have been measured in N N dimethyl formamide chloroform and methanol at K It is observed that these studied parameters depend on the solvent and structure of compounds which may be due to different type of interactions