Computational Chemical Study Research Articles

Synthesis and antimicrobial activity of thiophene-based heterocycles derived from thiophene-2-carbohydrazide.

Aim: Thiophene-based heterocycles were synthesized and evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, Clostridium difficile and Candida albicans strains. Methods: Antimicrobial activity was determined using the broth microdilution method. Results: Spiro-indoline-oxadiazole 17 displayed the highest activity against C. difficile while having no effects against other bacterial strains. Compounds 8 and 16 displayed strong effects against TolC, an outer membrane protein, mutant E. coli. The results of computational chemical study and outcomes of experiments were in good agreement. A molecular docking study was conducted using a molecular operating environment to simulate the binding energies of the potent compounds with D-alanine ligase protein. Conclusion: This study suggests that spiro-indoline-oxadiazole 17 could be a good anticlostridial agent.

A computational study of the potential bioactivity of hibiscus and garcinia acids against SARS-COV-2

A computational chemical study was conducted on the diastereoisomers of hibiscus acid (HA) and garcinia acid (GA), investigating their docking capabilities with the main protease (6LU7) of SARS-CoV-2. Electrostatic potential mappings unveiled negative charges associated with the carboxyl and hydroxyl groups positioned at C-2 and C-3 for both hibiscus and garcinia acids. However, the presence of more negative potentials around C-2 and C-3 of hibiscus acid, compared to garcinia acid, suggests that substituents in the (2S,3R) configuration possess a stronger electron-attracting capacity than those in the (2S,3S) configuration. Molecular docking studies indicated that both hibiscus acid and garcinia acid bind to the main protease through the catalytic pocket. Nonetheless, molecular dynamics simulations revealed that only HA remained bound to the active site for 100 ns with an RMSD of less than 1 ?, whereas GA dissociated from the complex within the initial 16 ns. These findings illuminate the differential binding behaviors of the two compounds, with implications for potential therapeutic interventions against SARS-CoV-2. These findings shed light on the differential binding behaviors of the two compounds, holding implications for potential therapeutic interventions against SARS-CoV-2.

Synthesis, computational chemical study, antiproliferative activity screening, and molecular docking of some thiophene-based oxadiazole, triazole, and thiazolidinone derivatives.

Thiophene-2-carbohydrazide was used in this study to produce some thiophene-containing oxadiazole, triazole, and thiazolidinone derivatives through reactions with various carbon-centered electrophiles. Besides, the hydrazone obtained was allowed to react with mercaptoacetic acid and acetic anhydride to construct thiazolidinone and oxadiazole derivatives. The results of computational chemical study and outcomes of the experiments were in good agreement. The in vitro antiproliferative activity of the produced compounds was examined against two human cell lines namely, breast adenocarcinoma (MCF7) and colon cancer (HCT116) cell lines using doxorubicin as a reference anticancer agent. The produced hydrazones and spiro-indolin-oxadiazole derivatives were the most potent against the two cancer cell lines. The molecular docking was conducted to demonstrate the binding energies of produced substances toward human carbonic anhydrase IX (CA IX) protein. The binding energies of these ligands were near to that of the co-crystallized ligand (9FK). Compound 11b exhibits a binding energy of -5.5817 kcal mol-1, indicating tight binding to some key nucleobases and amino acids of CA IX protein, while compound 11a displays a higher binding energy compared to the reference ligand (9FK). This suggests that compounds 11b and 11a display a notably strong binding affinity towards the human carbonic anhydrase IX (CA IX) protein. ADME profiles of the potent compounds including physicochemical characteristics, lipophilicity, and drug-likeness were predicted.

One-pot synthesis, computational chemical study, molecular docking, biological study, and in silico prediction ADME/pharmacokinetics properties of 5-substituted 1H-tetrazole derivatives

An efficient synthesis of 5-substituted 1H-tetrazoles was successfully achieved through one-pot multi-component condensation reactions of some aromatic aldehydes or indolin-2,3-dione with malononitrile and sodium azide using diverse reaction conditions to obtain considerable product yields. Furthermore, it has been achieved for the first time to construct desired products under neat condition. Molecular docking studies with CSNK2A1 receptor disclosed the lowest binding energy displayed by the dimethoxyphenyl derivative 4c with − 6.8687 kcal/mol. The synthesized tetrazoles were screened for their in-vitro cytotoxic activity against epidermoid cancer cell line (A431) and colon cancer line (HCT116) with respect to normal skin fibroblast cell line (BJ-1) using MTT assay, and antimicrobial activity against the bacteria: K. pneumonia, S. aureus, and the fungi: Candida albicans, as well as their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay. In addition, the toxicity of tetrazole derivative was assessed by determination of their approximate lethal dose fifty (LD50), calculated via an oral administration to rats, through measurement of ALT and bilirubin levels in serum. The antitumor results can suggest that the potent tetrazole derivative namely, 3-(3,4-dimethoxyphenyl)-2-(1H-tetrazol-5-yl)acrylonitrile (4c) could be a potential drug against epidermoid carcinoma. The antioxidant results indicated to tetrazoles exhibited great antioxidant properties even at very low doses. A molecular dynamics simulation was performed for the synthesized compounds (ligands) to investigate their tendency for binding with the active sites of protein.

Experimental and computational chemical studies on the corrosion inhibitive properties of metamizole sodium pharmaceutical drug compound for CS in hydrochloric acid solutions

The effect of sodium metamizole as a corrosion inhibitor for carbon steel (CS) in 1 M hydrochloric acid at various concentrations was studied by using chemical (weight loss, WL) and electrochemical [electrochemical frequency modulation (EFM), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP)] methods. The results of WL showed that the effectiveness of sodium metamizole as a CS preservative in a hydrochloric acid solution at room temperature raised by improvement of the concentration of the inhibitor and reached 82.87% at 300 ppm and 25 °C. The effect of temperature on the CS was studied and the thermodynamic parameters of activation and adsorption were computed and discussed. The results showed that the inhibition efficiency (IE) decreases with increasing temperature, suggestive of physisorption. This was collaborated by values of activation energy, which are all below 80 kJ mol−1 and free energy which are below 20 kJ mol−1. The adsorption mechanism was coherent with Langmuir adsorption model. Results of the PDP revealed that the inhibitor was adsorbed on CS surface by mixed type of behavior. Furthermore, EIS revealed the dip in the values of double-layer capacitance and improvement in the charge transfer resistance with increased dose of sodium metamizole. Surface examinations were performed using altered techniques. The theoretical studies were calculated to confirm the validity of the practical results and the results of both were compared with each other, demonstrating the validity of the results obtained.

Network Pharmacological Analysis of the Red Sea Sponge Hyrtios erectus Extract to Reveal Anticancer Efficacy of Corresponding Loaded Niosomes.

In this study, the LC-HRMS-assisted chemical profiling of Hyrtios erectus sponge led to the annotation of eleven major compounds (1–11). H. erectus-derived crude extract (HE) was tested in vitro for its antiproliferative activity against three human cancer cell lines, Hep-G2 (human liver cancer cell line), MCF-7 (breast cancer cell line), and Caco-2 (colon cancer cell line), before and after encapsulation within niosomes. Hyrtios erectus extract showed moderate in vitro antiproliferative activities towards the studied cell lines with IC50 values 18.5 ± 0.08, 15.2 ± 0.11, and 13.4 ± 0.12, respectively. The formulated extract-containing niosomes (size 142.3 ± 10.3 nm, PDI 0.279, and zeta potential 22.8 ± 1.6) increased the in vitro antiproliferative activity of the entrapped extract significantly (IC50 8.5 ± 0.04, 4.1 ± 0.07, and 3.4 ± 0.05, respectively). A subsequent computational chemical study was performed to build a sponge–metabolite–targets–cancer diseases network, by focusing on targets that possess anticancer activity toward the three cancer types: breast, colon, and liver. Pubchem, BindingDB, and DisGenet databases were used to build the network. Shinygo and KEGG databases in addition to FunRich software were used for gene ontology and functional analysis. The computational analysis linked the metabolites to 200 genes among which 147 genes related to cancer and only 64 genes are intersected in the three cancer types. The study proved that the co-occurrence of compounds 1, 2, 3, 7, 8, and 10 are the most probable compounds possessing cytotoxic activity due to large number of connections to the intersected cytotoxic genes with edges range from 9-14. The targets possess the anticancer effect through Pathways in cancer, Endocrine resistance and Proteoglycans in cancer as mentioned by KEGG and ShinyGo 7.1 databases. This study introduces niosomes as a promising strategy to promote the cytotoxic potential of H. erectus extract.

Experimental and computational chemical studies on the corrosion inhibition of new pyrimidinone derivatives for copper in nitric acid

Inhibition of copper corrosion by some pyrimidinone derivatives, namely; (E)-N-(3-((1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)diazenyl)-2,5-diethoxyphenyl)benzamide (MA-975) and(E)-6-(4-((4-chlorophenyl)diazenyl)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)-1,3 dimethylpyrimidine-2,4(1H,3H)-dione (MA-978C) in 1.0 M nitric acid (HNO3) was studied using weight loss (WL), electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization (PP) measurements. The efficiency of inhibition increases as the concentration of inhibitor increases, and it also increases as the temperature increases. With the addition of the examined inhibitors, significant corrosion protection was obtained, and (MA-975) showed a very promising % IE (89.59%) at 21 × 10−6 M using the (WL) method. The polarization data revealed that these compounds act as mixed-type compounds and are adsorbed on the copper surface following Langmuir adsorption isotherm forming a protective thin film protecting the metal in the corrosive media. Scanning electron microscopy (SEM) and Energy Dispersive X-ray were used to examine the surface morphology of copper samples. Quantum calculations and Monte Carlo simulation techniques were applied with informative yields and the results matched the experimental findings.

Experimental and computational chemical studies on the corrosion inhibitive properties of carbonitrile compounds for carbon steel in aqueous solutions

The present work aims to study 6-amino-4-aryl-2-oxo-1-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile derivatives namely: 6-Amino-2-oxo-1,4-diphenyl-1,2-dihydropyridine-3,5-dicarbonitrile (PdC-H), 6-Amino-2-oxo-1-phenyl-4-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile (PdC-Me) and 6-Amino-4-(4-hydroxyphenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-3,5-dicarbonitrile (PdC-OH) as corrosion inhibitors to provide protection for carbon steel in a molar hydrochloric acid medium. Chemical measurements such as (weight loss) and electrochemical techniques such as (Potentiodynamic polarization, electrochemical impedance spectroscopy, and Electron frequency modulation) were applied to characterize the inhibitory properties of the synthesized derivatives. The adsorption of these derivatives on the carbon steel surface was confirmed by Attenuated Total Refraction Infrared (ATR-IR), Atomic Force Microscope (AFM), and X-ray Photoelectron Spectroscopy (XPS). Our findings revealed that the tested derivatives have corrosion inhibition power, which increased significantly from 75.7 to 91.67% on the addition of KI (PdC-OH:KI = 1:1) to inhibited test solution with PdC-OH derivative at 25 °C. The adsorption process on the metal surface follows the Langmuir adsorption model. XPS analysis showed that the inhibitor layer consists of an iron oxide/hydroxide mixture in which the inhibitor molecules are incorporated. Computational chemical theories such as DFT calculations and Mont Carlo simulation have been performed to correlate the molecular properties of the investigated inhibitors with experimental efficiency. The theoretical speculation by Dmol3 corroborates with the results from the experimental findings.

Computational Chemical Study of Pigment of Mangosteen (Garcinia mangostana) Rind Extract as Dye Compound in Dye-Sensitized Solar Cell (DSSC)

The electronic transition processes of α-mangostin and β-mangostin as dye compounds in DSSC and their ability to transfer electrons to semiconductors have been studied in theory. The research was carried out computationally using the NwChem application. The methods used are Density Functional Theory (DFT) for structure optimization and Time-Dependent DFT (TD-DFT) for electronic transitions. The results showed that the energy of HOMO β-mangostin was lower that it was more stable or easier to form bonds with semiconductors. Likewise, its LUMO energy is lower than α-mangostin that it is easier to inject electrons into the semiconductor. The energy difference of HOMO-LUMO β-mangostin is smaller than α-mangostin. This shows that β-mangostin is more easily excited or more efficient in exciting solar energy to convert it into electricity. This is consistent with the molecular spectra where λmaxβ-mangostin is at a higher wavelength. Orbital analysis shows electron injection of α-mangostin and β-mangostin into the semiconductor via double O atoms in each molecule. The injection is influenced by the bond length, where the bond length of α-mangostin to TiO2 is smaller than that of β-mangostin to TiO2.

Regioselective Synthesis, Spectroscopic Characterization, and Computational Chemical Study of Spiro[Indoline-3,4’-Pyrazolo[3,4-b] Pyridine Derivatives as Agrochemical Agents

Herein, new four-component domino reactions are described and utilized to synthesize spiro[indoline-3,4’-pyrazolo[3,4-b]pyridine derivatives via one-pot reaction. Different hydrazine derivatives such as hydrazine hydrate, methyl hydrazine, and phenylhydrazine were allowed to react with active methylene precursors (CH2CN) as malononitrile, ethyl cyanoacetate, isatin, and 1,3-dicarbonyl compounds in the presence of (+)-camphor-10-sulfonic acid (CSA) as the acid catalyst under microwave condition using water as the solvent. Two and three fused heterocyclic rings were obtained in a single synthetic operation with a facile work-up and less waste generation due to the absence of extraction and purification steps. Structural features of the obtained compounds were confirmed by utilizing elemental analyses, mass spectrometry, 1H-NMR, and 13C-NMR microanalyses. Insecticidal assessments for some of the synthesized pyrazole derivatives against the cotton leafworm Spodoptera littoralis were conducted. In addition, fungicidal activities against Rhizoctonia solani and Fusarium solani soil-borne fungi were also performed. The tested compounds showed poor insecticidal activity compared with the standard insecticide chlorpyrifos ethyl. Meanwhile, they showed remarkable fungicidal activity against tested pathogens. Analysis of the fungicidal study indicated that R. solani fungus was found to be more sensitive to the tested compounds than F. solani fungus. Some pyrazole derivatives particularly possessed close or even higher fungicidal activities than the standard fungicide Pencycuron (Monceren 25%WP). The density functional theory was then applied to explore the structural and electronic characteristics of these materials.

Synthesis, characterization, computational chemical studies and antiproliferative activity of some heterocyclic systems derived from 3-(3-(1,3-diphenyl-1H-pyrazol-4-yl)acryloyl)-2H-chromen-2-one

The key material, 3-(3-(1,3-diphenyl-1H-pyrazol-4-yl)acryloyl)-2H-chromen-2-one (3) was synthesized and its behavior toward malononitrile, hydrazine, thiourea, thiosemicarbazide, 2-aminoaniline, and 6-aminothiouracil was investigated aiming to synthesize a new series of pyrazole-based heterocycles, namely, pyranochromene, diazepine, pyrimidochromene, triazepine, benzodiazepine, pyrimidine, and pyrimidopyrimidine derivatives. Density functional theory based on quantum chemical computation outline the structure optimization of the intermediate that reacted to afford the desired product. The antiproliferative screening against HePG-2 and MCF-7 cancer cell lines disclosed that the most potent compounds against two cell lines were 9 and 17 as compared to doxorubicin which may be due to their presence in more tautomeric structures. Also, the minimized energy, dipole moment, ionization potential, transferred electrons, and charge density distribution revealed that the greater value of 0.126 and 0.8 for pyrazole derivatives 9 and 17, respectively, indicates the maximum transfer of electron and hence, greater tendency of scavenging radicals and rapidly reduce oxygen to superoxide.

Reactivity of 5-phenyl-3-[(2-chloroquinolin-3-yl)methylene] furan-2(3H)-one towards hydrazine and benzylamine: A comparative study

The reactivity of a 2-chloroquinolinylfuranone derivative 3 was investigated against two nitrogen nucleophilic reagents namely, hydrazine and benzylamine. It was found that the regioselectivity of the reaction products was mainly dependent on the nature of nucleophiles, reaction conditions, and solvent used. Therefore, hydrazinolysis of 3 afforded the corresponding acid hydrazide and pyridazinone derivatives depending on the reaction conditions. Otherwise, benzylamine reacted with 3 at different reaction aspects to provide N-benzylamide, N-benzylpyrrolone, and 2-benzylaminoquinolinyl-N-benzylpyrrolone derivatives. The chemical structures of all synthesized compounds were substantiated from their analytical as well as spectroscopic data. Based on the charge density calculations and computational chemical study which excluded the aza-Michael addition reaction and confirm the higher electron-deficiency of lactone carbonyl group than C2-quinoline position, it can be concluded that the C2-furanone becomes more susceptible to attack by the nucleophilic reagent, hydrazine and benzylamine.

Synthesis, Characterization, and Computational Chemical Study of Aliphatic Tricationic Surfactants as Corrosion Inhibitors for Metallic Equipment in Oil Fields.

Aliphatic tricationic surfactants were prepared by the esterification reaction, followed by a quaternization reaction to protect oil well facilities from corrosion problems. Microelemental analysis and Fourier transform infrared and 1H NMR spectroscopic techniques were performed to explore the obtained motifs. The performance of these amphiphiles as inhibitors for metallic S90 steel corrosion in formation water was investigated through electrochemical tests (potentiodynamic polarization and electrochemical impedance spectroscopy). The results revealed significant inhibition effectiveness improvement with increasing concentrations of these amphiphiles. Its maximum inhibition efficiency reaches 93.07% at 250 ppm for the compound (AED). Potentiodynamic polarization graphs demonstrated that tricationic amphiphiles behave as mixed-type inhibitors. In addition, the adsorption of the tricationic surfactant at the S90 steel surface followed Langmuir isotherm. Atomic force microscopy revealed that a protective layer formed at the surface of S90 steel caused the inhibition of corrosion. During the inhibition procedure of S90 steel corrosion, theoretical research has been performed to validate electrochemical experiments and to clearly demonstrate the mechanism of these amphiphiles. Finally, quantum chemical calculations were calculated to achieve the justification for the obtained empirical results.

Electron and Proton Transfers Modulate DNA Binding by the Transcription Regulator RsrR.

The [Fe2S2]-RsrR gene transcription regulator senses the redox status in bacteria by modulating DNA binding, while its cluster cycles between +1 and +2 states-only the latter binds DNA. We have previously shown that RsrR can undergo remarkable conformational changes involving a 100° rotation of tryptophan 9 between exposed (Out) and buried (In) states. Here, we have used the chemical modification of Trp9, site-directed mutagenesis, and crystallographic and computational chemical studies to show that (i) the Out and In states correspond to oxidized and reduced RsrR, respectively, (ii) His33 is protonated in the In state due to a change in its pKa caused by cluster reduction, and (iii) Trp9 rotation is conditioned by the response of its dipole moment to environmental electrostatic changes. Our findings illustrate a novel function of protonation resulting from electron transfer.

Design and Synthesis of Novel Sulfonamide-Derived Triazoles and Bioactivity Exploration.

Due to the incidence of resistance, a series of sulfonamide-derived 1,2,4- triazoles were synthesized and evaluated. The novel sulfonamide-derived 1,2,4-triazoles were prepared starting from commercial acetaniline and chlorosulfonic acid by sulfonylation, aminolysis, N-alkylation and so on. The antimicrobial activity of the synthesized compounds were evaluated in vitro by two-fold serial dilution technique. In vitro antimicrobial evaluation found that 2-chlorobenzyl sulfonamide 1,2,4-triazole 7c exhibited excellent antibacterial activities against MRSA, B. subtilis, B. typhi and E. coli with MIC values of 0.02-0.16 μmol/mL, which were comparable or even better than Chloromycin. The preliminary mechanism suggested that compound 7c could effectively bind with DNA, and also it could bind with human microsomal heme through hydrogen bonds in molecular docking. Computational chemical studies were performed on compound 7c to understand the structural features that are essential for activity. Additionally, compound 7c could generate a small amount of reactive oxygen species (ROS). Compound 7c could serve as a potential clinical antimicrobial candidate.

Theoretical investigation of the molecular structure and molecular docking of naratriptan

In this work, a computational chemical study of the naratriptan was carried out at the X/DGDZVP (where X = B3LYP, M06, M06L and ?B97XD) level of theory, the results suggest the existence of two possible conformers in the aqueous phase. The evaluation of the global and local reactivity descriptors indicates that both conformers show the same chemical behaviour. The docking studies reveal that both conformers bind to TYR359 residue of the 5HT1B receptor. Also, the first conformer binds to the receptor through THR209 and THR213 while the second one through THR209 and SER 212.

Experimental and computational chemical studies on the cationic furanylnicotinamidines as novel corrosion inhibitors in aqueous solutions

Abstract The corrosion inhibition action of three newly synthesized furanylnicotinamidine derivatives namely: 6-[5-{4(dimethylamino)phenyl}furan-2-yl]nicotinamidine (MA-1256), 6-[5-(4-chlorophenyl)furan-2-yl]nicotinamidine (MA-1266), and 6-[5-{4-(dimethylamino)phenyl}furan-2-yl]nicotinonitrile (MA-1250) on carbon steel (C-steel) was investigated in 1.0 mol⋅L−1 HCl solution by weight loss (WL), potentiodynamic polarization (PP), electrochemical impedance spectroscopy (EIS), and electrochemical frequency modulation (EFM) techniques. Morphological analysis was performed on the uninhibited and inhibited C-steel using atomic force microscope (AFM) and Infrared Spectroscopy (ATR-IR) methods. The effect of temperature was studied and discussed. Inspection of experimental results revealed that the inhibition efficiency (IE) increases with the incremental addition of inhibitors and with elevating the temperature of the acid media. The adsorption of furanylnicotinamidine derivatives on C-steel follows Temkin's isotherm. PP studies indicated that the investigated compounds act as mixed-type inhibitors and showed that p-dimethylaminophenyl furanylnicotinamidine derivative (MA-1256) was the most efficient inhibitor among the other studied derivatives with IE reached (95%) at 21 × 10−6 mol⋅L−1. MA-1266 is highly soluble in aqueous solution and has non-toxicity profile with LC50 > 37 mg·L−1. Thus, MA-1266 can be a promising green corrosion inhibitor candidate with IE > 91% at 21 × 10−6 mol⋅L−1. The experiments were coupled with computational chemical theories such as quantum chemical and molecular dynamic methods. The experimental results were in good agreement with the computational outputs.

Efficient Green Synthesis and Computational Chemical Study of Some Interesting Heterocyclic Derivatives as Insecticidal Agents

A series of 5,5‐diarylhydantoin (Dilantin) 3, 4, and 7, imidazole 1, 2, 5, 6, 8, and 9, thiazole 10–12, triazinthione 13, 15, 16, and 17, and thiadiazine 14 derivatives, containing diverse hydrophobic groups, were green synthesized through one‐pot stepwise reaction of aromatic aldehydes, vitamin B1, and nitrogen nucleophiles, for example, urea, thiourea, and thiosemicarbazide using grinding technique as well as conventional thermal methods. Such synthesized compounds have potent insecticidal activities; for example, compounds 4, 6, and 17 exhibited the highest insecticidal activity against both Plutella xylostella and Helicoverpa armigera with minimum inhibitory concentration values at 500 μg/mL and LD50 activities at 50 μg/mL. The density functional theory was then applied to explore the structural and electronic characteristics of these compounds. All the synthesized compounds have been characterized based on their elemental analyses and spectral data.

Regio-Selective Reaction, Spectroscopic Characterization and Computational Chemical Study of (Hesperidin) Hesperetin-7-O-Rutinoside Analogs as Antimicrobial Agents

Flavonoids display a strong antioxidant and radical scavenging activity and seem to beassociated with reduced danger for certain chronic diseases, the prevention of some cardiovascular sicknesses and certain types of cancerous processes [1-4]. Flavonoids show also antiviral, antimicrobial, and anti-inflammatory activities, helpful on capillary fragility and prevent human platelet aggregation, antiulcer and antiallergenic [5-11]. Though, the actual in vivo mechanism of action is largely unknown. Most studies have attentivein vitro tests at amounts much higher than in humans,however few clinical investigations have been carried out around the diseases [12].Additional clinical trials are required to evaluate a more precise correlation between flavonoids consumption and human health benefits [13]. The possible mechanism of potential experimentalactionhas been studied [14]. Citrus juices attitude among the most significant phenolicrich dietary sources [15].

Synthesis, spectroscopic characterization and computational chemical study of 5-cyano-2-thiouracil derivatives as potential antimicrobial agents

A series of 5-cyano-2-thiouracil derivatives, containing diverse hydrophobic groups in the 2-, 4- and 6-positions, were synthesized through one pot reaction of thiophene 2-carboxaldehyde, ethylcyanoacetate and thiourea using classic reflux-based method as well as microwave-assisted methods. Such prepared compounds were reacted with different electrophilic reagents to synthesize potent anti-microbial agents, e.g. 1,3,4-thiadiazinopyrimidine, hydrazide and triazolopyrimidine derivatives (compounds 4a-e, 9 and 10–12) respectively. The density functional theory (DFT) was then applied to explore the structural and electronic characteristics of these materials. It is found that compound 12 exhibited the highest antibacterial and antifungal activity against C. Albicans showing six-fold increasing biological affinity compared to that of Colitrimazole drug with MIC values 7.8 and 49 μg/mL, respectively. All the synthesized compounds have been characterized based on their elemental analyses and spectral data. Such compounds can be submitted to in vivo antimicrobial studies in future works.