Synthesis,Characterization, Antimicrobial Activity Screening,and Molecular Docking Study of Pyrimidine Carbonitrile Derivatives

Russian Journal of Organic Chemistry - The present work describes the synthesis of 4-amino-6-(2-benzylidenehydrazinyl)-pyrimidine-5-carbonitrile derivatives,...     

Synthesis,Antimicrobial Activity and Molecular Docking Study of Thiazole Derivatives

The reaction of 4‐thiochromane thiocarbohydrazone with a series of hydrazonoyl halides in dioxane in the presence of triethylamine afforded novel thiochromane derivatives incorporating 1,3‐thiazole moiety. The structure of the latter compounds was established by elemental analysis and spectral technique and by their chemical transformation. Moreover, the antimicrobial activity of the newly synthesized compounds was screened and the results showed that some compounds have higher activity than the applied fungicide and bactericide. The antimicrobial activity of the most active compounds was interpreted by molecular docking study.     

Lipase-Catalyzed Synthesis,Antioxidant Activity,Antimicrobial Properties and Molecular Docking Studies of Butyl Dihydrocaffeate

Green chemistry approaches, such as lipase-catalyzed esterification, are promising methods for obtaining valuable chemical compounds. In the case of the use of lipases, unlike in aqueous environments, the processes of the ester bond formations are encountered in organic solvents. The aim of the current research was to carry out the lipase-catalyzed synthesis of an ester of dihydrocaffeic acid. The synthesized compound was then evaluated for antioxidant and antimicrobial activities. However, the vast majority of its antioxidant activity was retained, which was demonstrated by means of DPPH· (2,2-diphenyl-1-picrylhydrazyl) and CUPRAC (cupric ion reducing antioxidant capacity) methods. Regarding its antimicrobial properties, the antifungal activity against Rhizopus oryzae is worth mentioning. The minimum inhibitory and fungicidal concentrations were 1 and 2 mM, respectively. The high antifungal activity prompted the use of molecular docking studies to verify potential protein targets for butyl ester of dihydrocaffeic ester. In the case of one fungal protein, namely 14-α sterol demethylase B, it was observed that the ester had comparable binding energy to the triazole medication, isavuconazole, but the interacted amino acid residues were different.     

Synthesis,Structural Characterization,Molecular Docking,Thermal Studies,and Antimicrobial Activity of Ni(II) Binuclear Complexes

Russian Journal of General Chemistry - A new hexadentate ligand, 3,3′-{(1E,1′E)-[(4-chloro-1,2-phenylene)bis(azaneylylidene)]bis(methaneylylidene)}bis(2-hydroxybenzoic acid) (H4L) was...     

Synthesis,Characterization, Enzyme Inhibitory Activity,and Molecular Docking Analysis of a New Series of Thiophene-Based Heterocyclic Compounds

Russian Journal of Organic Chemistry - 1-Phenyl-3-(thiophen-2-yl)-1H-pyrazole-5-carboxamide derivatives were designed and evaluated for their in vitro enzyme inhibitory activities against...     

New Pyridopyrimidone Derivatives: Synthesis,Molecular Docking Studies,and Potential Anticancer Activity

Russian Journal of General Chemistry - A new series of pyrido[2,3-d]pyrimidones incorporated pyrazoles and fused triazoles are synthesized and tested in vitro for cytotoxic effect against cancer...     

Synthesis,Biological Activity,and Molecular Docking Assessment of Some New Sulfonylated Tetrazole Derivatives

The designed molecular structures have been subjected to computational analysis for calculating their physicochemical properties and drug likeness. The calculated data indicate that most of the compound possess the bioactivity score in the active zone. Synthetic approach to the target compounds is straightforward and easy to handle. Structures of the new compounds are supported by FT-IR, ¹H, and ¹³C NMR, and mass spectra. Antimicrobial tests of the products against pathogens (S. aureus, S. epidermidis, E. coli, and P. mirabilis) indicate the products as active or highly active. Their cyto-toxicity is determined to be 92–98% at concentration of 3.125 µmol/L. The molecular docking analysis carried out for the target compounds against the receptor Glc-N-6P exhibits low binding energy and various binding sites of those.

     

Novel Triazole-, Oxadiazole-, and Pyrazole-Nicotinonitrile Hybrids: Synthesis,DFT Study,Molecular Docking,and Antimicrobial Activity

Russian Journal of General Chemistry - The present study is devoted to functionalization of ethyl 2-{[3-cyano-6-(4-cyanophenyl)-4-(2,4-dichlorophenyl)pyridin-2-yl]oxy}acetate (1) by triazole-,...     

Synthesis,Antimicrobial Activity and Molecular Docking Studies of 1,3‐Thiazole Derivatives Incorporating Adamantanyl Moiety

Synthesis, characterization and investigation of antimicrobial activity of 11 novel adamantanyl‐thiazoles are presented. Their structures were determined using ¹H and ¹³C NMR, EI(+)‐MS, HRMS, and elemental analyses. Among the derivatives, compound 3c showed very strong activity, especially against Candida albicans ATCC 10231 and Candida parapsilosis ATCC 22019 with minimal inhibitory concentration (MIC) values ranging from 1.95 to 7.81 µg/ml. Compounds 3a and 3b showed good antifungal activity. Among the examined compounds, the widest spectrum of antibacterial activity possessed 3f that showed good activity, especially against Staphylococcus epidermidis ATCC 12228, Micrococcus luteus ATCC 10240, Bacillus subtilis ATCC 6633 with MIC values ranging from 31.25 to 62.5 µg/ml. Molecular docking studies of all compounds on the active sites of microbial enzymes indicated possible targets sterol 14α‐demethylase, secreted aspartic proteinase (SAP), N‐myristoyltransferase (NMT), and topoisomerase II. Thiazoles 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k showed more favorable affinity to SAP and NMT than the native ligand.     

New Chalcone Derivatives with Schiff Base-Thiophene: Synthesis,Biological Activity,and Molecular Docking Studies

Russian Journal of General Chemistry - New thiophene chalcones 3, 6 and thiophene Schiff base-chalcone derivatives 4a–4d, 7a–7d are synthesized. Structures of the compounds are...     

New 1,3,4‐Thiadiazole Derivatives: Synthesis,Characterization, and Antimicrobial Activity

In the present study, 2,5‐bis(mercapto‐acetichydrazide)‐1,3,4‐thiadiazole ( 1 ) was utilized by different reagents, namely, ethoxymethylene malononitrile, ethoxymethylene ethyl cyanoacetate, triethyl orthoformate, phenyl isothiocyanate, carbon disulfide, isatin, acetophenone, cyclohexanone, different aldehydes, and different anhydrides, to yield a new series of 2,5‐disubstituted‐1,3,4‐thiadiazoles 2 – 18 . The chemical structure of these products was characterized by the spectral data IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. All the synthesized compounds were screened for their antibacterial activity.     

New 3,4-Annelated Coumarin Derivatives: Synthesis, Antimicrobial Activity, Antioxidant Capacity, and Molecular Modeling

Summary.  The one pot reaction preparation, spectral analysis, and molecular modeling experiments on the new 3,4-annelated coumarin systems with bioactivity associated structural features are described. These provided the insight into the equilibrium of the respective tautomeric forms making possible the reconciliation of previously published spectral data with the structure assignments as well as the correction of erroneously established structures. The synthesized compounds were tested in a standard disk diffusion assay and displayed strong to moderate antimicrobial activity, with a promising new lead prototype compound (7-amino-9-hydroxy-5-oxa-7a,8,11-triazacyclopenta[b]phenanthren-6-one (5)) possessing greater activity that the antibiotics Ampicillin and Nystatin. Antioxidant capacities of the compounds, determined spectrophotometrically using a phosphomolybdenum method, were greater, and in the case of compound 5 four times the activity of α-tocopherol acetate.     

New 3,4-Annelated Coumarin Derivatives: Synthesis, Antimicrobial Activity, Antioxidant Capacity, and Molecular Modeling

The one pot reaction preparation, spectral analysis, and molecular modeling experiments on the new 3,4-annelated coumarin systems with bioactivity associated structural features are described. These provided the insight into the equilibrium of the respective tautomeric forms making possible the reconciliation of previously published spectral data with the structure assignments as well as the correction of erroneously established structures. The synthesized compounds were tested in a standard disk diffusion assay and displayed strong to moderate antimicrobial activity, with a promising new lead prototype compound (7-amino-9-hydroxy-5-oxa-7a,8,11-triazacyclopenta[b]phenanthren-6-one (5)) possessing greater activity that the antibiotics Ampicillin and Nystatin. Antioxidant capacities of the compounds, determined spectrophotometrically using a phosphomolybdenum method, were greater, and in the case of compound 5 four times the activity of α-tocopherol acetate.     

New Biphenyl‐Based Bispyrazolines: Synthesis,Antimicrobial, and Docking Studies

In this study, a series of new bispyrazolines 8 ( a – f ) have been prepared from the cyclization reactions of bischalcones 7 ( a – f ) with phenyl hydrazine by refluxing under the alkaline alcoholic (KOH/EtOH) conditions. The O‐alkylation reactions of hydroxyl substituted chalcone 6 with different 1,ω‐dibromoalkanes in the presence of anhydrous potassium carbonate, tetrabutylammonium iodide, and dry acetone afforded the symmetrical new bischalcones 7 ( a – f ) in good yields. Chalcone 6 was realized by using the Claisen–Schmidt reaction of m‐hydroxyacetophenone with bipheny‐4‐carboxaldehyde. The various spectroscopic parameters such as IR, ¹H‐NMR, ¹³C‐NMR, and ESI‐MS have been thoroughly used for the structural interpretations of the newly prepared products. The in vitro antibacterial and antifungal activities of these compounds have been examined with the help of serial tube dilution method, and many of the tested products were found to be revealing the promising antimicrobial properties, which were evident from their minimum inhibitory concentration values. The molecular docking simulations of the synthesized substances have also been achieved to observe the structural association into the active site of the Escherichia coli FabH (PdB: 3IL9). Docking results of these compounds suggested that bispyrazoline 8b demonstrated the lowest binding energy that describes its higher stability into the pocket of E. coli. The excellent inhibitory activity of this bisheterocycle against E. coli FabH may be ascribed on the basis of hydrophobic and van der Waals interactions.     

Synthesis,Molecular Docking Study,and Cytotoxic Activity against MCF Cells of New Thiazole–Thiophene Scaffolds

Investigating novel compounds that may be useful in designing new, less toxic, selective, and potent breast anticancer agents is still the main challenge for medicinal chemists. Thus, in the present work, acetylthiophene was used as a building block to synthesize a novel series of thiazole-bearing thiophene derivatives. The structures of the synthesized compounds were elucidated based on elemental analysis and spectral measurements. The cytotoxic activities of the synthesized compounds were evaluated against MCF-7 tumor cells and compared to a cisplatin reference drug, and against the LLC-Mk2 normal cell line using the MTT assay, and the results revealed promising activities for compounds 4b and 13a. The active compounds were subjected to molecular modeling using MOE 2019, the pharmacokinetics were studied using SwissADME, and a toxicity radar was obtained from the biological screening data. The results obtained from the computational studies supported the results obtained from the anticancer biological studies.     

Novel Galactopyranoside Esters: Synthesis,Mechanism, In Vitro Antimicrobial Evaluation and Molecular Docking Studies

One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6-O-valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di-O-valeroate and 6-O-valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6-O- and 2,6-di-O-valeroate were converted into several 2,3,4-tri-O- and 3,4-di-O-acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus), which clearly supported the in vitro antifungal results. In particular, MDG ester 7–12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.     

Synthesis,Antimicrobial Activity,and Molecular Docking of Benzoic Hydrazide or Amide Derivatives Containing a 1,2,3-Triazole Group as Potential SDH Inhibitors

Main observation and conclusion The present study was carried out in an attempt to synthesize a new class of antimicrobial agents containing a 1,2,3-triazole mo...     

Synthesis,Anti-lung Cancer Activity and Docking Study of New Organic Compounds

Novel organic compounds(1～8) were designed, synthesized and characterized by IR, ~1H NMR, H RMS, and single-crystal X-ray crystallography. The anticancer activities of these compounds were investigated against four human lung cancer cells(H20, H2227, H69 and H524) by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT) assay. Furthermore, by taking compounds 1 and 5 as representatives, molecular docking studies supported the biological assay data, suggesting that compared with 1, compound 5 has stronger interaction with protein.     

Synthesis and Biological Activity of New Resveratrol Derivative and Molecular Docking: Dynamics Studies on NFkB

Resveratrol (RVS) is a naturally occurring antioxidant, able to display an array of biological activities. In the present investigation, a new derivative of RVS, RVS(a), was synthesized, and its biological activity was determined on U937 cells. It was observed that RVS(a) showed pronounced activity on U937 cells than RVS. RVS(a) is able to induce apoptosis in tumor cell lines through subsequent DNA fragmentation. From the EMSA results, it was evident that RVS(a) was able to suppress the activity of NFkB by interfering its DNA binding ability. Furthermore, the molecular interaction analysis (docking and dynamics) stated that RVS(a) has strong association with the IkB-alpha site of NFkB compared with RVS; this binding nature of RVS(a) might be prevent the NFkB binding ability with DNA. The present findings represent the potential activity of propynyl RVS on U937 cells and signifying it as a one of putative chemotherapeutic drugs against cancer.     

Synthesis,Characterization,Nematocidal Activity and Docking Study of Novel Pyrazole-4-carboxamide Derivatives

A series of novel 1-methyl-3-(trifluoromethyl)-~1H-pyrazole-4-carboxamide derivatives were designed based on our previous work and synthesized. All these title compounds were confirmed by NMR and MS. The primarily nematocidal activity results indicated that some of them exhibited good control efficacy against the tomato root-knot nematode disease caused by M. incognita. The docking results indicated that compound 6n interacts with amino acid residue Trp 279 of Ach E via hydrogen bond and amino acid residue Trp 84 of Ach E via π-π interaction.