Synthesis and antimicrobial activity of some novel benzofuran based 1,2,3-triazoles

In the present study, a series of novel {6-[(1H-1,2,3-triazol-4-yl)methoxy]-3-methylbenzofuran-2-yl}(phenyl)methanones (7a–7o) have been synthesized using click chemistry approach. The structures of all newly synthesized compounds were characterized by FT-IR, ¹H and ¹³C NMR, and MASS spectral data. Most of products demonstrated high antimicrobial activity.

     

Synthesis and antimicrobial evaluation of some heterocyclic chalcone derivatives

Some new heterocyclic compounds containing isoxazole, pyrazole and oxadiazole ring systems were prepared from various chalcones. The synthesized compounds have been characterized by elemental analysis and spectral methods. These compounds were screened for their antimicrobial activities.     

Synthesis,biological evaluation,quantitative-SAR and docking studies of novel chalcone derivatives as antibacterial and antioxidant agents

In the present study, a series of chalcone derivatives including 17 new compounds were synthesised; their antibacterial activities against eleven bacteria, and their free radical-scavenging activities using DPPH were evaluated. All compounds showed significant antibacterial activities against both Gram-positive and Gram-negative bacteria. In particular, compound IIIf strongly inhibited Staphylococcus aureus (JMC 2151) and Enterococcus faecalis (CARS 2011-012) with MIC values of 6.25 µg mL^?1 and 12.5 µg mL^?1, respectively, which are comparable to that of the standard antibiotic, nalidixic acid. Compound IIIg also inhibited S. aureus with a MIC value similar to that of nalidixic acid (6.25 µg mL^?1). Furthermore, like nalidixic acid (MIC value of 25 µg mL^?1), compounds IIIa, IIIc and IIId inhibited Listeria monocytogenes (ATCC 43256) with MIC values of 25 µg mL^?1, 12.5 µg mL^?1 and 25 µg mL^?1, respectively. Quantitative structure-activity relationship (Q-SAR) studies using physicochemical calculations indicated that the antibacterial activities of chalcone derivatives correlated well with predicted physicochemical parameters (logP and PSA). Docking simulation by positioning the most active compound IIIf in the active site of the penicillin-binding protein (PBP-1b) of S. aureus was performed to explore the feasible binding mode. Furthermore, most of the compounds synthesised exhibited significant DPPH radical-scavenging activity, although compounds IIc and IIIc exhibited the greatest antioxidant activity with IC₅₀ values of 1.68 µM and 1.44 µM, respectively, comparable to that of the standard antioxidant, ascorbic acid (1.03 µM).     

Synthesis,anticancer evaluation,and docking studies of some novel azo chromene derivatives

We have described a simple, convenient, and high-yielding one-pot synthesis of novel azo chromene derivatives via a three-component reaction of various azo aldehydes with dimedone and malononitrile using 10 mol% of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst and ethanol as solvent at reflux condition. All the synthesized compounds have been characterized using Fourier-transform infrared spectroscopy (FT-IR), ¹H NMR, ¹³C NMR, and HR-MS spectra and molecular docking was performed to explore new inhibitors of human placental aromatase cytochrome P450 and cyclooxygenase-2 enzymes. Of all the compounds docked, compound (E)-2-amino-4-(4,4-dimethyl-2,6-dioxocyclohexyl)-6-((3-methoxyphenyl)diazenyl-4H-chromene-3-carbonitrile ( 4o ) showed good binding affinity with the active site of human placental aromatase cytochrome P450 enzyme (PDB: 3EQM) with inhibition constant (Ki) 1.66 nM and compound 4o also showed good binding affinity with the active site of cyclooxygenase-2 enzyme (PDB: 6COX) with inhibition constant (Ki) 367.17 pM. In vitro anti-cancer activity studies against MCF-7 cells were also performed for compounds 4o , anastrozole and celecoxib. Compound 4o showed an effective cytotoxicity at 19.8 μg/ml compared to anastrozole and celecoxib (24.7 and 26.2 μg/ml).     

Synthesis,characterization of novel quinoline-2-carboxamide based chalcone derivatives and their molecular docking,photochemical studies

Abstract

Novel series of quinoline-2-carboxamide based chalcone derivatives (5a–g) have synthesized and characterized using ¹H-NMR, 13C-NMR, Mass, and elemental analysis. In-silico molecular docking studies exhibited that synthesized compounds 5a and 5g are good binding energy (?8.46?kcal and ?9.46?kcal) toward the essential requirements of targeted compounds for EGFR receptor-bearing quinazoline inhibitor (PDB ID: 1M17(Lapitinib)). UV-Vis and fluorescence spectroscopy measurements provided a significant effect on the absorption, emission cyclic voltammetry (CV), and highest occupied molecular orbital (HOMO). Lowest unoccupied molecular orbital (LUMO) values of compound 5g are also confirmed band along with intramolecular charge transfer character (D-π-A). The red shift maxima (510?nm) the emission spectra in various solvents with increasing solvent polarity.     

Synthesis,in vitro evaluation,and molecular docking studies of benzofuran based hydrazone a new inhibitors of urease

This work has described the synthesis of novel class (1–25) of benzofuran based hydrazone. The hybrid scaffolds (1–25) of benzofuran based hydrazone were evaluated in vitro, for their urease inhibition. All the newly synthesized analogues (1–25) were found to illustrate moderate to good urease inhibitory profile ranging from 0.20 ± 0.01 to 36.20 ± 0.70 µM. Among the series, compounds 22 (IC₅₀ = 0.20 ± 0.01 µM), 5 (IC₅₀ = 0.90 ± 0.01 µM), 23 (IC₅₀ = 1.10 ± 0.01 µM) and 25 (IC₅₀ = 1.60 ± 0.01 µM) were found to be the many folds more potent than thiourea as standard inhibitor (IC₅₀ = 21.86 ± 0.40 µM). The elevated inhibitory profile of these analogues might be due to presence of dihydroxy and flouro groups at different position of phenyl ring B attached to hydrazone skeleton. These dihydroxy and fluoro groups bearing compounds have shown many folds better inhibitory profile through involvement of oxygen of dihydroxy groups in hydrogen bonding with active site of enzymes. Various types of spectroscopic techniques such as ¹H-, ¹³C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed compounds. To find SAR, molecular docking studies were performed to understand, the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data.     

Metal complexes of chalcone analogue: Synthesis,characterization, DNA binding,molecular docking and antimicrobial evaluation

A novel chalcone, namely 5‐(4‐(dimethylamino)phenyl)‐1‐(thiophen‐2‐yl)penta‐2,4‐dien‐1‐one, DMATP, and its complexes with nickel(II), vanadium(III), palladium(II) and platinum(II) metal ions were synthesized and characterized using a set of chemical and spectroscopic tools including elemental analysis, electrical conductance, magnetic susceptibility and spectral techniques. The interactions of the synthesized chalcone and its metal complexes with DNA were studied using steady‐state absorption and emission techniques as well as viscosity and electrochemical measurements. The obtained results confirm DNA intercalation. Additionally, theoretical studies were performed for all the investigated compounds using DFT/B3LYP calculations. The optimized geometries are found to be in good agreement with the suggested experimental structures. The bond lengths, bond angles, chemical reactivity, energy components, binding energy and dipole moment were evaluated. Also, theoretical infrared intensities and thermodynamic parameters for all compounds were calculated. Molecular docking calculations show that the Ni(II) complex exhibits the highest DNA binding activity, which agrees well with the experimental results. Finally, the compounds were screened for antimicrobial activity using several microorganisms.     

Synthesis of cicerfuran, an antifungal benzofuran, and some related analogues

Routes were investigated for the synthesis of cicerfuran, a hydroxylated benzofuran from wild chickpea implicated in resistance to Fusarium wilt, and some of its analogues. A novel method is described for the synthesis of oxygenated benzofurans by epoxidation and cyclisation of 2′-hydroxystilbenes. The stilbene intermediates required could be synthesised by palladium-catalysed coupling of styrenes with mono-oxygenated aryl halides but not with di-oxygenated aryl halides. Stilbenes corresponding to the latter were synthesised by Wittig reactions.     

Synthesis,biological evaluation,and molecular docking studies of novel pyrazole,pyrazoline-clubbed pyridine as potential antimicrobial agents

We have prepared 15 hybrid pyrazole, pyrazoline-clubbed pyridine–containing compounds (5a-o) and tested for their antibacterial and antifungal activities for the development of potential antimicrobial agents. The structures of this novel series were characterized by various spectral techniques like IR, ¹H NMR, ¹³C NMR, LC–MS, and elemental analysis. The synthesized compounds 5d, 5e, 5i, 5k, 5m, and 5o exhibited significant antimicrobial activity in the comparison of standard drugs. Molecular docking studies that have been carried out to emphasize the binding orientations of these molecules were in good compliance with crystal structure interactions. The predicted drug-likeness (ADME) properties were found to be in the acceptable range.     

Synthesis and antimicrobial activity of novel chalcone derivatives

A series of novel 3-[N, N-bis(2-hydroxyethyl)-amino]-chalcone derivatives 3a–3j were synthesized by the aldol condensation of [N, N-bis(2-hydroethyl)-3-amino]-acetophenone 2 with aromatic aldehydes. Their structures were further confirmed by ESI-HRMS, ¹H NMR, IR and elemental analysis. X-ray analysis reveals crystal 3b is a monoclinic system with P2₁/n space group. The antimicrobial activities of the newly synthesized chalcones in vitro were evaluated and the results indicated that most compounds presented moderate to good antimicrobial activities, especially the antifungal capability. Compounds 3a, 3d, 3f and 3g revealed obvious potency against Candida albicans with MIC values of 32 μg/mL, which were better compared with others.     

Synthesis,biological evaluation and molecular docking studies of novel benzimidazole derivatives

A novel series of N-substituted-benzimidazolyl linked para substituted benzylidene based molecules containing three pharmacologically potent hydrogen bonding parts namely; 2,4-thiazolidinedione (TZD: a 2,4-dicarbonyl), diethyl malonate (DEM: a 1,3-diester and an isooxazolidinedione analog) and methyl acetoacetate (MAA: a β-ketoester) (6a–11b) were synthesized and evaluated for in vitro α-glucosidase inhibition. The structure of the novel synthesized compounds was confirmed through the spectral studies (LC–MS, ¹H NMR, ¹³C NMR, FT-IR). Comparative evaluation of these compounds revealed that the compound 9b showed maximum inhibitory potential against α-amylase and α-glucosidase giving an IC₅₀ value of 0.54 ± 0.01 μM. Furthermore, binding affinities in terms of G score values and hydrogen bond interactions between all the synthesized compounds and the AA residues in the active site of the protein (PDB code: 3TOP) to that of Acarbose (standard drug) were explored with the help of molecular docking studies. Compound 9b was considered as promising candidate of this series.     

Synthesis,characterization, and antimicrobial evaluation of some novel anthracene heterocycles derivatives

A series of novel heterocyclic compounds containing anthracene moiety was synthesized. Reaction of (11R,15S)-9,10-dihydro-9,10-[3,4]furanoanthracene-12,14-dione with 2-cyanoacetohydrazide gave 2-cyano-pyrroloanthracen acetamide (1) , which acts as an adaptable material for the synthesis of new heterocyclic compounds. The synthesized compounds were examined for their antimicrobial activity against Escherichia coli and Staphylococcus aureus via p-iodonitrotetrazolium violet formazon assay. The results exhibited great activity against the tested strains with a minimum bactericidal concentration range from 0.636 to 3.8 mg/mL) and 0.159 to 3.6 mg/mL for E coli and S aureus, respectively. Interestingly, the highest activity was recorded for chromene derivative (6) against both strains.     

Synthesis,characterization, docking and antimicrobial studies of binol based amide linked symmetrical bistriazoles

The antimicrobial resistance and excessive use of modern drugs has hampered the treatment of infectious disease. Therefore, the development of new antibiotics with very good efficacy and lesser side effects is the focused area of medicinal chemists. In the present work, the design and copper (I) catalyzed click synthesis of some amide linked binol based 1,4-disubstituted 1,2,3-bistriazole hybrids from bisalkyne precursor is reported along with characterization of the newly synthesized bistriazoles with the support of IR, NMR and HRMS spectral techniques. The in vitro antimicrobial screening of these bistriazoles against selected bacterial (S. aureus, B. subtilis, and E. coli) and fungal (A. niger and C. albicans) strains signifies the importance of amide and triazole moiety in the final derivatives. The in silico docking studies further supports the antimicrobial results through various binding interactions with binding energies of compound 6f (1KZN: 9.7 kcal/mol) and 6h (4WMZ: 13,3 kcal/mol).     

A novel class of 1,4-disubstituted 1,2,3-triazoles: Regioselective synthesis,antimicrobial activity and molecular docking studies

A Novel class of 1,4-disubstituted 1,2,3-triazoles have been synthesized in good to excellent yields via Cu(I) accelerated azide-alkyne click chemistry reaction strategy. The newly synthesized compounds were assessed for their in vitro antimicrobial activity against five Gram-positive, seven Gram-negative bacteria and three fungi. Most of the synthesized compounds displayed significant activity against the tested Gram-positive and Gram-negative bacteria. Molecular docking study revealed that all docked compounds are bound efficiently with the active site of Topoisomerase IV (4EMV) receptor with the observed the free energy of binding from −7.79 to −9.44 kcal/mol. Interestingly, compound 13a forms four hydrogen bonds and displayed high binding energy (−9.44 kcal/mol) with the Topoisomerase IV (4EMV) receptor which correlated with their in vitro antimicrobial assays.     

Synthesis and in vitro cytotoxic evaluation of some novel hexahydroquinoline derivatives containing benzofuran moiety

A series of new ethyl 4-(2-(benzofuran-2-yl)-4-substituted-1,4,5,6,7,8-hexahydroquinolin-1-yl)-benzoate 3a–c was synthesized by Michael condensation of benzofuran chalcones 1a–c and cyclohexanone to give 2-(2-benzofuranyl)-4-substituted-5,6,7,8-tetrahydro-4-H -chromene 2a–c, followed by reaction of the latter with ethyl 4-aminobenzoate. Condensation of 3a–c with different amines afforded the corresponding amides 4a–e. On the other hand, upon treatment compounds 3a–c with hydrazine hydrate gave the benzohydrazide derivatives 5a–c. The reaction of compounds 5a–c with different thio/isocyanate gave the corresponding thiosemicarbazide and semicarbazide derivatives 6a–c. Meanwhile compounds 5a–c were reacted with ethyl cyanoacetate and different β-dicarbonyl compounds such as acetyl acetone, ethyl acetoacetate, and diethyl malonate to afford pyrazolyl derivatives 7a, b; 8a, b; 9a, b; and 10a–c, respectively. Moreover, 5a–c were reacted with carbon disulfide to synthesize the corresponding oxadiazolyl derivatives 11a–c, while their condensation with different aromatic aldehydes gave the corresponding Schiff bases 12a–d. Cytotoxic evaluation of some of the newly synthesized compounds against human hepatocellular carcinoma cell lines (HepG-2) revealed that the tested compounds produce promising inhibitory effect against the growth of HepG-2 cells with IC₅₀ values ranged from 11.9 to 19.3 µg/mL.     

Synthesis and antimicrobial activity of some netropsin analogues

Nine novel lexitropsins were synthesized by linking two netropsin-like moieties through three different dicarboxylic acids; 9,10-dihydro-2,7-phenanthrenedicarboxylic acid; [(3-[[(carboxymethyl)amino]carbonyl]benzoyl)amino]acetic acid and indole-2,5-dicarboxylic acid. The netropsin residues were modified by the use of N-isopentylpyrrole, 5-methylthiophene or 5-isopropylthiazole heterocyclic building blocks in place of the usual N-methylpyrrole. The compounds were tested against five gram-positive bacteria: Staphylococcus aureus, Streptomyces faecalis, methicillin resistant Staphylococcus aureus, Enterobacter cloacae, Mycobacterium fortuitum, three gram-negative bacteria: Klebsiella aerogenes, Proteus vulgaris, Escherichia coli and three fungi: Aspergillus niger, Candida albicans and Aspergillus nidulans. Some of the compounds showed significant inhibitory effects on the growth of the microorganisms.     

Design,synthesis, antimicrobial evaluation,and molecular docking studies of novel symmetrical 2,5-difunctionalized 1,3,4-oxadiazoles

A series of novel symmetrical 2,5-difunctionalized 1,3,4-oxadiazole derivatives of pharmacological significance have been synthesized. The obtained compounds were screened for their in vitro antimicrobial activities against Gram-negative (Escherichia coli and Salmonella typhimurium) and Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecium, and Streptococcus agalactiae or group B Streptococcus), as well as against the fungus Candida albicans. Although the synthesized compounds showed moderate antifungal activity against C albicans, they exhibited good-to-excellent antibacterial activities against several strains, than did standard drugs ampicillin and nystatin. In silico molecular docking in FabI enzyme active site gave information regarding the binding mode of the drug candidate at the molecular level.     

Synthesis,evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors

Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds (1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC₅₀?=?12.98 µM and IC₅₀?=?12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC₅₀?>?50 µM and, COX-2; IC₅₀?>?50 µM). The enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity.     

Synthesis and antimicrobial evaluation of tricyclic macrocycles containing a chalcone moiety

A series of new tricyclic macrocycles containing a chalcone moiety were synthesized from chalcones through alkylation using different dibromoalkanes. All the synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral data and evaluated for their in vitro antimicrobial activity.