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The antibiotic resistance and biofilm formation by bacterial pathogens has led to failure in infections elimination. This study aimed to assess the antibacterial and anti-biofilm properties of novel synthesized nitroimidazole compounds (8a–8o). In this study, nitroimidazole compounds were synthesized via the A3 coupling reaction of sample substrates in the presence of copper-doped silica cuprous sulfate (CDSCS). Fifteen and two carbapenemase producing Escherichia coli and Klebsiella pneumonia (CP-E. coli and CP-K. pneumonia, respectively) and one methicillin-resistant Staphylococcus aureus (MRSA) and one methicillin-susceptible S. aureus (MSSA) plus standard strain of each isolate were included. The antibacterial effects of these compounds demonstrated that the lowest minimum inhibitory and bactericidal concentrations (MIC/MBC, respectively) levels corresponded to compound 8g against S. aureus (1/2 µg/mL) and K. pneumonia (8/32 µg/mL) standard and clinical strains and confirmed by in silico assessment. This was comparable to those of metronidazole being 32–128 µg/mL against K. pneumonia and 32–64 µg/mL against S. aureus. In comparison to metronidazole, against CP-E. coli, compounds 8i and 8m had significantly higher antibacterial effects (p < 0.001) and against CP-K. pneumonia, compounds 8a–8j and 8l–8o had significantly higher (p < 0.0001) antibacterial effects. Compound 8g exhibited significantly higher antibacterial effects against MSSA and compounds 8b (p < 0.001), 8c (p < 0.001), 8d (p < 0.001), 8e (p < 0.001) and 8g (p < 0.0001) exerted significantly higher antibacterial effects than metronidazole against MRSA. Moreover, potential anti-biofilm effects was corresponded to compounds 8a, 8b, 8c, 8e, 8f, 8g, 8i, 8k, 8m and 8n. Considering the antibacterial and anti-biofilm effects of novel synthesized compounds evaluated in this study, further assessments is warranted to verify their properties in vivo and clinical trials in the future. [ABSTRACT FROM AUTHOR]

Background: A series of coumarin-indole hybrids was synthesized as the new α-glucosidase inhibitors. The title hybrids were considered as α-glucosidase inhibitors because had two active pharmacophores against α-glucosidase: coumarin and indole. Methods: The thirteen various derivatives 4a–m were synthesized, purified, and fully characterized. These compounds were evaluated against α-glucosidase in vitro and in silico. In silico pharmacokinetic studies of the most potent compounds were also performed. Results: Most of the title compounds exhibited high anti-α-glucosidase activity in comparison to standard drug acarbose. In particular, the phenoxy derivative 4d namely 3-((1H-indol-3-yl)(3-phenoxyphenyl)methyl)-4-hydroxy-2H-chromen-2-one showed promising activity. This compound is a competitive inhibitor against α-glucosidase and showed the lowest binding energy at the α-glucosidase active site in comparison to other potent synthesized compounds and acarbose. Conclusion: Compound 4d can be a lead compound for further structural development to obtain effective and potent α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

The preparation, characterization and application of hydroxyapatite silica propyl bis aminoethoxy ethane cuprous complex (HASPBAEECC) as a novel hybrid nano-catalyst for synthesis of new benzimidazole-1,2,3-triazole hybrid analogues as promising antifungal agents have been described. HASPBAEECC is fully characterized by different microscopic, spectroscopic and physical techniques, including scanning electron microscopy (SEM), transmission, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA) and FT-IR. The ʻClick̕ Huisgen cycloaddition reaction of N-propargyl benzimidazole with diverse azidoalkyls in a THF-water media at ambient temperature provides the products in good-to-excellent yields using HASPBAEECC. HASPBAEECC is proved to be a stable, low cost, reusable and environmentally benign nanohybrid catalyst. The target compounds were screened against some pathogenic fungal comprising Candida albicans, Candida krusei, Candida parapsilosis, Aspergillus fumigatus and Aspergillus flavus in which it was determined that compounds 11f and 11 h have displayed promising antifungal activity similar to fluconazole as a reference drug. HASPBAEECC is a novel hybrid nano-catalyst for highly efficient synthesis of new benzimidazole-1,2,3- triazole hybrid analogues as antifungal agents. [ABSTRACT FROM AUTHOR]

The presilylation of purine and pyrimidine nucleobases as well as other related N-heterocycles with HMDS utilizing chitosan–silica sulfate nanohybrid (CSSNH) is described. CSSNH is proved to be a useful, highly efficient and eco-friendly heterogeneous nanohybrid catalyst for silylation of nucleobases. The presilylated nucleobases then underwent the reaction with different sources of carbon electrophiles to afford the desired N-alkyl-substituted derivatives in good-to-excellent yields. CSSNH exhibits several advantageous involving ease of handling and preparation, low cost, reusability and environmental benignity. These unique properties render the CSSNH to be an ideal candidate for use in green industrial processes. [ABSTRACT FROM AUTHOR]

The design, synthesis, antinociceptive and β-adrenoceptor blocking activities of several eugenyloxy propanol azole derivatives have been described. In this synthesis, the reaction of eugenol with epichlorohydrin provided adducts 3 and 4 which were N-alkylated by diverse azoles to obtain the eugenyloxy propanol azole analogues in good yields. Adducts 3 and 4 were also reacted with azide ion to obtain the corresponding azide 6. The 'Click' Huisgen cycloaddition reaction of 6 with diverse alkynes afforded the title compounds in good yields. The synthesized eugenyloxy propanol azole derivatives were in vivo studied for the acute antinociception on male Spargue Dawley rats using tail-flick test. Compounds 5f, 5g, 7b and 11a exhibited potent analgesic properties in comparison with eugenol as a standard drug. In addition, all compounds were ex vivo tested for β-adrenoceptor blocking properties on isolated left atrium of male rats which exhibited partial antagonist or agonist behaviour compared to the standard drugs. The molecular docking study on the binding site of transient receptor potential vanilloid subtype 1 (TRPV1) has indicated that like capsaicin, eugenyloxy propanol azole analogues exhibited the strong affinity to bind at site of TPRV1 in a "tail-up, head-down" conformation and the presence of triazolyl moieties has played undeniable role in durable binding of these ligands to TRPV1. The in silico pharmacokinetic profile, drug likeness and toxicity predictions carried out for all compounds determined that 5g can be considered as potential antinociceptive drug candidate for future research. [ABSTRACT FROM AUTHOR]

Toxicopathological effects of herbs have always been a major concern. There is scant information available about the toxicopathological effects of Calotropis procera (C. procera) in the fetus. Since the chick embryo is a suitable preclinical model to evaluate the toxicopathological effects of chemicals, the objective of this study is to evaluate the lesions of various dosages of C. procera using a chick embryonic model. Fertile chicken eggs were divided into three equal treatment groups; phosphate buffered saline-injected group and C. procera-injected groups whose individuals were treated with C. procera extract at dosages of 50 or 100 mg/kg egg-weight. Embryos were re-incubated post-treatment and allowed to develop until day 18, after which they were examined for macroscopic and microscopic lesions. Although the embryos which were treated with 50 mg/kg egg-weight of C. procera extract macroscopically were normal as well as the controls, those treated with 100 mg/kg egg-weight were stunted and under developed. Microscopic evaluations showed that in embryos treated with 100 mg/kg egg-weight of C. procera, the brain was congested, and severe dilation of central veins and sinusoids as well as hepatocellular degeneration was occurred in liver. Moreover, the kidney and lung were under-developed, but the structure of the heart was normal. Based on our findings, C. procera at dosage of 100 mg/kg is toxic to the chick embryo or/maybe to human fetus during growing period. Further studies are needed to clarify the toxic effects of this plant on the development of fetus. [ABSTRACT FROM AUTHOR]

The design, synthesis and biological study of several novel 1,2,3-triazolyl $$\upbeta $$ -hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl)-9 H-carbazole. The 'Click' Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9 H-carbazole with diverse $$\upbeta $$ -azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram-negative bacteria. In particular, 1-(4-((9 H-carbazol-9-yl) methyl)-1 H-1,2,3-triazol-1-yl)-3-butoxypropan-2-ol ( 10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between $$\upbeta $$ -hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a-10n as potential lead antifungal agents for future investigations. [ABSTRACT FROM AUTHOR]

Highly efficient protocol for one-pot N-alkylation of nucleobases using alcohol in ionic liquid media as a straightforward route to access acyclic nucleoside was described. In this protocol purine, pyrimidine as well as azole derivatives underwent the N-alkylation reaction with primary or secondary alcohols using TsCl/TEA/KCO in bmim[Br] to afford the products in good-to-excellent yields. The influence of factors in this method including the type of ionic liquid, base and sulfonating agents was discussed. The current method showed an appropriate selectivity in reaction with primary alcohols in comparison with secondary alcohols. This protocol is mild, safe and easy to apply; moreover, it is quite compatible with eco-friendly and green chemistry protocols, since the exploitation of toxic and hazardous materials such as DMF and alkyl halides has been prevented. [ABSTRACT FROM AUTHOR]

A facile and selective one-pot N-acylation of nucleobases via carboxylic acids using cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) is described. In this protocol, the reaction of diverse carboxylic acids with pyrimidine and/or purine nucleobases is efficiently achieved in the presence of cyanuric chloride and NaH/EtN in DMF/MeCN (1:1, v/v) to afford the corresponding N-acyl nucleobases in good yields. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The synthesis and biological effects of 15 novel azole-bonded $$\upbeta $$ -hydroxypropyl oxime $$O$$ -ethers have been described. In this synthesis, the oximation of aromatic ketones followed by an $$O$$ -alkylation reaction with epichlorohydrin and/or epibromohydrin led to the corresponding $$O$$ -oxime ether adducts. Subsequently, the attained $$O$$ -oxime ether adducts were used to synthesize the target molecules after treating them with the appropriate azole derivatives. The in vitro antifungal and antibacterial activities of title compounds were obtained against several pathogenic fungi, Gram-positive and/or Gram-negative bacteria. Benzophenone $$O$$ -2-hydroxy-3-(2-phenyl-1 $$H$$ -imidazol-1-yl) propyl oxime and 9 $$H$$ -fluoren-9-one $$O$$ -2-hydroxy-3-(2-phenyl-1 $$H$$ -imidazol-1-yl)propyl oxime proved to have considerable antifungal activity against Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum. These two compounds demonstrated comparable antifungal activity to clotrimazole and fluconazole (standard drugs). All compounds were also tested against Escherichia coli and Staphylococcus aureus as Gram-negative and Gram-positive bacteria, respectively, and their activities were compared to gentamycin and ampicillin (reference drugs). In general, marginal antibacterial activity against tested bacteria was observed for the title compounds. A molecular docking study is also discussed for the two most potent compounds against fungi. The docking study reveals a considerable interaction between the two most potent compounds and the active site of Mycobacterium P450DM. Moreover, these two compounds are much strongly bound to the active site of Mycobacterium P450DM compared to fluconazole. [ABSTRACT FROM AUTHOR]

The syntheses and biological studies of O-oxime ethers having α-amino acid residues as new analogs of IPS-339 have been described. In this synthesis, the reaction of fluorene and/or benzophenone O-oxime with epichlorohydrin or epibromohydrin afforded the corresponding O-oxime ether adducts. The N-alkylation of amino acid with O-oxime ether adducts led to synthesis of new analogs of IPS-339. The products were examined for their cardiovascular property. It was demonstrated that 2-(3-(9 H-fluoren-9-ylideneaminooxy)-2-hydroxypropylamino)-3-methyl-butanoic acid as the most potent compound substantially reduces the heart rate of dogs. Compounds were also evaluated for their in vitro antibacterial activity against some Gram-negative and Gram-positive bacteria. The antibacterial screening proved the considerable antibacterial activity against both groups of bacteria. The docking analysis demonstrated the appropriate fitting of 2-(3-(9 H-fluoren-9-ylideneaminooxy)-2-hydroxy-propylamino)-3-methyl-butanoic acid in human β-adrenergic receptor active site. Potential drug toxicity for some active compounds has also been predicted. [ABSTRACT FROM AUTHOR]

A mild, efficient, and selective protocol for the one-pot $$N$$ -alkylation of sulfonamides with alcohols using triphenylphosphine and carbon tetrachloride is described. In this method, treatment of alcohols with a mixture of triphenylphosphine, carbon tetrachloride, and potassium sulfonylamide salts in refluxing anhydrous DMF furnishes the corresponding $$N$$ -alkyl sulfonamides in good to excellent yields. This protocol is highly efficient for various structurally diverse alcohols and potassium sulfonylamide salts. In this paper the influence of solvents and various reagents as sources for electrophilic-halogen instead of carbon tetrachloride in combination with triphenylphosphine have been examined. This protocol demonstrates the selectivity between primary and secondary alcohols. A plausible mechanism for this protocol has been described. [ABSTRACT FROM AUTHOR]

A facile and highly convenient base-free protocol for the chemoselective preparation of 1,2-diol mono-esters is described. In this method, the regioselective ring opening of epoxides with carboxylic acids in the presence of [bmim]Br furnishes the corresponding 1,2-diol mono-esters in excellent yields. This method is efficient for various structurally diverse epoxides and carboxylic acids and it can be efficiently applied for the scale up synthesis of 1,2-diol mono-esters in reasonable to good yields. [bmim]Br remarkably influences the reaction progress and acts as both solvent and catalyst in this protocol. [ABSTRACT FROM AUTHOR]

In the current study, two novel classes of the carboacyclic nucleosides having miconazole-like scaffolds as imidazole- and pyrimidine-based compounds were examined for their cytotoxic properties. The aim was to establish a relation between cytotoxic activity and nature of the synthetic compounds. While Escherichia coli (DH5α) and human erythromyeloblastoid leukemia cell line (K562) were the target cells, depending on the type of substitution made, ranges of antibacterial and antineoplastic activities were observed. Also the electron-donating and electron-accepting properties of the ligands were proved to play a crucial role in their cytotoxic activities. Accordingly, the substitutions associated with the marked improvement of cytotoxic activities can be considered as the significant point in construction of new generation of either antibacterial or antineoplastic agents. [ABSTRACT FROM AUTHOR]

The novel copper(II) Schiff base complex was synthesized. Density functional theory calculations at the B3LYP (6-311G**/LANL2DZ) level of theory have been carried out to investigate the structure and geometry of the Schiff base ligand and its copper complex. IR spectra data (experimental and theoretical) show that the ligand Schiff base is coordinated to the copper ion in a bi-negative tetradentate manner with NNOS donor sites. From the theoretical data, it was found that the geometrical structure of this complex is distorted square planar. In continue, a safe, efficient, and improved procedure for synthesis of 1, 2, 3-triazole derivatives by immobilized [CuL] on silica is described. Terminal alkynes reacted with organic azides in the presence of a novel copper(I) catalyst, which is prepared by in situ reduction of the copper(II) Schiff base complex with ascorbic acid, in H2O/THF at room temperature. Moreover, immobilized [CuL] on silica was approved to be a chemically and thermally stable catalyst that can be reused for several times with no significant loss in catalytic activity. The in vitro antifungal activities of title compounds were studied against Candida albicans (ATCC 10231), Candida krusei (ATCC 6258) and Aspergillus niger (ATCC 16404). Two compounds containing 2-(4-((((diphenylmethylene)amino)oxy)methyl)-1H-1,2,3-triazol-1-yl)-1-phenylethan-1-one and 2-(4-((((9H-fluoren-9-ylidene)amino)oxy)-methyl)-1H-1,2,3-triazol-1-yl)-1-phenylethan-1-one proved to have potent antifungal activity against Candida albicans and Candida krusei. A molecular docking study is also discussed for all synthesized compounds. The docking study demonstrated a significant interaction between the two most potent compounds and the active site of Mycobacterium P450DM. [ABSTRACT FROM AUTHOR]

A facile and simple protocol for the 'Click' cycloaddition of organic azides with terminal alkynes catalyzed by immobilized [Cu(cdsalMeen)] on silica as a new and convenient heterogeneous catalyst is described. In this synthetic methodology, [Cu(cdsalMeen)]-SiO catalyzes 1,3-dipolar Huisgen cycloaddition of different functionalized β-azido alcohols and alkynes in the presence of ascorbic acid and a solution of THF/HO (2:1, V/V) at room temperature. Good to excellent yields of β-hydroxytriazolylalkyl derivatives were afforded using [Cu(cdsalMeen)]-SiO. Immobilization of [Cu(cdsalMeen)] on silica was approved as a chemically and thermally stable catalyst that can be reused for many consecutive trials without a significant decline in its reactivity. Graphical Abstract: [ABSTRACT FROM AUTHOR]