In vitro pharmacological screening of three newly synthesised pyrimidine derivatives

The antibacterial and antifungal activities of three new pyrimidine derivatives, namely, 2,6-bis(4,6-dimethylpyrimidin-2-ylthio)benzene-1,4-diol (1),3,5-bis(4,6-dimethylpyrimidin-2-ylthio)-2-methylbenzene-1,4-diol (2) and 3,5-bis(4,6-dimethylpyrimidin-2-ylthio)-2-methoxybenzene-1,4-diol (3), synthesised by electrochemical method are presented here. The compounds were screened for their activities against Gram-positive and Gram-negative bacteria, Bacillus subtilis, Staphylococcusaureus, Escherichia coli and a pathogenic fungus Aspergillus niger. The results show that these compounds have significant activity against these bacteria and fungus. The minimum inhibitory concentration of compound 1 was determined as 62.5 μg/mL against B. subtilis, 125 μg/mL against E. coli and 250 μg/mL against S. aureus establishing its promising activities higher than susceptible ranges.     

Determination of Triazine and Chlorophenoxy Acid Herbicides in Natural Water Samples By Solid Phase Extraction and Quantitative Thin Layer Chromatography

Abstract

Atrazine, simazine, 2, 4-D, silvex, and 2, 4, 5-T, were determined in natural water samples at 10 ppb levels by solid phase extraction on disposable C₁₈ columns and TLC on preadsorbent silica gel layers impregnated with AgNO₃, exposure to UV light, and densitometric scanning. Recoveries ranged from 70 to 88% for the triazines and 93 to 100% for chlorphenoxy acid herbicides, with average CV values of 7 to 8%. Solid phase extraction proved to be an advantageous alternative to classical liquid-liquid partition for the analysis of water for these compounds by quantitative TLC.     

Two new phenolic compounds from the leaves of Alnus sibirica Fisch. ex Turcz.

Two new phenolic compounds, 4-O-glucopyranosyl-5-O-caffeoylshikimic acid (1) and 2,3-digalloyl oregonin (2), were isolated along with eight known phenolic compounds (3–10) from an 80% acetone extract of Alnus sibirica leaves. The chemical structures of these compounds were elucidated using 1D/2D nuclear magnetic resonance and high resolution-MS. The anti-oxidative activities of these compounds were determined by assaying their 1,1-diphenyl-2-picrylhydrazyl radical and nitroblue tetrazolium superoxide anion scavenging activity. All of the isolated phenolic compounds (1–10) exhibited potent anti-oxidative activities. In particular, 2 and 4, which are diarylheptanoids, and 10 which is ellagitannin exhibited excellent anti-oxidative activities with almost the same potency as that of the positive controls L-ascorbic acid and allopurinol.     

Isolation and structural elucidation of novel antimicrobial compounds from maggots of Chrysomyis megacephala Fabricius

The excretions/secretions from the maggot of Chrysomyis megacephala Fabricius are traditionally used to treat serious infections in China. In this study, bioassay-guided fractionation led to the isolation of three novel antibacterial compounds (1–3), including important fluorinated compounds (3 and 5), together with other nine known compounds from 70% methanol extract of C. megacephala. The structures of the new compounds were elucidated by NMR spectroscopic analysis and high-resolution mass spectroscopy. The antibacterial activities of the isolated compounds were evaluated using agar disc diffusion method. New compounds 1 and 2 exhibited moderate activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 250 μg mL^? 1. The most active compounds 3 and 5 displayed a broad spectrum of antimicrobial activity with an MIC of 125 μg mL^? 1 against G⁺ and G^?  bacteria. The structure of the above-mentioned novel compounds and their antimicrobial activities are herein reported for the first time from the natural product of insects.     

Isolation and identification of two new compounds from the Penicillium sp. SYPF7381

Abstract

Two new compounds, (7R, 2E, 5E)-3,5,7-trimethyl-2,5-octadienedioic-8-methyl ester (1) and neovasipyridone G (3), together with a new natural product compound (7R,2E,5E)-3,5,7-trimethyl-2,5-octadienedioic acid (2), and six known compounds (4–9) were isolated from Penicillium sp. SYPF7381. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 2 were determined by optical rotation. The absolute configuration of compound 3 was determined by means of electronic circular dichroism (ECD) calculation. In addition, the in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. Furthermore, the structure-antiinflammation activity relationships for these isolated compounds were summarized based on the experimental as well as the docking results.     

The cytotoxic activities of imidazole derivatives prepared from various guanylhydrazone and phenylglyoxal monohydrate

Abstract

A series of imidazole derivatives were synthesized from two-component condensation reaction of phenylgloxal monohydrate with guanylhydrazone. They were characterized by spectroscopic and analytical techniques. The in vitro anticancer evaluation of these compounds was done on human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines using the MTT assay method. Most of the newly synthesized compounds displayed cytotoxic activity against these cancerous cells. In fact, compounds 3a, 3e, and 3?h exhibited more cytotoxic activities than the positive control drugs, fluro-5, and irinocam, against the MCF-7 cell line. Almost all the compounds, except for three, 3b, 3d, and 3f, gave more cytotoxic results than cisplatin. Therefore, these compounds could be considered for further development as anticancer drug candidates.     

Synthesis and bioactivities of diamide derivatives containing a phenazine-1-carboxamide scaffold

Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by ¹H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC₅₀ value of 0.158 mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC₅₀ values of 0.067, 0.048 and 0.059 mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.     

A new bioactive diterpenoid from pestalotiopsis adusta,an endophytic fungus from clerodendrum canescens

Bioassay-guided fractionation of the culture extract of Pestalotiopsis adusta, an endophytic fungus isolated from the medicinal plant Clerodendrum canescens, led to the isolation of one new, (10S)-12,16-epoxy-17(15→16)-abeo-3,5,8,12,15-abietapentaen-2,7,11,14-tetraone (1), and four known diterpenoids, teuvincenone F (2), uncinatone (3), coleon U (4), coleon U-12-methyl ether (5). These structures were identified by using spectroscopic methods, including UV, MS, 1D and 2D NMR experiments. This is the first report of these compounds being isolated from a Pestalotiopsis species. The cytotoxic activities of the compounds were evaluated, and compounds 1 and 3 demonstrated cytotoxic activities against the HL-60 tumour cell line (IC₅₀ ＜ 20 μM).     

New phenyl derivatives from endophytic fungus Botryosphaeria sp. SCSIO KcF6 derived of mangrove plant Kandelia candel

Two new phenyl derivatives (1 and 3), along with two new natural products (4 and 5), and three known compounds (2, 6 and 7), were isolated from an endophytic fungus Botryosphaeria sp. SCSIO KcF6. The structures of these compounds 1–7 were elucidated by the extensive 1D and 2D-NMR and HRESIMS Data analysis, and compared with those of reported data. The absolute configuration of the compounds 1 and 3 were assigned by optical rotation and CD data. The isolated compounds were evaluated for their cytotoxic, anti-inflammatory (COX-2) and antimicrobial activities. Compound 3 exhibited a specific COX-2 inhibitory activity with the IC₅₀ value of 1.12 μM.     

Determination of Selected Quinolones and Fluoroquinolones by Use of TLC

Abstract

There are many different methods of quinolones determination. The most often used method of quinolones analysis is liquid chromatography. In this work some selected quinolones (cinoxacin, pipemidic acid) and fluoroquinolones (ofloxacin, pefloxacin) were separated with thin-layer chromatography (TLC). The two different mobile phases were used as follows: buffer solution (pH = 5.5)-methanol, 40:10 (v/v) and acetonitrile-water-acetic acid, 6:40:4 (v/v/v), respectively, for quinolones and fluoroquinolones. The following chromatographic parameters were calculated for these separations: R_F, ?R_F, R_M, and R_S. The possibility of qualitative determination of cinoxacin, pipemidic acid, ofloxacin, and pefloxacin using TLC was shown.     

Antimicrobial,DPPH scavenging and tyrosinase inhibitory activities of Thymus vulgaris,Helichrysum arenarium and Rosa damascena mill. ethanol extracts by using TLC bioautography and chemical screening methods

Antimicrobial, DPPH scavenging and tyrosinase inhibitory activities of Thymus vulgaris, Helichrysum arenarium and Rosa damascena Mill. ethanol extracts by using TLC bioautography and chemical screening methods. The ethanol extracts of Thymus vulgaris (Tv), Helichrysum arenarium (Ha) and Rosa damascena Mill. (Rm) (red) were screened for their antimicrobial, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and tyrosinase inhibitory activities. The test microorganisms included bacteria of Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923). Thin Layer Chromatography (TLC) - bioautography, disk diffusion and well diffusion methods were used for the antimicrobial activity assays. Rosa damascena Mill. extract was effective against E. coli and all plant extracts showed antimicrobial activity against S. aureus. The phenolic acids in the structure of the extracts were also identified by LC-MS analysis. Human blood agar well diffusion method and TLC-DPPH assays were used to identify the hemolytic and antioxidant activity of plant extracts, respectively, along with 10 compounds including phenolic acids as a standard. Among these compounds, caffeic acid (Rf = 0.68) was detected in all extracts while vanillic acid (Rf = 0.75), and gallic acid (Rf = 0.51) was found in Tv extract. Kojic acid (Rf = 0.36), on the other hand, was detected in Rm extract as a tyrosinase inhibitor. All plant extracts presented tyrosinase inhibitory activities on TLC-bioautography assay.     

Synthesis of 3-benzoyl-4-benzylfurans structural related to furolignans

Abstract

Furolignan-type natural products, possessing important biological properties, have been synthesized from a commercially available furan. The elaborated synthetic strategy is based on an innovative Friedel-Crafts reaction starting from an alcohol or a carboxylic acid and triflic anhydride as promoter. Through this synthetic strategy, furolignans having two different aryl groups have been obtained. The products have been evaluated for their antimicrobial properties on Gram positive and Gram negative bacteria, in order to compare their biological activities with those of natural analogues.     

Synthesis and Evaluation of Polyfunctionally Substituted Heterocyclic Compounds Derived from 2-Cyano-N-(5-pentadecyl-1,3,4-thiadiazol-2-yl)acetamide

Reaction of 5-pentadecyl-1,3,4-thiadiazol-2-amine 2 with ethyl cyanoacetate gave 2-cyano-N-(5-pentadecyl-1,3,4-thiadiazol-2-yl)acetamide 3, which was used to synthesize different heterocyclic derivatives with coumarin, pyrazole, thiazole, pyridine, pyrimidine, and thiophene rings. Propoxylation of these compounds by using 5 mol of propylene oxide produced nonionic surface active agents. Antimicrobial and surface activities were evaluated.     

Benzopyran derivatives from endophytic Daldinia eschscholzii JC-15 in Dendrobium chrysotoxum and their bioactivities

Five new benzopyran derivatives (2–6) and a new natural product (1) were isolated from endophytic Daldinia eschscholzii in Dendrobium chrysotoxum and determined as (R)-2,3-dihydro-2,5-dihydroxy-2-methylchromen-4-one (1), (2R, 4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol (2), (R)-3-methoxyl-1-(2,6-dihydroxy phenyl)-butan-1-one (3), 7-O-α-d-ribosyl-5-hydroxy-2-methyl-4H-chromen-4-one (4), 7-O-α-d-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one (5), daldinium A (6). These compounds were evaluated for their antimicrobial activity, anti-acetylcholinesterase, nitric oxide inhibition, anticoagulant, photodynamic antimicrobial activities and glucose uptake of adipocytes. Some compounds showed photoactive antimicrobial activities and glucose uptake stimulating activities.     

An efficient synthesis,spectral characterization,antimicrobial, and antioxidant activities of novel α-hydroxyphosphonates and α-hydroxyphosphinates

A simple, novel, and an efficient synthesis of α-hydroxy phosphonates (3a–d) and phosphinates (5a–f) has been accomplished from febuxostat aldehyde (1) with various dialkylphosphites (2) and dialkylphosphinates (4) in the presence of 1, 4-dimethylpiperazine as a strong base with good to excellent yields (78%–95%) is reported. The structures of the title compounds were established by elemental analysis and spectral data (IR, ¹H, ¹³C and ³¹P NMR, and LC-MS). All the title compounds (3a–d) and (5a–f) were tested for their antimicrobial and antioxidant activities. Bioassay results reveal that a few of the title compounds exhibited promising antimicrobial and antioxidant activities.     

Synthesis,characterization, and pharmacological evaluation of the proton transfer salts of 2-aminobenzothiazole derivatives with 5-sulfosalicylic acid and their Cu(II) complexes

Abstract

Two proton transfer compounds, formed between 2-aminobenzothiazole derivatives (2-aminobenzothiazole (abt) and 2-amino-6-ethoxybenzothiazole (EtOabt)) and 5-sulfosalicylic acid dihydrate (H₃ssa) as parent compounds, (Habt)⁺(H₂ssa)^? (1) and (HEtOabt)⁺(H₂ssa)^? (2) and their Cu(II) complexes (3 and 4, respectively) have been prepared and characterized using spectroscopic techniques. The single crystal X-ray diffraction method has been also applied to 3 and 4. Although 3 has a distorted octahedral form, 4 exhibits a distorted square pyramidal geometry. All compounds, including saline and diclofenac sodium as standards, have been evaluated pharmacologically for their anti-inflammatory and analgesic activities in rats and mice. Parent compounds (abt, EtOabt, and H₃ssa) 3 and 4 show significant anti-inflammatory and analgesic activities as compared with control compounds.     

Modeling of chromatographic retention of the selected antiarrhythmics and structurally related compounds in the hydrophilic interactions under the TLC and HPLC conditions

Abstract

High-performance liquid chromatography (HPLC) plays an important role in testing the pharmaceutically active compounds. In despite of the advantages of HPLC, thin-layer chromatography (TLC) retains its applicability to the different experimental tasks. The experimental conditions which allow hydrophilic interactions in the chromatographic system were tested in the HPLC and TLC systems for ivabradine, its related compounds, diltiazem and verapamil. Under the TLC conditions, retention behavior of the investigated compounds was tested on silica gel modified with cyanopropyl ligands as stationary phase and acetonitrile?+?methanol containing 25% v/v formic acid. Under the HPLC conditions, we used silica gel modified with cyanopropyl ligands as a column packing and the acetonitrile + 0.25% aqueous solution of formic acid as mobile phase. Retention behavior of the investigated analytes depending on the changing volume fractions of the mobile phase modifier was characterized both for TLC and HPLC data sets by the Soczewiński–Wachtmeister equation. Linear relationships were established between the retention coefficients characterizing the retention mechanism (R_M⁰/m, logk₀/m) and molecular properties of the investigated compounds. The Quantitative Structure Retention Relationship (QSRR) modeling was performed with the use of the stepwise multiple linear regression, in order to select molecular properties which influence retention.     

Synthesis and fungicidal activity of 1,3,4-oxadiazol-2-yl thioether derivatives containing a phenazine-1-carboxylic acid scaffold

To find new higher fungicidal activities lead compounds and develop new eco-friendly agrochemicals, natural product phenazine-1-carboxylic acid (PCA) as scaffold, a series of 1,3,4-oxadiazol-2-yl thioether derivatives was synthesized and bio-assayed. The results reveal that most target compounds possessed moderate to good fungicidal activities against R. solani, S. sclerotioru and P. oryzac Cavgra. Compounds 6n and 6o exhibit more than 90% bioactivity against S. sclerotioru. The EC₅₀ value of compounds 6n and 6o are 11.16 and 30.47?μM respectively, in particular, compound 6n show equal activity against S. sclerotioru to PCA (10.49?μM). This result provides a valuable lead compound for further studies.     

Ultrasound mediated green synthesis of rhodanine derivatives: Synthesis,chemical behavior,and antibacterial activity

A variety of rhodanine derivatives were synthesized via a three-component reaction of carbon disulfide, amines, and dialkyl acetylenedicarboxylate in polyethylene glycol under conventional stirring or ultrasound irradiation. The sonochemical-assisted procedure provides an improved and accelerated conversion when compared to the conventional reaction, with increased rate of reaction and quality of product obtained. The product formed, 2a, could be readily converted to bis-rhodanine under microwave conditions. Moreover, the pyranothiazoles 9a,b were prepared from the corresponding rhodanines 2a,b and malononitrile. Fifteen compounds were screened for their antibacterial activities against nine human, animal and plant pathogenic Gram-positive and Gram-negative bacteria using the agar well diffusion method. Out of these derivatives, compounds 2g and 2h were the most effective against all tested bacteria.     

Synthesis and Biological Activity of Novel Diphenyl N- Substituted Carbamimidoylphosphoramidate Derivatives

Abstract

An efficient synthesis of a series of novel diphenyl N-substituted carbamimidoyl phosphoramidate derivatives was accomplished in two steps. Diphenyl phosphorochloridate (1) was reacted with cyanamide (2) in the presence of 1,4–dimethylpiperazine as a base in THF at 50–55 °C to form an intermediate, diphenyl cyanophosphoramidate (3). Subsequently 3 was reacted with various aromatic/heterocyclic amines (4) in the presence of 1,4–dimethyl piperazine as a base at 55–60 °C to form the corresponding title compounds 5(a-k). The title compounds were tested for antiviral activity against Tobacco mosaic virus (TMV) in vitro, antibacterial and antifungal activities at two different concentrations of 50 and 100 μg/mL. The title compounds exhibited good antiviral and antimicrobial activities when compared to the standards.