Biological Evaluation of Some Antimicrobial Nano‐Materials

N‐(benzothiazol‐2‐yl)‐2‐(piperidin‐1‐yl)acetamide derivatives ( 1‐24 ) were obtained by the reaction of 2‐chloro‐N‐(benzothiazole‐2‐yl)acetamides with piperidine derivatives. The structures of the compounds were elucidated by ¹H‐NMR and mass spectral data and elemental analysis. The compounds were screened for their antimicrobial activities against pathogenic bacteria and Candida species. The compounds were also investigated for their cytotoxic properties using MTT assay. The microbiological results revealed that the compounds were more effective against fungi than bacteria. Among Candida species, C. utilis was the most susceptible fungus to compounds 7 and 11 . It is apparent that 2,6‐dimethylpiperidine group and chloro and methyl substituents on benzothiazole ring have an important impact on anticandidal activity. MTT assay indicated that the effective doses of these derivatives were lower than their cytotoxic doses.     

Synthesis and in vitro Study of Novel Methylenebis(phenyl- 1,5-benzothiazepine)s and Methylenebis(benzofuryl-1,5- benzothiazepine)s as Antimicrobial Agents

A series of methylenebis(phenyl-1,5-benzothiazepine)s 4 and methylenebis(benzofuryl-1,5-benzothiazepine)s 5 were prepared by the reaction of methylene-bis-chalcones 3 with 2-aminothiophenol for 4 and followed by the condensation with chloroacetone for 5. The structures of the synthesized compounds have been confirmed by their IR, 1H NMR, 13C NMR, MS and elemental analyses. All the synthesized compounds were tested for their antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. To elucidate the essential structural requirements for the antimicrobial activity, the preliminary structure-activity relationship has been described. Among the compounds tested, the dimeric compounds 4f, 4g, 5f and 5g were found to be most active against Bacillus subtilis, Bacillus sphaericus, Staphylococcus aureus, Klebsiella aerogenes and Chromobacterium violaceum. Similarly these dimeric compounds showed potent antifungal activity against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, and Trichophyton mentagrophytes. It is interesting to note that the dimeric compounds with substituents of heterocyclic ring at the 4th position of benzothiazepine system displayed notable antibacterial activity equal to that of streptomycin and penicillin. Further, the activity of all the dimeric compounds was compared with that of their monomeric compounds, and it is interesting to note that almost all the dimeric compounds showed enhanced activity than their monomeric compounds.     

Synthesis and optical behaviors of 2-(9-phenanthrenyl)-, 2-(9-anthryl)-, and 2-(1-pyrenyl)-1-alkylimidazole homologues

Eight 2-(9-phenanthrenyl)-, 2-(9-anthryl)- and 2-(1-pyrenyl)-1-alkyl-benzimidazole compounds, three 2-(9-anthryl)-1-alkylphenanthroimidazole compounds and five 4,5-diphenyl-1-alkyl-2-(9-anthryl)imidazole compounds were synthesized by alkylation reactions of the corresponding benzimidazole, phenanthroimidazole or imidazole compounds. 2-(10-Bromo-9-anthryl)-1-alkyl-benzimidazole compounds were prepared by bromination reaction of 2-(9-anthryl)-1-alkylbenzimidazole compounds. All the synthesized compounds were characterized by elemental analysis, ¹H NMR, ¹³C NMR, MS or HRMS; their absorption coefficients (), maximum absorption λ_amax, fluorescence emission maximum λ_em, Stokes shifts and fluorescence quantum yields (Φ_F) in ethyl acetate were determined; their fluorescent lifetimes (T₁ and T₂) were measured in ethyl acetate and in solid state, respectively. The crystal structure of 2-(9-anthryl)-1-n-butyl-4,5-diphenylimidazole (12a) was determined to be triclinic, space group P-1 types, using single crystal X-ray crystallography technique. The results showed that these compounds exhibited moderate fluorescence-emission abilities and higher solubility in most organic solvents than their corresponding starting materials. The relationships between the optical behaviors and structures for these compounds were discussed.     

Identification of O-Isobutyl S-(2-Diethylaminoethyl) Methylthiophosphonate Chemical Neutralization Products in Bitumen–Salt Matrices

Products of the chemical neutralization of O-isobutyl S-(2-diethylaminoethyl) methylthiophosphonate, a VX Group warfare agent, in bitumen–salt matrices were studied by gas chromatography–mass spectrometry. Forty-four compounds were characterized by their electron impact ionization mass spectra and gas chromatographic retention indices on standard nonpolar polydimethylsiloxane phases; seven of these compounds were determined as derivatives. The structures of 26 compounds were identified, including structures of 24 O-isobutyl S-(2-diethylaminoethyl) methylthiophosphonate neutralization products. To solve this problem, chromatographic retention indices of unknown compounds were evaluated using reference data for their structural analogues. Partition coefficients in the binary heterophase hexane–octanol system were determined for the major components.     

A new dihydrochalcone glycoside from the stems of Homalium stenophyllum

A new dihydrochalcone glycoside, phloretin-4-O-β-D-glucopyranoside (1), together with seven known flavonoids (2–8), were isolated from the stems of Homalium stenophyllum. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in the literature. The known compounds (2–8) were isolated from the genus Homalium for the first time. All compounds were evaluated for their antibacterial activities against six pathogenic bacteria in vitro.     

Synthesis of some novel 3,4,5-trisubstituted triazole derivatives bearing quinoline ring and evaluation of their antimicrobial activity

Abstract

Some new 3,4,5-trisubstituted 1,2,4-triazole derivatives were synthesized and studied for their antimicrobial activity. The lead compounds were obtained starting from 8-hydroxyquinoline and ethyl 2-chloroacetate. The obtained ester compound (1) first reacted with hydrazine hydrate (2) then with phenyl isothiocyanate (3). Ring closure by KOH led to 3-mercapto-1,2,4-triazole derivative (4). Lastly, it reacted with 2-chloro-N-(substituted (benzo)/thiazole)acetamide derivatives to obtain the final compounds (5a–j). The structural elucidation of the compounds was performed by ¹H NMR and ¹³C NMR spectroscopy and high resolution mass spectrometry techniques and elemental analysis. The synthesized compounds were investigated for their antimicrobial activities against seven bacteria and four fungi. As a result of the activity studies, it was observed that compounds N-(6-nitrobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5a) and N-(6-fluorobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5d) were the most active molecules. Also, the antifungal activity of the compounds was found to be higher than their antibacterial activity although lower than the standard drug’s potential. Additionally, the physicochemical properties of the compounds were calculated which were evaluated to be at a suitable range for oral administration.     

Synthesis and antimicrobial activity of a series of optically active quaternary ammonium salts derived from phenylalanine

We synthesized nine quaternary ammonium compounds (QUATs) starting from phenylalanine, N-alkyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromides, which were prepared as optically pure substances. Five compounds were prepared as S-enantiomers and four compounds as R-enantiomers. These compounds were evaluated by their activities against bacteria and fungi. Three microbial strains were used in the study: the gram-negative bacteria Escherichia coli, the gram-positive bacteria Staphylococcus aureus and the fungi Candida albicans. The activities were expressed as minimum bactericidal or fungicidal concentrations (MBC). The most active compounds were (2S)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide and (2R)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide, with MBC values exceeding those of commercial benzalkoniumbromide (BAB) used as standard. The relationships between structure and biological activity of the tested QUATs were quantified by the bilinear model (QSAR) and are discussed.     

Synthesis of isoniazid-1,2,3-triazole conjugates: Antitubercular,antimicrobial evaluation and molecular docking study

In the present study, a series of new isoniazid-1,2,3-triazole conjugates ( 5a-k ) was synthesized via click chemistry approach. The newly synthesized compounds were assessed for their in vitro antitubercular and antimicrobial activities. The compound 5g has displayed potent antitubercular activity against Mycobacterium tuberculosis H37Rv (Mtb) with MIC value 1.56 μg/mL. The active compounds were screened for their cytotoxicity profile by MTT assay against RAW 264.7 cell line. The four compounds have shown good in vitro antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study was accomplished to identify the probable mode of action of synthesized derivatives. These compounds have shown excellent binding affinity toward Enoyl-acp reductase (INHA) and DNA gyrase.     

Two New Cycloartane Triterpenoids from Kleinhovia hospita

Two new cycloartane triterpenoids, (23R)‐21,23:23,27‐diepoxycycloarta‐1,24‐diene‐3,27‐dione ( 1 ) and (3α)‐(α‐L ‐arabinopyranosyloxy)‐1α‐hydroxy‐23‐oxocycloartan‐28‐oic acid ( 2 ), together with six known pentacyclic triterpenoids, 3 – 8 , and five known C₂₉ steroids, 9 – 13 , were isolated from Kleinhovia hospita. The structures of these compounds were determined by analysis of their spectroscopic data. Moreover, the absolute configuration of 1 was confirmed by quantum‐chemical TDDFT calculation of its ECD spectrum. All compounds were evaluated for their cytotoxic activities against human colon carcinoma (HCT116) and gastric carcinoma (SGC7901) cell lines, and compounds 6, 7, 8, 11 , and 12 exhibited antiproliferative activities with IC₅₀ values ranging from 23.0 to 91.8 μM .     

Mass spectrometric behaviour of cyclopentane-and cyclohexane-condensed pyrimidinediones under electron impact

Mass spectral fragmentations of four cyclopentane-condensed cis-pyrimidinediones and of six cyclohexane-condensed cis- or trans-pyrimidinediones were examined using metastable ion analyses and exact mass measurements. The fragmentation patterns of all of these compounds were clearly different and also cis- and trans-fused isomers were easy to distinguish from each other by their mass spectra. In spite of the differences in their mass spectral fragmentations, all compounds formed phenylisocyanates (m/z 119 and 153) and anilines (m/z 93 and m/z 127), the structures of which were verified by collision-induced dissociation experiments.     

Dioxopiperazine Alkaloids Produced by the Marine Mangrove Derived Endophytic Fungus Eurotium rubrum

Cultivation of the fungal strain Eurotium rubrum, an endophytic fungus that was isolated from the inner tissue of stems of the mangrove plant Hibiscus tiliaceus, resulted in the isolation of two new dioxopiperazine derivatives, namely, dehydrovariecolorin L ( 1 ) and dehydroechinulin ( 2 ), together with eight known dioxopiperazine compounds including variecolorin L ( 3 ), echinulin ( 4 ), isoechinulin A ( 5 ), dihydroxyisoechinulin A ( 6 ), preechinulin ( 7 ), neoechinulin A ( 8 ), neoechinulin E ( 9 ), and cryptoechinuline D ( 10 ). The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data as well as by comparison with literature. Compounds 1, 2, 9 , and 10 were investigated for their α,α‐diphenyl‐β‐picrylhydrazyl (DPPH) radical‐scavenging activity. In addition, the new compounds, 1 and 2 , were evaluated for their cytotoxic activity against the P‐388, HL‐60, and A549 cell lines.     

Design,synthesis, preliminary pharmacological evaluation,and docking studies of pyrazoline derivatives

Ten derivatives of N1 substituted/unsubstituted 5-(4-chlorophenyl)-3-(2-thienyl) pyrazoline were synthesised from chalcone-like intermediate and substituted phenyl hydrazines, hydrazine hydrate, and semi/thiosemicarbazide. The chemical structure of compounds was confirmed by means of IR, ¹H NMR, mass spectroscopy, and elemental analysis. The antidepressant and anticonvulsant activities were investigated by Porsolt’s behavioural despair test (forced swimming) and maximum electroshock seizure test, respectively. Rota-Rod test was performed to assess any probable changes in motor coordination induced by the test compounds. Four compounds (IId, IIg, IIi, and IIj) exhibited good activity profile against depression and docking studies confirmed their consensual interaction with monoamine oxidase A. In addition, compounds IIc and IIe showed protection against MES-induced seizures.     

Aromatic compounds produced by endophytic fungi isolated from red alga Asparagopsis taxiformis - Falkenbergia stage

Endophytic fungi were isolated from red alga Asparagopsis taxiformis - Falkenbergia stage, collected from the Brazilian coast, and were identified as Annulohypoxylon stygium (AT-03) and A. yungensis (AT-06) based on their macro/micromorphological and molecular features. Bioassay-guided fractionation of the EtOAc extract from laboratory cultures of both strains yielded known compounds pyrogallol from A. stygium, (3R)-scytalone and (3R,4R)-4-hydroxy-scytalone from A. yungensis. Pyrogallol was active against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli strains. An inactive fraction from A. stygium afforded two additional compounds, (3R,4R)-3,4,5-trihydroxy-1-tetralone and tyrosol. Optically active compounds had their stereochemistry determined by circular dichroism (CD) spectroscopy.     

Intramolekulare Cycloadditionen in der Reihe der Binaphthyle

Intramolecular cyloadditions of binaphtyl compounds Three new bridged ketones, 7,8 and 9 , have been isolated in 44%, 3% and 19% yields respectively (Scheme 2) by heating 2,2′-bis-allyloxy-1,1′-binaphthyl ( 5 ) at 215° for 16 hours. These compounds could be epimerized about C(16) by bases, and in particular 9 yielded the new epimer 10 . The structures of the alcohols obtained by reduction of the keto group are also given (Scheme 2). The constitution of all compounds was derived from spectroscopic data, chiefly from their ¹H-NMR, spectra (tab. 2, 3 and fig. 1). The assignments were based on the observed long-range coupling constant between H(endo)-C(16) and H(endo)-C(5) in 7 and 10 and on the analysis of chemical shifts and coupling constants in both the ketones and their derivatives. Moreover, the structures of the compounds investigated have been proved by x-ray analysis of ketone 8 (chap. 3, fig. 2). The thermal conversion of binaphthylether 5 to the bridged ketones proceeds via an intramolecular Diels-Alder reaction, followed by Claisen rearrangement (Scheme 8). On heating, the bis-beta-methylallyl ether 20 yielded the ketone 21 and a small amount of the ether 23 (Schemes 5 and 7). Ether 23 and binaphthyl monoallyl ether 26 were converted thermally to the bridged ketones 31 (Scheme 7) and 27 (Scheme 6) respectively. In addition, 26 underwent an intramolecular ene-reaction to give the spiroketone 28 (Schemes 6 and 9). The structures of these compounds were also established, mainly by analysis of their ¹H-NMR. spectra.     

Functional polymers,XL. Syntheses of mono- and di(4-methoxy)benzotriazolesubstituted 2,4-dihydroxyaceto(or benzo)phenones

Eight benzotriazoles and (4-methoxy)benzotriazoles, mono- or di-substituted derivatives of 2,4-dihydroxyaceto(or benzo)phenone were synthesized by azo coupling of (4-methoxy)2-nitrobenzenediazonium chloride with 2,4-dihydroxyaceto(or benzo)phenone followed by reductive cyclization. Pure mono-substituted compounds were very difficult to prepare. Careful selection of thepH for the azo coupling and selection of the proper reagents for the reductive cyclization were essential. All compounds were characterized by their ultraviolet, infrared¹H and¹³C NMR spectra and their elemental analysis. These compounds have both the 2(2-hydroxyphenyl)2H-benzotriazole unit and a 2-hydroxyaceto(or benzo)phenone unit in the same molecule and are effective and useful ultraviolet absorbers.Dedicated to Prof. Dr.K. Komarek, Vienna, on the occasion of his 60^th birthday with best wishes.     

Rational eco-compatible synthesis and biological screening of new highly functionalized pyrido[2,3-a]carbazole derivatives: A novel class of antioxidant and anticancer agents

A solvent-free, one-pot, and operationally simple protocol was adopted to synthesize a new series of multifunctionalized pyrido[2,3-a]carbazole derivatives which were structurally characterized by FTIR, ¹H-NMR, ¹³C-NMR, and elemental analysis. The synthesized compounds were screened in vitro for their antibacterial activity and the compounds showed weak to moderate inhibition of bacterial growth. The antioxidant properties of the compounds were evaluated by their 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity and total antioxidant capacity. Moreover, the cytotoxic effect of the compounds was examined on cancerous cell lines MCF-7 and A549 under in vitro conditions and the results showed that the compounds exhibited significant anticancer activity. Furthermore, the morphological changes and apoptosis induction were studied by inverted light microscopy, acridine orange/ethidium bromide, and 4′,6-diamidino-2-phenylindole dihydrochloride fluorescence microscopic analyses. The results indicated that among pyridocarbazole compounds, 2-ethoxy-8-chloro-4-(thiophen-2′-yl)-5,6-dihydro-11H-pyrido[2,3-a]carbazol-3-carboxamide 6g could be exploited as significant antioxidant and anticancer agents.     

Two new isoaurones derivatives from Callistephus chinensis flower

Two new isoaurones derivatives were obtained from Callistephus chinensis flower. Their structures were elucidated on the basis of extensive spectroscopic analyses. Both of the new compounds were evaluated cytotoxic activity. Phytochemical investigation of Callistephus chinensis flower led to the isolation of two new isoaurones derivatives (Z)-4′,4,10-trihydroxy-siamaurone (1) and (E)-4′,4,10-trihydroxy-siamaurone (2). The structures of these new compounds were identified by the interpretation of spectroscopic data (mainly 1D and 2D NMR) and by comparison with data reported in the literature. Both of the new compounds were evaluated for their cytotoxicity.     

Novel O‐Alkylated Chromones as Antimicrobial Agents: Ultrasound Mediated Synthesis,Molecular Docking and ADME Prediction

In the development of novel antimicrobial agents, we synthesized novel O‐alkylated chromones 4a–f by ultrasound‐assisted method. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. All compounds were assessed in vitro for their efficacy as antimicrobial agents against four bacteria (Staphylococcus aureus , Bacillus subtilis , Escherichia coli , Pseudomonas aeruginosa ) and three fungi (Candida albicans , Candida glabrata , Candida tropicalis ). In particular, compounds 4a , 4b , 4d , 4e , and 4f exhibited potent antimicrobial activity. Molecular docking study was used to rationalize binding interaction at the active site, and the result showed good binding interaction. The compounds were also processed for in silico ADME prediction, and the result showed that compounds could be exploited as an oral drug candidate.     

Ultrasound‐assisted Synthesis of Novel Pyrazole and Pyrimidine Derivatives as Antimicrobial Agents

Herein, we report a convenient and facile methodology for the synthesis of new series of pyrazole and pyrimidine derivatives 2a – f and 3a – f under ultrasound irradiation. Pyrazole and pyrimidine derivatives have been synthesized in better yields and shorter reaction times compared with the conventional method. The chemical structures of all the synthesized compounds were elucidated by their IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. Further, the target compounds were screened for their antimicrobial activity against four bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa) and two fungi (Candida albicans, Aspergillus niger). In particular, compounds 2a , 2d , 2e , 3a , 3e , and 3f exhibited potent antimicrobial activity.     

Pyrido[1,2‐a]pyrimidin‐4‐ones: Ligand‐based Design,Synthesis, and Evaluation as an Anti‐inflammatory Agent

In the present study, a series of novel pyrido[1,2‐a]pyrimidin‐4‐one derivatives ( 1 – 45 ) were synthesized, characterized, and evaluated for their anti‐inflammatory activity. The structures of all newly synthesized compounds were confirmed by ¹H NMR, ¹³C NMR, mass spectroscopy, and C, H, and N analyses. Preliminary these newly synthesized compounds were evaluated for their in vitro cyclooxygenase (COX)‐2/COX‐1 inhibitory activity. The celecoxib, a COX‐2 inhibitor, was used as a reference standard drug. In this inhibitory study, compounds 42 , 43 , 44 , and 45 were found to have significant in vitro inhibitory profile as compared with the reference drug. These compounds were then subjected to their in vivo anti‐inflammatory assay by using carrageenan‐induced rat paw edema method in next level of screening. Later, these same compounds were tested for their ulcerogenic property. Based on these activity data, the compound 43 (in vitro COX‐2 activity—IC₅₀ = 0.4 μM, SI = 400, in vivo anti‐inflammatory activity—72% inhibition after 3 h, and 0.38%—Ulcer index) was emerged as most promising anti‐inflammatory agent with very low ulcerogenic action.