Synthesis,Characterization and In Vitro Antimicrobial Evaluation of Novel Pyrazolothiazol-4(5H)-one Derivatives

Antimicrobial screening of several novel pyrazolothiazol-4(5H)-one derivatives (3a-3j) has been performed. Reaction of aromatic aldehydes with aromatic ketones yielded starting chalcones (1a-1j) which have been subsequently reacted with thiosemicarbazide for obtaining N-thiocarbamoylpyrazole derivatives (2a-2j). These were further cyclized to pyrazolothiazol-4(5H)-one derivatives (3a-3j) in the presence of ethylbromoacetate. The structures of newly synthesized compounds were confirmed by FTIR and ¹H NMR and/or MS. The in vitro antimicrobial activity of these compounds was evaluated against Gram positive bacteria, Gram negative bacteria and fungi. Their minimum inhibitory concentration was determined by tube dilution method. The results showed that most of the compounds have promising antimicrobial activity as compared to standard drugs. Among the test compounds, 2-[5(4-chlorophenyl)-3-phenyl-4,5-dihydropyrazol-1-yl]-thiazol-4(5H)-one (3e) was found to show the most potent antimicrobial activity.     

Two new imidazole alkaloids from Leucetta chagosensis sponge

Chemical investigation of the sponge Leucetta chagosensis, has led to the isolation of two new imidazole alkaloids, methyldorimidazole (1), preclathridine B (2) along with the known compounds naamine E (3) and leucettamine C (4). The structures of the newly compounds (1 and 2) were elucidated by employing spectroscopic techniques (¹H NMR, MS and UV). The structures of the known compounds 3 and 4 were determined by comparison of their ¹H NMR and Mass spectroscopic data with published values.     

Mzabimycins A and B,novel intracellular angucycline antibiotics produced by Streptomyces sp. PAL114 in synthetic medium containing L-tryptophan

In our previous studies, the production of four bioactive molecules by Streptomyces sp. PAL114 in complex ISP2 broth medium has been described. Three of these molecules belong to the angucycline family. In this study, two novel antibiotics belonging to the same family were produced by strain PAL114 on M2 synthetic medium containing L-tryptophan as precursor. These antibiotics, named mzabimycins A and B, were intracellular and produced only in the presence of L-tryptophan. After four days of culturing PAL114 in the M2 medium, the bioactive compounds were extracted from mycelium with methanol and then analyzed by HPLC on reverse phase C18 column. Two active purplish blue fractions were purified. The chemical structures of these molecules were determined on the basis of spectroscopic and spectrometric analyses (¹H and ¹³C NMR, and mass spectra). They were identified to be novel angucycline derivative antibiotics. The pure molecules showed activity against some pathogenic Gram-positive bacteria which have multiple antibiotic resistance, such as Staphylococcus aureus MRSA 639c and Listeria monocytogenes ATCC 13932.     

Phytochemical and biological studies of Solanum schimperianum Hochst

Chemical reinvestigation of the aerial parts of Solanum schimperianum Hochst led to the isolation of ten compounds, lupeol (1), β-sitosterol (2), β-sitosterol glucoside (3), oleanolic acid (4), teferidin (5), teferin (6), ferutinin (7), 5-hydroxy-3,7,4′-trimethoxyflavone (8), retusin (9) and kaempferol-3-O-β-d-glucopyranoside (10). Compounds 5–7 were isolated for the first time from Solanaceae and compounds 1–4 and 8–9 for the first time from Solanum schimperianum. The structure elucidation of the isolated compounds was based on careful inspection of spectral data including 1D (¹H and ¹³C NMR), 2D (¹H–H COSY, HMQC and HMBC, ROESY), UV, MS and IR, in addition to, comparison with literatures. The antimicrobial activity of the extracts as well as the isolated compounds was tested. Only hexane extract showed activity against Bacillus subtilus and Staphylococcus aureus.     

Synthesis,Antimicrobial and cytotoxic activity of New Heterocyclic Hybrids Based on 2,5-Dimethylpyrrole and Pyrrole Scaffolds

A series of 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide analogs, some derived triazoles, azetidinones, thiazolidinones, and pyrroles have been synthesized in good yields and structures of these compounds were established by IR, ¹H NMR, ¹³C NMR, mass spectral, and elemental analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal, and antitubercular activity against Mycobacterium tuberculosis H₃₇ Rv strain by the broth dilution assay method. Twenty one of these compounds displayed good antimicrobial activity, with a MIC value of 1-4 μg/ml. Several compounds 4c, 8-10, 15b-15h, and 16b-16d exhibited good in vitro antitubercular activity with MIC value 1-2 μg/ml. Further, some title compounds were also assessed for their cytotoxic activity (IC₅₀) against mammalian Vero cell lines and A₅₄₉ (lung adenocarcinoma) cell lines using the MTT assay method. The results revealed that these compounds exhibit antitubercular activity at non-cytotoxic concentrations.     

Isolation and antihyperglycemic activity of flavonoid from flower petals of <Emphasis Type="Italic">Opuntia stricta</Emphasis>

The fresh flowers of Opuntia stricta were collected and extracted with 85% methanol under reflux. The concentrated extract was fractionated with Et₂O, EtOAc and petroleum ether. Rhamnetin 3-O-rutinoside was obtained from EtOAc fraction, as confirmed through ¹H and ¹³C NMR, ¹H-¹H NOESY, ¹H-¹³C HSQC, and mass spectra. The isolated flavonoid glycoside was investigated for its antihyperglycemic activity on alloxan-induced diabetic male albino rats.     

Synthesis, characterization, solvatochromic properties, and antimicrobial evaluation of 5-acetyl-2-thioxo-dihydro-pyrimidine-4,6-dione-based chalcones

A new series of chalcone analogs namely 5-(3-phenyl-acryloyl)-2-thioxo-dihydro-pyrimidine-4,6-dione have been synthesized from the key intermediate 5-acetyl-2-thioxo-dihydro-pyrimidine-4,6-dione 4′ with different aldehyde derivatives were performed to get the target compounds as thiobarbituric acid-based chalcones 5(a′–k′) and they were obtained in excellent yields. The newly synthesized compounds were characterized by spectral analysis (FT-IR, ¹H NMR, ¹³C NMR, and UV spectroscopy) and elemental analysis. The synthesized compounds were evaluated for their antimicrobial activity against five bacterial strains (S. aureus, S. pyogenes, E. coli, K. pneumoniae, and P. aeruginosa) and four fungal strains (C. albicans, A. clavatus, T. rubrum, and Penicillium wild strain). Among the screened compounds, 5e′ and f′ showed comparable activity (minimum inhibitory concentration = 500 μg/mL) nearly to that of standard antibiotics griseofulvin.     

Synthesis, stereochemistry, and antimicrobial evaluation of t(3)-isopropyl-r(2), c(6)-di-2′-furanylpiperidin- 4-one and its derivatives

In a wide search program for new and efficient antimicrobial agents, a series of t(3)-isopropyl-r(2),r(6)-di-2′-furanylpiperidin-4-one 1 and its derivatives 2–7 were synthesized; characterized by IR, ¹H NMR, ¹H-¹H COSY, ¹³C NMR, and mass and elemental analysis; and their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa and antifungal activity against Candida-6, Candida albicans, Aspergillus niger, Candida-51 and Aspergillus flavus was evaluated. Compound 6 exerted potent in vitro antibacterial activity against B. subtilis while compound 6 exhibited in vitro antifungal activity against Candida-6.     

A New Flavonoid C-Glycoside from Celtis australis L. and Celtis occidentalis L. Leaves and Potential Antioxidant and Cytotoxic Activities

A major development over the past two decades has been the realization that free radical induced lipid peroxidation and DNA damage are associated with major health problems, e.g. cancer and ageing. Plant-derived antioxidants are increasingly found beneficial in protecting against these diseases. Celtis australis L. and Celtis occidentalis L. are two plants that have a variety of uses in folk medicine but have not been evaluated before for their antioxidant and cytotoxic properties. Therefore, the extracts of both plants’ leaves were investigated for these activities, as well as isolation of the bioactive compounds responsible for the activities. Molecular structures of the compounds were elucidated by UV, HRESIMS, 1D (¹H and ¹³C) and 2D (¹H-¹³C HSQC and ¹H-¹³C HMBC) NMR analyses. The ethanolic and aqueous extracts, n-butanol fractions and the isolated major compound were tested for their antioxidant activity using DPPH radical scavenging assay, xanthine oxidase-induced generation of superoxide radical and lipid peroxidation assay by thiobarbituric acid-reactive substances (TBARS) method using rat tissue homogenates. Cytotoxic activities were studied using standard MTT assay. A novel flavonoid C-triglycoside, 4‴-α-rhamnopyranosyl-2″-O-β-d-galactopyranosylvitexin, was isolated from both plants’ leaves, together with seven known flavonoids. The n-butanol fractions and the major compound 2″-O-β-galactopyranosylvitexin showed significant antioxidant activities, more pronounced than the tested standards BHT and dl-α-tocopherol in most tests. All extracts showed variable cytotoxic activities. This study provides strong evidence for the antioxidant and cytotoxic activities of the extracts of Celtis australis L. and Celtis occidentalis L. leaves, which were attributed to the polar n-butanol fractions and the major isolated flavonoid 2″-galactosylvitexin.     

A new streptothricin family antibiotic producingStreptomyces spp. SNUS 8810-111; Characterization of the producing organisms,fermentation, isolation,and structure elucidation of antibioitics

A new streptothricin family antibiotic producingStreptomyces spp. SNUS 8810-111 was isolated from a soil sample. Study of its morphological and physiological characters indicated that the antibiotic producing organism was aStreptomyces spp. Taxonomical studies suggested that the organism might belong to the genusStreptomyces gougeroti. The organism produced antibiotics most in calcium carbonate-tryptic soy broth. The active principles were recovered from the broth with a cation exchange resin and eluted from the resin with HCl. Cellulose column chromatography gave two active principles.¹H-¹H Homo-COSY study on the first compound revealed four structural components. Total hydrolysis of the antibiotic with HCl allowed isolation of β-lysine. From these data the antibiotic was found to be streptothricin D. The other compound showed one additional signal in the¹H NMR and the¹³C NMR spectra. The signal was from a methyl group attached to a nitrogen atom. Comparison of the NMR signals with those of streptothricin D suggested that the compound wasN-methyl-streptothricin D which was a new compound in the family of streptothricin antibiotics.     

“In water” diastereoselective [3+2] cycloaddition reaction: Clean and green synthesis of pyrrolo[1,2-a]quinolines

A simple, room temperature, clean and green process for [3 + 2] cycloaddition reaction of quinoline-derived heteroaromatic N-ylide and N-aryl maleimides in the aqueous medium has been developed. The reaction afforded tetracyclic pyrrolo[1,2-a]quinolines with four stereogenic centres in excellent yield and high diastereoselectivity. The synthesized compounds were fully characterized with spectroscopic techniques (IR, ¹H NMR, ¹³C NMR). Single crystal x-ray diffraction analysis (SCXRD) confirmed the relative stereochemistry of the final compound. The synthesized compounds exhibit the antioxidant properties which were determined by ferric reducing antioxidant power assay (FRAP).     

Efficient identification of fungal antimicrobial principles by tandem MS and NMR database

The continuous re-isolation of the known and non-applicable compounds that is time-consuming and wasting resources is still a critical problem in the discovery of bioactive entities from natural resources. To efficiently address the problem, high performance liquid chromatography-diode array detector-microfractionation (HPLC-DAD-microfractionation) guided by disk agar diffusion assay was developed, and the active compounds were further identified using the tandem mass spectrometry (MS/MS)-based molecular networking. Of 150 fungal strains screened, the methanolic extracts of Phoma herbarum PPM7487, Cryptosporiopsis ericae PPM7405, and Albifimbria verrucaria PPM945 exhibited potent antimicrobial activity against Candida albicans SC5314 and Cryptococcus neoformans H99 in the preliminary agar diffusion assay. The concept of OSMAC (one strain many compounds) was employed in the fungal cultures in order to enrich the diversity of the 2^nd metabolites in this study. HPLC coupled with off-line bioactivity-directed profiling of the extracts enabled a precise localization of the compounds responsible for the conspicuous antimicrobial activity. The purified active compounds were identified based mainly on MS/MS database, and further supported by ¹³C nuclear magnetic resonance (NMR) spectral data compared to the literatures. In addition to nineteen known compounds, a new trichothecene derivative 1, namely trichoverrin D, was isolated and identified through this protocol. The antifungal activities of all the pure isolates were evaluated, and the structure activity relationships were also inferred. This report has demonstrated the combination of HPLC microfractination and MS/MS coupled by NMR spectral dereplication for speeding up the antimicrobial natural products discovery process.     

Design, synthesis, and in vitro antimicrobial activities of novel azetidinyl-3-quinazolin-4-one hybrids

A series of 2-[(4′-oxo-3′-chloro-2′-phenylazetidin-1′-ylamino)-methyl]-3-[N-isonicotinamide-yl]-quinazolin-4-one hybrids were synthesized starting from anthranilic acid in basic media using chloroacetyl chloride and benzene as solvent. The structure of the synthesized compounds has been evaluated on the basis of their elemental (C, H, and N) and spectral analysis (IR, ¹H NMR, and ¹³C NMR spectrometry). In vitro antimicrobial evaluation of the synthesized compounds revealed that they posses promising antimicrobial activity against some gram-positive and gram-negative bacteria. Furthermore, compounds 7d and 7f exhibited potent antitubercular activity.     

Synthesis, characterization, and pharmacological evaluation of 1-[2-(6-nitro-4-oxo-2-phenyl-4H-quinazolin-3-yl)-ethyl]-3-phenyl ureas

In the present communication, a series based on 1-[2-(6-nitro-4-oxo-2-phenyl-4H-quinazolin-3-yl)-ethyl]-3-phenyl-urea have been synthesized by an efficient synthetic protocol. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR spectroscopy, ESI Mass spectrometry, and elemental analysis. The antibacterial and antifungal activity of the compounds were studied against selected strains (Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 11774, and Candida albicans ATCC 66027) by using Kirby Bauer disk diffusion technique and broth dilution technique. All the synthesized compounds showed good antifungal potency against strain C. albicans.     

Controlled Production of Zearalenone-Glucopyranoside Standards with Cunninghamella Strains Using Sulphate-Depleted Media

In recent years, conjugated mycotoxins have gained increasing interest in food safety, as their hydrolysis in human and animal intestines leads to an increase in toxicity. For the production of zearalenone (ZEN) glycosides reference standards, we applied Cunninghamella elegans and Cunninghamella echinulata fungal strains. A sulphate-depleted medium was designed for the preferred production of ZEN glycosides. Both Cunninghamella strains were able to produce zearalenone-14-β-D-glucopyranoside (Z14G), zearalenone-16-β-D-glucopyranoside (Z16G) and zearalenone-14-sulphate (Z14S). In a rich medium, Cunninghamella elegans preferably produced Z14S, while Cunninghamella echinulata preferably produced Z14G. In the sulphate-depleted medium a dramatic change was observed for Cunninghamella elegans, showing preferred production of Z14G and Z16G. From 2 mg of ZEN in sulphate-depleted medium, 1.94 mg of Z14G and 0.45 mg of Z16G were produced. Following preparative Liquid Chromatography-Mass Spectrometry (LC-MS) purification, both fractions were submitted to ¹H and ¹³C NMR and High-Resolution Mass Spectrometry (HRMS). These analyses confirmed that the purified fractions were indeed Z14G and Z16G. In conclusion, the presented research shows that a single Cunninghamella strain can be an effective and efficient tool for the controlled biotransformation of ZEN glycosides and other ZEN metabolites. Additionally, the biotransformation method was extended to zearalanone, β-zearalenol and other mycotoxins.     

Several chromones from the stems of Polygonum aubertii Henry

Two new 2-alkylchromanones, 2-tricosyl-2,5,7-trihydroxy-chromanone (6) and 2-pentacosyl-2,5,7-trihydroxy-chromanone (7), together with five known 2-alkylated chromones and chromanones (1–5), were isolated from the stems of Polygonum aubertii Henry. The structures of these compounds were established by spectroscopic methods including extensive 1D, 2D NMR (¹H-¹H COSY, HSQC, and HMBC), and HR-ESI-MS techniques. In addition, a plausible biosynthetic pathway for these compounds is described.     

Coumarins Isolated from the Roots of Seseli resinosum. in Turkey

Abstract

Seseli resinosum. Freyn et Sint. (Umbelliferae) is a perennial herb that grows in the northern region of Anatolia, Turkey. The n.-hexane extract obtained from the roots of S. resinosum. was investigated for the presence of coumarins. Three angular-type pyranocoumarins and two linear-type furocoumarins were isolated from the roots. The compounds were identified as (+)-samidin [(3′S., 4′S.)-3′-senecioyloxy-4′-acetoxy-3′, 4′-dihydroseselin] (1), (?)-anomalin [(3′R., 4′R.)-3′, 4′-diangeloyloxy-3′, 4′-dihydroseselin] (2), calipteryxin (3′R., 4′R.)-3′-angeloyloxy-4′-senecioyloxy-3′, 4′-dihydroseselin (3), isoimperatorin (4), and deltoin (5). The structures were determined using spectroscopic methods (¹H NMR, ¹³C NMR, ¹H-¹H COSY, ¹H-¹³C COSY, HMBC, MS), physical methods (melting point and optical rotation), and chemical correlations with known compounds that have been described in the literature. The chemotaxonomic significance of these isolated coumarins is discussed in the genus Seseli. L.     

Synthesis and evaluation of novel benzimidazole derivatives as antimicrobial agents

Benzimidazole analogs bearing electron-withdrawing as well as electron-donating substituent were synthesized to achieve bioactive molecules with significant antimicrobial property. The desired compounds were prepared by multi-step synthesis process. The formation of intermediates and their corresponding derivatives (III _1–13 ) was confirmed by spectral characterization such as ¹H NMR, ¹³C NMR, mass spectra, IR, and elemental analysis. The compounds were screened for their antimicrobial properties against a broad panel of Gram-positive and Gram-negative bacteria as well as fungi. From the SAR study data, it was observed that the derivatives with electron-withdrawing functional groups were more bioactive than that with electron-donating functional groups.     

Bioactive Terpenoids and Flavonoids from Daucus littoralis Smith subsp. hyrcanicus Rech.f,an Endemic Species of Iran

Background

Daucus littoralis Smith subsp. hyrcanicus Rech.f. (Apiaceae) is an endemic species in northern parts of Iran where it is commonly named Caspian carrot. The fruits have been used as condiment.

Methods

In a series of in vitro assays, antioxidant (DPPH and FRAP assays), cytotoxic and antimicrobial activities of different extracts of roots and fruits were evaluated for the first time. The separation and purification of the compounds were carried out on the most potent extracts using various chromatographic methods and identified by spectroscopic data (¹H and ¹³C NMR).

Results

The results showed that among the extracts only fruit methanol extract (FME) has significant antioxidant activity (IC₅₀ = 145.93 μg.ml^-1 in DPPH assay and 358 ± 0.02 mmol FeII/g dry extract in FRAP assay). The radical scavenging activity of FME at 400 μg.ml^-1 was comparable with α-tocopherol (40 μg.ml^-1) and with BHA (100 μg.ml^-1) (p > 0.05). FME did not show any toxicity against cancerous and normal cell lines. Fruit ethyl acetate extract (FEE) had cytotoxic activity against breast carcinoma and hepatocellular carcinoma cells (IC₅₀ 168.4 and 185 μg.ml^-1, respectively), while it did not possess antioxidant activity in comparison with α-tocopherol and BHA as standard compounds. Ethyl acetate and methanol extract of fruits showed antimicrobial activity against Staphylococcus aureus (MIC: 3.75 mg.ml^-1) and Candida albicans (MIC: 15.6 and 7.8 mg.ml^-1, respectively). Four terpenoids were isolated form FEE including: β-sitosterol (1), stigmasterol (2), caryophyllene oxide (3), β-amyrin (4). Also, three flavonoids namely quercetin 3-O-β-glucoside (5), quercetin 3-O-β-galactoside (6) and luteolin (7) were isolated from FME.

Conclusion

This study showed that FEE and FME of D. littoralis Smith subsp. hyrcanicus Rech.f. had the highest biological activities which may be correlated with in vitro cytotoxic, antimicrobial and antioxidant activities of terpenoids and flavonoids components of the extracts.     

Synthesis and biological evaluation of novel quinolin-2(1H)-one derivatives as potential antimicrobial agents

A series of novel quinolin-2(1H)-one derivatives were synthesized and characterized by IR, ¹H NMR, ¹³C NMR, and MS spectral data. All the new compounds were screened for their antimicrobial activities against six trains of bacteria and five fungi in vitro by twofold serial dilution technique. The bioactive assay showed that most of the compounds exhibited moderate to good antimicrobial activities in comparison with the streptomycin, especially, compound 6a, the fluoro-substituted aromatic amide derivative, showed good antibacterial activities against B.proteus and P.aeruginosa with minimal inhibitory concentration value of 32 and 16 μg/ml, respectively.