Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• -Wittenberg, Kurt-Mothes-Str. 2, d-06120, Halle (Saale), Germany 10.3762/bjoc.17.154 Abstract Herein, a series of novel 1H-1,2,3-triazole and carboxylate derivatives of metronidazole (5a–i and 7a–e) were synthesized and evaluated for their antimicrobial activity in vitro. All the newly synthesized compounds

• metronidazole derivatives. The antimicrobial (antifungal and antibacterial) activity of the prepared compounds was studied. All compounds (except 2 and 3) showed a potent inhibition rate of fungal growth as compared to control and metronidazole. The synthetic compounds also showed higher bacterial growth

• inhibiting effects compared to the activity of the parent compound. Amongst the tested compounds 5b, 5c, 5e, 7b and 7e displayed excellent potent antimicrobial activity. The current study has demonstrated the usefulness of the 1H-1,2,3-triazole moiety in the metronidazole skeleton. Keywords: antimicrobial

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• absolute configuration was determined by combination of NOESY/ROESY and ECD analyses. Nomimicins B, C, and D showed antimicrobial activity against Gram-positive bacteria, Kocuria rhizophila and Bacillus subtilis, with MIC values in the range of 6.5 to 12.5 μg/mL. Nomimicins B and C also displayed

• antimicrobial activity against Kocuria rhizopila with a MIC value of 6.5 μg/mL and 1 and 2 were also active against Bacillus subtilis with a MIC value of 12.5 μg/mL. Compounds 1–3 were inactive against Staphylococcus aureus, Ralstonia solanacearum, Rhizobium radiobacter, and Candida albicans. In addition, 1 and

• tautomer are included in Supporting Information File 1. Biological assays Antimicrobial activity and cytotoxicity were evaluated according to the procedures previously described [29]. Structures of nomimicins A–D (4 and 1–3). COSY and key HMBC correlations for 1. Relative configuration of 1 determined by

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• , anthracene derivatives display useful biological activities; for instance, the anthraquinone derivatives 5 and 6 exert antimicrobial and anti-inflammatory activity, respectively (Figure 1) [15][16]. Despite some difficulties and limitations, a number of synthetic methods for preparing anthracene derivatives

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• tuning of the DP and fraction of acetylation (FA). Chitooligosaccharides (COS: β(1–4)-linked oligomers of GlcNAc and/or GlcN) have gained popularity due to their exceptional antimicrobial, antitumor, and immune modulatory activities [29][213][214][215][216][217]. Methods to obtain well-defined COS with

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• exhibit antimicrobial activity; however, they are also known to induce the growth and vigor of the host plant and to shape plant community structure [27][28][29][30][31]. Furthermore, volatiles released from endophytic fungi can also affect insect behavior. Daisy et al. isolated the endophytic fungus

• produced by endophytic fungi and are known to act as antimicrobial agents (Table 2) [63]. Sesquiterpenes make up the largest proportion of fungus-produced terpenoids [64] and in our study we also detected several sesquiterpenes, e.g., (E)-β-caryophyllene (1), β-chamigrene (4), aristolene (15), sativene (16

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• biological activities (Figure 1) [10]. Unsubstituted DIM (I), for example, exhibits antimicrobial [5], anticancer [11][12][13], and anti-inflammatory effects (Figure 1) [14]. There is preclinical evidence for activity against several types of cancer [15], and DIM has been clinically evaluated for the

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• , Bose Institute, P1/12 CIT Scheme VIIM, Kolkata-700 054, India 10.3762/bjoc.17.98 Abstract Double-headed nucleoside monomers have immense applications for studying secondary nucleic acid structures. They are also well-known as antimicrobial agents. This review article accounts for the synthetic

Analogs of the carotane antibiotic fulvoferruginin from submerged cultures of a Thai Marasmius sp.

• Birthe Sandargo,
• Leon Kaysan,
• Rémy B. Teponno,
• Christian Richter,
• Benjarong Thongbai,
• Frank Surup and
• Marc Stadler

Beilstein J. Org. Chem. 2021, 17, 1385–1391, doi:10.3762/bjoc.17.97

• fulvoferruginins A–F (1–6), aside from the known antifungal activity of fulvoferruginin (1), no other antimicrobial activities were observed (Table S2 in Supporting Information File 1). All metabolites were also tested against the murine fibroblast cell line L929 and the cervix carcinoma cell line KB3.1. While all

• in CD3OD are collected in Table 1 and copies of spectra are collected in Supporting Information File 1; HRMS–ESI (m/z): [M + H]+ calcd for C15H21O3+, 249.1490; found, 249.1480. Antimicrobial activity The minimum inhibitory concentrations (MIC) of metabolites 1–6 were assessed using a serial dilution

• assay in 96-well microtiter plates with YM6.3 media (10 g/L malt extract, 4 g/L glucose, 4 g/L yeast extract, pH 6.3) for filamentous fungi and yeasts, and with BD DifcoTM Mueller Hinton Broth for bacteria. The antimicrobial assays were performed as previously described [13]. Cytotoxicity assay The

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• rearrangement; cyclocondensation; heterocycles; thiazolidine-4-one; 1,2,4-triazine; Introduction The thiazolidin-4-one heterocyclic system is a well-known, accessible and, as a consequence, a widely used pharmacophore in the chemistry of biologically active compounds possessing antimicrobial [1

• well as related thiazolo[3,2-b]-1,2,4-triazines and thiazolo[2,3-c]-1,2,4-triazines possessing antimicrobial, antidepressant, anti-HIV, and anticancer activities [10][11][12][13][14][15]. Modifications of the position 5 of the thiazolidine cycle often lead to an enhancement of the pharmacological

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• transformed into β-lactam 60 in 90% yield by treatment with LDA in THF at −78 °C [90]. Compound 60 was converted after 9 steps in target batzelladines D 61 and 62 (Scheme 19). The authors explored also the antimicrobial activity of these compounds against a series of pathogens with starting promising results

• , and regulation of the immune response. Starting from α-alkoxy aldimines ent-126, the utility of this methodology was also demonstrated in the synthesis of alkaloid (+)-cassine (130), isolated from the leaves and twigs of Cassia excelsa, displaying antimicrobial activity. Methylmagnesium bromide was

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• also been employed in modern medicine because of its antimicrobial [3], antiprotozoal [4], antiviral [5], and anti-inflammatory [6] activity, and it is used in the treatment of tuberculosis [7], diarrhea [8], diabetes [9], cardiovascular diseases [10] or high cholesterol levels [11]. Most interestingly

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• . Observations revealed that the conventional refluxing method produced only 10% of the desired product and brought microwave assistance to light. The synthesized molecules showed good antimicrobial activity against Escherichia coli, Candida tropicalis, Staphylococcus aureus and Pseudomonas aeruginosa (Scheme 12

• (47) for prevention of influenza A and B. β-Lapachone (48) shows diverse biological activities like anticancer, antibacterial and anti-inflammatory activities [53]. Benzopyrans and naphthopyrans represent a class of fused pyrans that has been studied for antimicrobial effects (49 and 50, Figure 4) [54

• cancer cell lines along with good antimicrobial activity (Scheme 24). The proposed mechanism (Scheme 25) involved a Knoevenagel condensation between aldehyde 5 and malononitrile (51) to form arylidene intermediate A. Then A reacts with isocyanide 21 to produce intermediate B which coordinates with 1,10

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• class of heterocycles presents important biological properties, such as antiviral, anti-inflammatory, antimicrobial etc. and are considered as key building blocks in pharmaceutical industry [6][7][8][9]. Thus, they marked their presence as prominent scaffolds in many drug molecules such as tazobactam

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• MIC from <0.125 mg/L to 2 mg/L, and is comparable to avibactam against both E. coli strains with a MIC value of <0.125 mg/L. Keywords: amidine; antibacterial activity; β-lactamase inhibitors; diazabicyclooctane; synthesis; Introduction Survival stress posed by antimicrobial agents triggers multiple

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• analogs are an interesting group of pharmacologically active heterocycles [1][2], many of which possess, e.g., antimicrobial [3][4], antifungal [5], antidepressant [6][7], and antihistaminic [8][9][10] properties. Amino- and amidophthalazine derivatives have been examined, e.g., as inhibitors of PGE2

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• increasingly prominent in 19F NMR studies owing to their improved spectral properties. Among the first perfluorinated amino acids to be reported was perfluoro-tert-butylhomoserine (8), which was synthesized by Marsh and co-workers and incorporated into a variety of antimicrobial peptides, including MSI-78, for

• tactic in the battle against antimicrobial resistance. In addition to fluorinated metabolites that are produced de novo from fluoride ions, it is possible to modify other secondary metabolites to incorporate fluorine by including fluorinated precursors in the culture medium. 19F NMR has been applied to

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• biosynthesis [1][4], in vitro antimicrobial activity [4][5], and anticancer activity against human prostate cancer cell lines [6][7]. A recent study suggested that the close analogue (+)-11 of inthomycin C was found to exhibit proteasome inhibition activity [8]. The skeletal structures of inthomycins A–C (1–3

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• , Kgs. Lyngby, Denmark 10.3762/bjoc.16.248 Abstract Secondary metabolites provide Bacillus subtilis with increased competitiveness towards other microorganisms. In particular, nonribosomal peptides (NRPs) have an enormous antimicrobial potential by causing cell lysis, perforation of fungal membranes

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• -enantiomers with a ratio of 73:27, 4 is the pure (S)-enantiomer, and 5 is the (S)-enantiomer with 98% ee. The present study illustrates the diversity in the stereochemistry of anteiso branching in bacterial metabolites. Compounds 1−4 were moderately antimicrobial against Gram-positive bacteria and fungi, with

• the same as those for 1 (Table 1). The antimicrobial activity of 1–4 was tested against Gram-positive bacteria Kocuria rhizophila and Staphylococcus aureus, Gram-negative bacteria Escherichia coli and Rhizobium radiobacter, a yeast Candida albicans, and two fungi Glomerella cingulata and Trichophyton

• 13.5 min), nocarimidazole B (4, 8.0 mg, tR 17.3 min) from fraction 4, and bulbimidazole A (5, 3.2 mg, tR 11.2 min) from fraction 5. Bioassays The antimicrobial activity was evaluated in a similar manner as previously reported [22]. The cytotoxicity against P388 murine leukemia cells was examined

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• )-ones. A selective synthetic approach to 2-hydroxy-2H-1,4-benzothiazin-3(4H)-ones was developed via the solvent-switchable reaction of furan-2,3-diones with o-aminothiophenol. Preliminary biological assays (antimicrobial, acute toxicity) of the new compounds were carried out. Keywords: acylpyruvic acid

• use. Particularly, some enaminones I and II were found to show antioxidant [3], antimycotic [7][8], antimycobacterial [9][10], anti-Alzheimer’s disease (JNK3 inhibitors) [11], platelet aggregation inhibitory [12], antimicrobial [7] and analgesic [13] activities. Enaminones II were reported as

• , inducing its attack on the carbonyl group bearing a higher partially positive charge (for partial charges comparison, see Supporting Information File 1). As we were most interested in the biological activity of BTAs 3, preliminary antimicrobial and toxicity assays of these compounds were carried out

Styryl-based new organic chromophores bearing free amino and azomethine groups: synthesis, photophysical, NLO, and thermal properties

• Anka Utama Putra,
• Deniz Çakmaz,
• Nurgül Seferoğlu,
• Alberto Barsella and
• Zeynel Seferoğlu

Beilstein J. Org. Chem. 2020, 16, 2282–2296, doi:10.3762/bjoc.16.189

• azomethine group are one of the most widely used organic dyes because of their easy and cheap synthetic accessibility through various methodologies and suitable photophysical properties. In addition, they exhibit a broad range of biological activities such as antimicrobial, antifungal, antiviral, and

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• , anti-inflammatory, antimicrobial, anitubercular, psychotropic and anticancer [54][55][56][57][58][59][60]. The marketed cancer drug dasatinib [61] continues to prove its worth. In this work, it is shown that highly substituted oxazoles and aminothiazoles could be accessed directly from the reaction of

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• ], tau aggression [3], and heat shock protein 90 [4], in addition to their antimicrobial, cytotoxic, anticancer, and anti-inflammatory effects [5]. To date, over 400 azaphilones have been reported from various fungal strains, the majority of which have been produced by ascomycetes belonging to the

• elucidation, and antimicrobial activity evaluation are described. Results and Discussion Muyocopron laterale ECN279 was isolated from a healthy leaf of Canavalia lineata and identified by sequencing the D1/D2 26S rRNA gene and the internal transcript spacers (ITS) of ribosomal DNA [16]. In a similar manner as

• ,10R,11R) stereoisomer. Finally, since a number of azaphilones have been reported to exhibit antimicrobial activity [5][23], muyocopronones A (1) and B (2) were screened for their antibacterial activity against five strains of Gram-positive bacteria, namely Staphylococcus aureus (PAGU 273T

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• Thiazolopyrimidines, whose molecules includes both thiazole and pyrimidine rings, have a structural analogy with the antipsychotic drugs ritanserin and setoperone (Figure 1) [1][2][3]. To date, a wide spectrum of biological activity of thiazolopyrimidines has been determined: anticancer [4][5], antimicrobial [6][7