Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• metabolic enzymes. In addition, it has been shown to irreversibly inhibit isocitrate lyase 1 (ICL1) from Mycobacterium tuberculosis [40], and key metabolic protein for these pathogens [41]. Isocitrate lyases convert isocitrate to glyoxylate and succinate. Deprotonation of 3NP (pKa = 9.0) results in the

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• mycobactin from Mycobacterium tuberculosis [6]. 5′-O-Sulfamoyladenosine (AMS), a bioisosteric analog of an AMP intermediate, has been used as a non-hydrolysable scaffold for developing A-domain inhibitors. Moreover, 5′-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) and its derivatives show potent inhibitory

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• visible and near IR regions [11][12][13][14]. Similarly, simple quinoxaline-based heterocycles have shown their potential as photosensitizers to induce toxicity in a single cell green algae such as Chlamydomonas reinhardtii [15] and also displayed efficacy against Mycobacterium tuberculosis and other

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• -opioid receptor agonist and exhibits excellent antinociceptive activity [2]. Lactam C possesses potent antituberculosis activity and excellent selectivity to Mycobacterium tuberculosis strain H37Rv [3]. Araliopsine (D) was isolated from the fruits of Zanthoxylum simulans [4]. Benzofuran E is a potent and

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• cytotoxicity against leukemia cell line L-1210 (ED50 5 µg/mL) [39]. Aerothionin has been previously shown to exhibit antimycobacterial activity against monoresistant variants of Mycobacterium tuberculosis H37Rv, leading to further reported activity in various M. tuberculosis clinical isolates as well as non

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• IMPDH protein from Mycobacterium tuberculosis (PDB code 4ZQP) was performed. After 10 docking runs, a top-ranked solution was identified and definitively located at the same region occupied by IMP and inhibitor MAD1, ligands of the crystallographic structure in complex with IMPDH. As can be seen in

• representation) inside the IMPDH active site from Mycobacterium tuberculosis (cartoon representation – PDB code 4ZQP), with selected residues and interactions here also represented. Synthesis of 1-azido-3-nitrobenzene (c). Synthesis of the triazole-substituted triterpene derivatives 7 and 8. Antiviral activity

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• against Mycobacterium tuberculosis [128]. Of note is that in 2011, Astra Zeneca undertook some rather extensive strategic changes which led to an improvement of the drug discovery productivity and, possibly, to zoliflodacin (12) [129]. Another class of antibiotics deserving a place here should be the

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• raltegravir, the first HIV-integrase inhibitor approved by the FDA for the treatment of HIV infection, derived from 5,6-dihydroxypyrimidine-4-carboxamide and N-methyl-4-hydroxypyrimidinone-carboxamide [18] and hydroxypyrimidinone carboxamide derivative P01, a potent inhibitor of Mycobacterium tuberculosis

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• 32 µg/mL. Compounds 2 and 3 exhibited moderate activity against Mycobacterium tuberculosis H37Rv, with MIC values of 7.8 and 15.6 µg/mL, respectively. Plausible biosynthetic hypotheses toward the new compounds 1–5 were proposed. Keywords: Mycobacterium tuberculosis; Phenolic siderophores

• ][37], together with their antimicrobial activities against vancomycin-sensitive Enterococcus faecium VS144754 and Mycobacterium tuberculosis strain H37Rv. A plausible biosynthetic hypothesis is proposed towards the new compounds 1–5. Results and Discussion The preliminary LC–MS analysis of the

• concentration of 1–7 for vancomycin-sensitive Enterococcus faecium VS144754 and Mycobacterium tuberculosis H37Rv. Experimental procedure for antimicrobial assays. Supporting Information File 370: Additional analytical and experimental information. Acknowledgements We thank Russell Gray, Subha Arjuna, and Shan

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

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• 6-O-analogues are less common [61]. Azolylpurine derivatives are important due to their potential as drug candidates. They can be used as agonists and antagonists of adenosine receptors [58][64][65][66] and against Mycobacterium tuberculosis [60]. They also show useful fluorescent properties [11][67

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• activity against Mycobacterium tuberculosis and also as agonists and antagonists of adenosine receptors [18]. In 2013, we developed an efficient approach for the synthesis of ribo- and arabino-2,6-bistriazolylpurine nucleosides and showed that the triazolyl ring in the C6 position of purine acts as a good

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

• metabolite of marine Verrucosispora, effective against methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis [11][12]. The genus Kocuria, formerly categorized in the genus Micrococcus, is a Gram-positive unicellular coccus belonging to the family Micrococcaceae [13]. Members of

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

• albicans, Cryptococcus neoformans var. grubii, Mycobacterium tuberculosis) in vitro. Acute toxicity of BTA 3a in mice was determined to be higher than 1000 mg/kg, which means that BTA 3a can be considered as low toxic. Conclusion In conclusion, we developed two interchangeable approaches to enaminones

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• site of GlfT2, none of these compounds serve as efficient inhibitors of the enzymes involved in the mycobacterial galactan biosynthesis. Keywords: GlfT2; molecular modeling; mycobacterium tuberculosis; synthesis; transition state inhibitors; Introduction Tuberculosis (TB) is one of the most prevalent

• treatment in these cases is only 56% and 39%, respectively [1]. Clearly, the need for new and more efficient TB drugs is pressing. Among the novel therapeutic agents developed for TB, there are several compounds that target the cell wall of Mycobacterium tuberculosis, the causative agent of the disease [2

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• methyltransferase [27]. Entry of malonate as the acylate precursor into this pathway is proposed to yield 3 (4 in the original literature) [29]. Thus, 1 is very likely to be biosynthesized by the same mechanism followed by additional methylation on C3. Compound 1 is reportedly inhibitory to Mycobacterium

• tuberculosis H37Ra at IC90 6.8 μM while weakly cytotoxic to MRC-5 human lung-derived fibroblasts with GI50 84.7 μM [30]. It did not inhibit the production of nitric oxide in RAW 264.7 murine macrophage-like cells [31]. In our hands, 1 was inactive against any of the tested strains including Staphylococcus

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• , Germany 10.3762/bjoc.15.288 Abstract Arabinomannan (AM) polysaccharides are clinical biomarkers for Mycobacterium tuberculosis (MTB) infections due to their roles in the interaction with host cells and interference with macrophage activation. Collections of defined AM oligosaccharides can help to improve

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• or sulfonyl moiety with higher reactivity at the 2-position of the benzothiopyranone ring. In our continuing efforts to discover novel 2-amino-4H-benzothiopyran-4-ones with activity against Mycobacterium tuberculosis (Mtb) [5], we aim to develop an improved and efficient synthetic route by thoroughly

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• intracellular pathogens, such as Mycobacterium tuberculosis [10][11]. Carbohydrate-based probes provide one method to investigate parasitic mechanisms of immune suppression and evasion. The cell surface glycoconjugates on Leishmania have been implicated in the ability of the parasite to infect host cells, then

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• Abstract The importance of bacterial lectins for adhesion, pathogenicity, and biofilm formation is well established for many Gram-positive and Gram-negative bacteria. However, there is very little information available about lectins of the tuberculosis-causing bacterium, Mycobacterium tuberculosis (Mtb

• ). In this paper we review previous studies on the carbohydrate-binding characteristics of mycobacteria and related Mtb proteins, discussing their potential relevance to Mtb infection and pathogenesis. Keywords: adhesion; carbohydrates; fimbriae; lectins; Mycobacterium tuberculosis; pili; Introduction

• More than 135 years after the discovery of Mycobacterium tuberculosis (Mtb) by Robert Koch [1], tuberculosis (TB) is still one of the world’s deadliest communicable diseases [2]. TB is theoretically curable and preventable, especially since effective antibiotics have been available since the 1940s [3

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• forge the bacterial interactome [35]. However, despite the potential of these bacterial PPI maps, they have only been studied in detail in a few microorganisms including Escherichia coli (one of the best-studied model organisms in this field) [36][37][38][39], Mycobacterium tuberculosis [40

• colony formation evaluation of three of the previously mentioned hits (namely 24, 25 and 27) was assessed against a panel of bacterial strains that included Gram-positive microorganisms Listeria monocytogenes, Staphylococcus aureus, Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium avium

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• Mycobacterium tuberculosis [9][10]. The emergence of MDR-TB has led to structure–activity studies to enhance the antitubercular activity of phenothiazines leading to the identification of chlorpromazine analogue 1 (Figure 1) which demonstrates MIC values comparable to first-line TB drugs in vitro [11]. However

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• saccharides. The interest in hexofuranoses is based on the arabinogalactan-rich membrane of Mycobacterium tuberculosis and other harmful microorganisms which consists of primarily Araf and Galf subunits [44]. One key step in the biosynthesis of these hexofuranoses is the isomerization of uridine 5′-diphospho

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• . Teixobactin (17) was isolated from the β-protobacterium, Eleftheria terrae that belongs to a new genus. Teixobactin (17) demonstrated potent activity against the resistant Gram-positive bacteria, MRSA and vancomycin-resistant Enterococci (VRE), as well as other bacterial species including, Mycobacterium

• tuberculosis (Mtb) and Clostridium difficile. Remarkably, no teixobactin-resistant mutants of Staphylococcus aureus or M. tuberculosis could be detected after sub-lethal dosing of the compound over a 27 day period [43]. This lack of resistance development may possibly be attributable to the mechanism of action