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

• development of the drugs against tuberculosis. Despite that the studied structures do not contain the galacto configuration on the furanose ring, the studied compounds mimic the TS structure of the GlfT2 catalytic reaction. The TS structure mimetics are stable compounds designed to mimic the unstable TS

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

• 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

• million people in 2017. Additionally, more than 10 million new tuberculosis (TB) cases were reported, with multidrug-resistant TB accounting for almost 10% of the registered cases [1]. The development of novel therapeutic agents and more efficient strategies to detect MTB infections at an early stage is

• essential, as an early diagnosis would help to prevent most deaths from tuberculosis [1]. AMs, one of the main components of the mycobacterial cell wall [2], are composed of α-(1,5)-, α-(1,3)- and β-(1,2)-arabinoses as well as α-(1,6)- and α-(1,2)-mannosides [3][4][5]. AMs are potential clinical biomarkers

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• failure), zolpidem (for treatment of insomnia), zolimidine (antiulcer drug), alpidem and saripidem (anxiolytic agents) and some are under development, like GSK812397 (for the treatment of HIV), ND-09759 and Q203 (for tuberculosis) (Figure 1) [6][7][8][9][10]. The synthesis of imidazopyridines (IPs) is

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

• Katharina Kolbe Sri Kumar Veleti Norbert Reiling Thisbe K. Lindhorst Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, 33 North Drive, Bethesda, 20892, MD, United States Microbial Interface Biology, Research

• 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

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

• properties and the availability of other drugs such as rifampicin, the optimization programme was abandoned [70]. Recently, the interest in neglected antibiotics with anti-tuberculosis potential resurged and led to further optimization and development studies around the griselimycin structure (21, Figure 5

• ) [71]. Müller et al. discovered that griselimycin and its metabolically more stable analogues (methyl-griselimycin, MGM, 22 and cyclohexyl-griselimycin, CGM, 23) were active against M. tuberculosis in the low micromolar range with MICs of 1, 0.6 and 0.06 μg/mL, respectively. To characterize the target

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

• Abed Tarapdar James K. S. Norris Oliver Sampson Galina Mukamolova James T. Hodgkinson Leicester Institute of Structural and Chemical Biology, and Department of Chemistry, University of Leicester, George Porter Building, University Road, Leicester, LE1 7RH, UK Leicester Tuberculosis Research Group

• conjugates can demonstrate enhanced uptake and internalisation to the bacterial cell resulting in significantly reduced MIC values and extended spectrum of activity. Phenothiazines are a class of small molecules that have been identified as a potential treatment for multidrug resistant tuberculosis and

• 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

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• become a major concern of governments and health workers due to the economic and health burden it has brought. HCV has been found to be the main cause of liver associated deaths globally putting it in the same league of HIV and tuberculosis in terms of worldwide health challenges [1]. Approximately 71

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• order to probe their antifungal and antimycobacterial activity; several of these novel conjugates showed promising activity against the fungus C. neoformans (MIC80s ranging from 0.25–4 μg/mL) and the mycobacterium M. tuberculosis (MIC99s 3.1 μM) [62]. Since the last few decades, a plethora of synthetic

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• using 4-aminosalicylic acid and piracetam. 4-Aminosalicylic acid is an antibiotic that has been used in the treatment of tuberculosis, inflammatory bowel diseases, namely distal ulcerative colitis [125][126] and Crohn’s disease [127], while piracetam is a nootropic drug used to improve cognitive

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• common mycobacterial infection after tuberculosis and leprosy [1][2][3]. At its outset Buruli ulcer usually occurs as painless subcutaneous swellings in the form of nodules, papules, plagues or diffuse edema [4]. Due to their inconspicuous appearance, early disease stages might be confused with insect

• Republic of the Congo), the pathogen is also endemic in South America, the Western Pacific region (incl. Australia) and Asia (e.g., China and Japan). In certain highly endemic regions like the Zou department in southern Benin, the prevalence of Buruli ulcer can even exceed that of tuberculosis or leprosy

• all patients that distinctly differed from tuberculosis. However, the germ gave the typical acid-fast stain common to all mycobacteria. As reported by Fenner et al., MacCallum later suggested the name Mycobacterium ulcerans [17]. Initial attempts to cultivate the bacterium failed until it was realized

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

• 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

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• , which is also glycosylated in 5'-position with an aminoribose unit, and they contain a fatty acid moiety as well. Caprazamycins also display noteworthy antimicrobial activity against M. tuberculosis as well as most Gram-positive bacteria (Table 1) [46][48]. All aforementioned nucleoside antibiotics

• activity against Gram-positive bacteria, Pseudomonas and M. tuberculosis [48]. The related liposidomycins display good activity against M. phlei, while they are not active against a range of other bacteria [45]. Mode of action To develop an effective antibiotic one needs to choose a target that is

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• , the enzymatic products of which exhibited high sequence similarity to proteins that are responsible for the biosynthesis of tuberculosinol and isotuberculosinol in Mycobacterium tuberculosis [128]. Following in vitro studies of the two Herpetosiphon enzymes as well as a reconstitution of the entire

Mycothiol synthesis by an anomerization reaction through endocyclic cleavage

• Shino Manabe and
• Yukishige Ito

Beilstein J. Org. Chem. 2016, 12, 328–333, doi:10.3762/bjoc.12.35

• cell from toxic chemicals. The inhibition of the mycothiol biosynthesis is considered as a treatment for tuberculosis. Mycothiol contains an α-aminoglycoside, which is difficult to prepare stereoselectively by a conventional glycosylation reaction. In this study, mycothiol was synthesized by an

• anomerization reaction from an easily prepared β-aminoglycoside through endocyclic cleavage. Keywords: anomerization; aminoglycoside; endocyclic cleavage reaction; inositol; mycothiol; Introduction Tuberculosis is an infectious disease and has had a high death rate over the past few decades [1][2][3][4]. The

• occurrence of multiple-drug-resistant (MDR), extensive-drug-resistant (EDR), and totally drug-resistant (TDR) pathogens has increased the need for new drug candidates for treating tuberculosis. Mycothiol (MSH) 1 is the main low-molecular-weight thiol found in most actinomycetes, including Mycobacteria and

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• significant antituberculosis (TB) activity (MIC of 0.35 µM) against Mycobacterium tuberculosis H37Rv [70]. The 6H-pyrido[2,3,4-kl]acridin-6-one motif has been used as a core to develop other anti-TB compounds. In this way, the same activity has been observed with 4-(ethylthio)-6H-pyrido[2,3,4-kl]acridin-6-one

New depsidones and isoindolinones from the mangrove endophytic fungus Meyerozyma guilliermondii (HZ-Y₂) isolated from the South China Sea

• Senhua Chen,
• Zhaoming Liu,
• Yayue Liu,
• Yongjun Lu,
• Lei He and
• Zhigang She

Beilstein J. Org. Chem. 2015, 11, 1187–1193, doi:10.3762/bjoc.11.133

• 8 and 10 inhibited α-glucosidase with moderate to weak activities (Table 3). All isolated compounds were also evaluated for their inhibitory activity against Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB), of which were inactive (IC50 > 200 μM). Experimental General experimental

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• recognized as active agents against tuberculosis and malaria [3][7], cardiovascular diseases [3], and cancer [4]. Cinnamates show depigmenting [4], antidiabetic, antihyperglycemic, anticholesterolemic, anti-inflammatory, hepatoprotective, CNS depressant, anxiolytic, and cytotoxic activity [7]. Cinnamate

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• inhibitors of acetylcholine esterase and butyrylcholine esterase [5], compounds of this series exhibit as well anti-tuberculosis [6] and anti-inflammatory activities [7]. Another promising area for the use of thieno[2,3-b]indoles, as electron-rich heteroaromatics, is the design of photo- and electroactive

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• for the enzymes of Mycobacterium tuberculosis, in particular a deacetylase implicated in the biosynthesis of mycothiol, is under way and the results will be reported in the future. Single X-ray crystal structure of hemithioacetal 3a. (i) CAN, wet silica, KBr, CH2Cl2/CH3CN (1:1), rt, 30 min; (ii) a

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• (Mycobacterium tuberculosis) [17] (Table 2). Promising antiplasmodial activity was seen with the spirocyclic compound 12 (IC50 2.65 µg/mL, 6.25 µM) and the related indoloazepinoindol-17-one 17 in which the allylic substituents are effectively merged (minus the ether oxygen) and embedded in the 7-membered ring