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

• activities against the A-domain of MbtA, a component of mycobactin synthetase and antimicrobial activities against M. tuberculosis [7]. In addition, aminoacyl (AA)-AMS has been designed to inhibit the amino acid-activating A-domains in NRPSs and has been found to be a tight-binding inhibitor (Figure 2b) [8

• introduced a pegylated biotin linker at the 2′-OH group of ʟ-Phe-AMS and confirmed that the probe retains the binding activities toward the A-domain of GrsA, a gramicidin S synthetase. Aldrich et al. developed a Sal-AMS-based activity-based probe (ABP) to profile MbtA in M. tuberculosis [12]. In contrast, we

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

• -tuberculosis mycobacteria [42]; while antitumour [43] and antifouling [44] activities have also been published. Conclusion In summary, we report here the UHPLC–MS profiling of 39 Verongida sponge extracts from NatureBank, which led to large-scale extraction and mass-directed isolation studies on an Ianthella

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

• new drugs to treat tuberculosis is also of interest. The starting point was probably CGI-17341 (20), a mutagenic compound reported by Ciba-Geigy in 1989 for its effect on mycobacteria [150]. And this substance owes its origin to the many nitroimidazole derivatives known for their anti-infective

• result of extensive structure–activity relationship studies, especially to avoid mutagenic effects, undertaken by PathoGenesis/Novartis. Similarly, delamanid (19), first reported [153][154] in 2006 and approved in 2014 for its use against tuberculosis, was the fruit of extensive research made by Otsuka

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

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• spectroscopic techniques. The biological properties of the freshly prepared compounds were screened against S. aureus, B. subtilis, A. hydrophila, E. coli, and A. baumannii bacteria and antituberculosis activity against M. tuberculosis H37Rv strains. Also, the antifungal activity was studied against C. albicans

• organometallic compounds were screened for their antibacterial activity against a range of Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Aeromonas hydrophila, Escherichia coli, Acinetobacter baumannii) bacteria and antimycobacterial activity against M. tuberculosis H37Rv strains

• tested against the M. tuberculosis H37Rv strain with 3.90 μg/mL. It seems that the presence of the indole ring has enhanced the activity of complex L3-Ni when comparing with other Ni complexes such as L1-Ni and L2-Ni. Antifungal activity The screened complexes showed antifungal activity, in the range of

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• [44][45]. In particular, they have been widely explored for the treatment of Alzheimer's disease [46][47][48][49][50][51], human cancer [52][53], and tuberculosis [54] (Figure 1). Taking into consideration the significant medicinal potential of tetrahydroacridines and the lack of knowledge concerning

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• against cancer [6][7], tuberculosis [8], Gram-positive bacteria [9], and they are used in treatment of epilepsy [10] and Alzheimer disease [11][12][13]. The synthesis of compounds of the 1,2,4-oxadiazole series is an actual task in organic and medicinal chemistry (see selected reviews on this topic [14

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

• -sensitive E. faecium VS144756, and M. tuberculosis H37Rv (see Table S8 in Supporting Information File 1). Compound 4 was the most potent against Vancomycin-sensitive E. faecium VS144754, with a MIC value in a range of 8–16 µg/mL, followed by compounds 3 and 5, which showed MIC values of 16 and 32 µg/mL

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

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• plant constituents and display a wide range of pharmacological and biological activities, such as anticancer [1], antibacterial [2], and antifungal [3]. Moreover, coumarin derivatives have shown activity against neglected diseases as leishmaniasis [4], tuberculosis [5][6] and Chagas’ disease [7

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

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

• [65]. Accordingly, the activity of these derivatives in the treatment of tuberculosis [7], diarrhea [8], diabetes [9], cardiovascular diseases [10] or high cholesterol levels [11] is worth to be tested, because the parent berberine is already employed as drug for these diseases. In summary, a new

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

• 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