Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• of the Czech Academy of Sciences, Flemingovo náměstí 542/2, 166 10 Prague, Czech Republic 10.3762/bjoc.20.91 Abstract The RNA-dependent RNA polymerase (RdRp) represents a prominent target in the discovery and development of new antivirotics against RNA viruses, inhibiting the replication process

• directly act as a viral messenger RNA and encodes essential enzymes for replication [3]. Inhibiting these nonstructural proteins that are part of the replication complex has already shown great success in antiviral therapy [4][5][6][7]. The viral RNA-dependent RNA polymerase (RdRp) is encoded in all RNA

• viruses and plays a crucial role in viral RNA replication. In the proteome of SARS-CoV-2, the catalytic subunit nsp12, expressed together with the cofactors nsp7 and nsp8, constitutes the RdRp [8]. RdRp is usually targeted by nucleotide analogue inhibitors (NAIs) [9]. This class of antivirals can inhibit

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• ortho- and meta-benzenes was for a long time low [14], but recent years have seen a surge in interest in developing such systems. In these cases, replication of the 60° and 120° bond angles of ortho- and meta-benzenes is a key challenge. This review will summarise the progress made so far towards the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• antiviral properties. BIMs function as selective antibacterial agents against several virulent Escherichia coli (E. coli) strains, which can cause many gut and urinary tract infections. They act by damaging DNA molecules and inhibiting their replication in bacteria, while also targeting the proteins that

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• a change of the DNA structure or occupy binding sites of essential enzymes, which in turn may influence or even inhibit important biochemical processes, for example DNA replication or transcription [1][2]. As a result, the development of DNA-targeting drugs still involves the design of suitable DNA

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• avicennae [18]. Inhibition of hepatitis C virus replication by 2-nonyl-4-quinolone, isolated from Ruta angustifolia leaves, has also been reported [19]. Another significant group of natural 4-quinolones are those of microbial origin. The function of these compounds in the microbial world is a matter of

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

• the purealidin bromotyrosine structure class, however, quorum sensing inhibition and antifouling activities against several strains of bacteria and microalgae appears in the literature [33][34], while HIV-1 replication inhibition and anti-Leishmania and Plasmodium activity has also been recorded [35

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

• synthesis of guanosine triphosphate, which leads to a GTP depletion, thus, it prevents the replication of many RNA and DNA viruses [10]. Despite this, its efficacy has been controversial, as its use can cause hemolytic anemia, which is the leading cause for treatment being discontinued in 36% of real-life

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

• ]. In this case, as depicted in Figure 7, from the hit 37 found, the ensuing structure–activity relationship studies of 2000 analogues led to JNJ-A07 (38) which has between nanomolar and picomolar level of effects against dengue virus replication in cell lines and as well as an in vivo effect on a mice

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• cause several damages to its components, such as carbohydrates, lipids, membrane components, and enzymes that are critical for DNA replication [9][10][11][12]. Most synthetic strategies toward naphthoquinones with potential biological activity start from natural and synthetic naphthoquinones, inserting

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• . These molecules play a significant role in replication, transmission, and transcription of genetic material in life forms [1]. Structural analogues similar to the naturally occurring 2'-deoxynucleosides and ribonucleosides, the DNA and RNA building blocks, respectively, are expected to mimic their

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• group is another powerful organic function present for example in zidovudine, a worldwide known anti-HIV drug, but also in its derivatives (61 and 62) (Scheme 22A), which can present 10-times higher activities against HIV replication [143]. In 2020 the same group reported the use of a manganese catalyst

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

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• , replication, splicing and other fundamental processes in biological information transfer. More specifically, they can affect chemical and thermodynamic stability, folding, secondary and tertiary structure, activity and interactions between nucleic acids, proteins and receptors. Particularly, as far as

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• platforms compatible with antiretroviral drugs. Specifically, a productive CNS delivery of such compounds is expected to reduce HIV-1-associated neurological disorders as well as to reduce HIV-1 replication at this sanctuary site [13][50][51]. We investigated the use of T7 and Tat peptides and evaluated the

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

• important role in key biological processes such as gene expression and regulation [94][95], telomere length maintenance [96][97][98], transcription and DNA replication [99][100]. Investigation of the specific G-quadruplex structures associated with these biological events is therefore essential to

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• and on the acyclovir-resistant strains), as they interfered with late steps in the viral replication cycle [25]. An interesting feature of the Ugi reactions shown with ketosteroids having additional carboxylic and aldehyde groups (see Scheme 1 and Figure 2B) is the lack of side reaction at the ketone

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• cause nephrotoxicity [7]. The mode of action of adefovir has been widely studied and involves the inhibition of viral replication by the termination of DNA synthesis [8][9][10]. Although adefovir was described in 1986 for the first time by Holý, De Clercq and co-workers, it is still actively employed in

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• , suggesting the possibility of its use as an anticancer compound. Besides, inhibition of sphingolipid biosynthesis using HPA-12 has also been reported to inhibit hepatitis C virus replication substantially [4]. In another study, the CERT knockdown disrupted the normal oxidative stress response in Drosophila

Selective ring-opening metathesis polymerization (ROMP) of cyclobutenes. Unsymmetrical ladderphane containing polycyclobutene and polynorbornene strands

• Yuan-Zhen Ke,
• Shou-Ling Huang,
• Guoqiao Lai and
• Tien-Yau Luh

Beilstein J. Org. Chem. 2019, 15, 44–51, doi:10.3762/bjoc.15.4

• ]. Unsymmetrical polynorbornene-based ladderphane is obtained by a replication protocol from a single stranded polynorbornene [19][20]. Alternatively, sequential polymerization of a monomer containing a norbornene moiety and other polymerizable group furnishes an unsymmetrical ladderphane having two structurally

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

• target cells of Mtb bacteria are primarily alveolar macrophages, which internalize the pathogen through phagocytosis [6]. These innate immune cells initiate a number of responses to limit bacterial replication and spread with the ultimate goal of eradicating the pathogen. However, Mtb has evolved

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• experiments, transcriptomic profiling showed upregulation of the recA gene, which is known to be important for DNA repair, implicating that cisplatin could interfere with DNA replication in P. aeruginosa. Cisplatin treatment significantly repressed the type III secretion system (T3SS), which is important for

• of the LexA-controlled SOS regulon [31], including genes involved in DNA replication, recombination, modification and repair (dnaE2, imuB, imuA, dinG, recA, recN, recX) and genes involved in pyocin synthesis (PA0614-PA0648), whose expression were previously reported to be induced by ciprofloxacin [31

• further validate the impact of cisplatin on DNA replication, we compared the cisplatin sensitivity of the P. aeruginosa wild-type PAO1 strain and its DNA recombination-deficient recA mutant and found that the rec recombination pathway was essential for the cisplatin resistance in P. aeruginosa (Figure 4

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

• regulation of gene expression, DNA replication, signal transduction, virulence, etc. and therefore represent potential fruitful targets for antibacterial drug discovery. Recently, scientific efforts have helped towards the understanding and the deciphering of the protein-interaction networks (PINs) that

• ][53][54]. The β-clamp interacts with many different proteins such as several polymerases (e.g. I, II, III, IV, V and DnaE) and other proteins involved in DNA replication including DNA ligase and the replication regulatory protein Hda, all of which contain the conserved binding pentapeptide motif QL(S

• /D)LF (8, Figure 3) [55][56]. There are several reasons that make the bacterial clamp a promising and attractive target for the development of new antibiotics: it is essential for DNA replication and repair, it is highly conserved across the different bacterial pathogens and, most importantly from a

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• ], quinolines are only present in approximately 2% of FDA approved prescription pharmaceuticals [2]. Recently, 2,3,4-trisubstituted arylquinolines such as BI 224436 1 [3][4] and 2 [5][6] have been shown to exhibit inhibitory activity against HIV-1 integrase that is essential for viral replication through

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• ligand may interfere with DNA–enzyme recognition events, which are essential for DNA-based cellular processes, e.g., gene replication or transcription [1]. To this end, it was shown that DNA-binding ligands may operate as chemotherapeutic anticancer, antiviral or antibacterial drugs, for example as

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

• activities on a Berthold Technologies Centro XS3 Microplate Luminometer as indicators of viral genome replication and cell viability, respectively, as previously described [18]. Cytotoxic activity The cytotoxicity was evaluated by measuring the effect produced on cell morphology including the nuclei and cell