Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• and death, as 80% of deaths in this region were children under five [1]. Whilst there are drugs available for the treatment of malaria infections, most have now succumbed to parasite drug resistance and thus reduced clinical efficacy [2][3]. Consequently, new antiplasmodial drugs with novel malaria

• targets are urgently needed to combat the global problem of parasite drug resistance. For more than 10 years, the Open Source Malaria (OSM) consortium [4] has had an interest in identifying and developing novel antimalarial compounds that belong to a variety of chemotypes, one of which includes the 1,2,4

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• [98][99][100]. Preliminary biological screening indicates that members of this class are able to overcome multidrug resistance in vincristine resistant cells [98][99][100]. To access the common scaffold 188, the group relied on an intramolecular gold-photocatalyzed radical-mediated cyclization of an α

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• proven to be of clinical, health, industrial research and agrochemical importance [7][8][9][10][11][12]. Interestingly, the resistance of Bacillus spores to heat, radiation, and disinfection coupled with an inherent biosynthetic potential that enables them to grow even in the presence of antibiotics such

• it is important not to overlook Bacillus and their natural products especially in this current era of spreading antibiotic resistance and demands for ecologically friendly pest control strategies. Primary structure of digyalipopeptide A (1). Key COSY and HMBC correlations for compound 1. Key TOCSY

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

• , selective, and potent anti-HIV activity, however, it failed in phase IIb clinical trials due to viral resistance [28][29][30][31]. Even so, this class of natural products has great antiviral potential and its chemical modification could lead to new, efficient, and safe therapeutic resources. In this

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• biological activities, their antibacterial effect is more prominent. As we know, antimicrobial agents are a significant source to overcome bacterial infections, but overuse will lead to drug resistance [8], so it is necessary to synthesize new antibacterial compounds to overcome this problem. Quinolines

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• of alginate overproduction contributes to the PA biofilm environment and the resultant and deleterious bacterial resistance to current antibiotic treatments [2]. Alginate production is therefore established as a major virulence factor within PA respiratory tract infections for CF sufferers, and

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

Thermally activated delayed fluorescence (TADF) emitters: sensing and boosting spin-flipping by aggregation

• Ashish Kumar Mazumdar,
• Gyana Prakash Nanda,
• Nisha Yadav,
• Upasana Deori,
• Upasha Acharyya,
• Bahadur Sk and
• Pachaiyappan Rajamalli

Beilstein J. Org. Chem. 2022, 18, 1177–1187, doi:10.3762/bjoc.18.122

• sensitive to acidic protons. Hence, the exposure to acid and base vapors using trifluoroacetic acid (TFA) and triethylamine (TEA) led to solid-phase fluorescence switching with fatigue resistance. The current study demonstrates the role of the donor strength and size in tuning ΔEST in the aggregated state

• ) vapor for 6 s (Figure 6a). The reversible color switching was upheld with fatigue resistance for multiple cycles. Similarly, the film of BPy-p3C showed reversible changes of the fluorescence from green to dark upon successive exposure to TFA and TEA vapors (Figure 6c). To understand the effect of an

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• -substituted glycines [1][2]. They retain the same backbone as peptides except that the side chains are located on the nitrogen atoms of the amide bonds and thus represent an important class of peptide biomimetics [3][4][5], generally with improved cell permeability [6] and proteolytic resistance [7][8

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• field that penetrates the resistance of a magnetically conducting receiver and releases energy through the Joule effect [21][22]. The heating power in eddy currents is directly correlated with the square of the applied frequency and field amplitude. In contrast to the two previous effects, the

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• , Staphylococcus aureus, Klebsiella pneumoniae, and Staphylococcus pneumoniae were responsible for most of bacteremia deaths related to antimicrobial resistance in 2019 [2]. Current antibacterial drugs are facing various challenges, due to the inability to accumulate inside human cells made them inactive [3] and

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• decades because of its efficacy, safety, and low cost. However, the widespread resistance of Plasmodium falciparum to chloroquine has hampered efforts to combat malaria [2] resulting in artemisinin-based combination therapies as currently recommended standard. Notably, the use of chloroquine

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• artemisinin derivatives [7]. The emergence of drug resistance makes the efficacy of these drugs decline year by year, forcing scientists to constantly search for new antimalarial drugs [8][9][10]. In recent years, Iwasaki and co-workers have reported three novel linear lipopeptide natural products

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• electron-withdrawing group that enhances the effects of many bioactive molecules due to a significant improvement in stability, lipophilicity, and resistance to enzymatic degradation [17][18]. Also, it has been widely applied as a special alkyl substituent for ligands of phosphorescent heavy metal

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• . Interestingly, macrocyclic bisbenzylisoquinolines such as tetrandrine [48][49] and related alkaloids [50], have been reported to inhibit P‐glycoprotein (P-gp), a crucial factor of multidrug resistance in cancer. This is noteworthy as multidrug resistance is still a major problem in cancer therapy and no

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

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

• ; pseudomonine; Pseudomonas sp.; vancomycin-sensitive Enterococcus faecium; Introduction The introduction of antimicrobial drugs in the mid-20th century has had an unprecedented positive impact on human health, but the current threat of multiple drug resistance may well roll back all these past achievements [1

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

• cost-effective drug. Due to its impressive antimicrobial activity and limited adverse effect metronidazole (1) has been considered as a “Gold Standard” antibiotic (Figure 1). However, to avoid the problem related to clinical resistance to this antimicrobial agent some novel and improved analogues of

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• the transduction of signals; these processes induce cell apoptosis [8][9]. As mutations in the BCR-Abl-1 enzyme domain can occur, cases of resistance have emerged in the treatment with TKIs, compromising its effectiveness [10][11]. In continuation of the work by our group to develop new imatinib

• the 1,2,3-triazole core strategically in the design of new compounds [18][19]. The explanation for this interest is associated with its resistance towards oxidation, reduction, and acidic or basic hydrolysis reactions that occur in phase I of human metabolism [20][21]. The application of this core

• through isosterism (classical or non-classical) in the design of new active compounds has shown good results [22][23]. Specifically, in the development of new inhibitors for the treatment of cancer [24], its use is associated with producing compounds able to overcoming resistance (primary or secondary

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has

• table design showing which modification has duplex stabilizing properties, as well as improved nuclease resistance and cell activity, has been chosen for optimal visual presentation. This approach has spurred considerable interest since the introduction of positively charged groups results in ASOs with

• membrane permeability of ASOs. A reduction in the net negative charge may have beneficial delivery-related effects in addition to other possible effects such as improved resistance towards nuclease degradation or increased binding to the negatively charged RNA complements, the latter as a result of reduced

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• [72]. It was further shown to be cytotoxic and inhibiting cell cycle progression at G2/M phase [163]. Fumitremorgin C was shown to effect mammalian cells and inhibit the breast cancer resistance protein which imparts multidrug resistance and thus resistance to chemotherapeutics in breast cancer

• cross-resistance helvolic acid is of great pharmaceutical importance. On the other hand, these antibiotic activities of HA could alter the soil microflora in natural habitats, an ecological role of HA that requires further investigation. Pyripyropene A Pyripyropene A (PPPA) (24) belongs to the

• . fumigatus was driven by its pathobiology, e.g., a role in cytotoxicity, immunosuppression or antifungal drug resistance. In natural habitats these molecules may fulfill analogous functions, such as the defense against phagocytic predators by gliotoxin [78][79][80][81][82]. Indeed, the need for survival is

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

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

• stability, and fluorescence properties. The incorporation of the double-headed nucleosides 151a–d and 154a,b into oligonucleotides failed to form thermostable duplexes with complementary DNA and RNA strands but exhibited a potential resistance towards 3′-exonuclease. The synthesized double-headed

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

• modifications provide improved resistance to degradation by exo- and endonucleases and they both affect protein binding [16][17]. Eight of the now approved 13 oligonucleotide drugs feature the PS modification in the backbone and all four approved siRNA therapeutics: ONPATTRO® (patisiran, 2018), GIVLAARI

• '-aminonucleoside couples to the 5'-H-phosphonate in the presence of a base (Scheme 1) [64]. In comparison with natural phosphodiester oligonucleotides, these modified oligonucleotides display improved nuclease resistance and an enhanced duplex thermal stability of 2.3–2.6 °C per linkage independent of nucleotide

• the 3'-overhang region show enhanced endonuclease and 3'-exonuclease resistance [80]. Thus far, the AM1 modification has not found great success in antisense therapeutics, owing to RNAse H not recognizing a uniformly modified AM1-DNA:RNA heteroduplex. Recently, however, an 18-mer AM1-DNA gapmer was