Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• -spectrum antifungal agents. Among the many drugs and hits, the azole-based systems (including triazoles and imidazoles) are of particular importance in this context. Their mechanism of action is the inhibition of the activity of the enzyme lanosterol 14α-demethylase (CYP51), which is encoded by the CYP51

• /ERG11 gene. This enzyme contains a haem-like prosthetic group in its active center and is a member of the cytochrome P450 family, which plays a key role in the biosynthesis of sterols. Sterols in turn are integral components of the fungal cell membrane, making inhibition of CYP51 [43] an effective

• method of controlling fungal infections. The mechanism of inhibition of azoles and their derivatives is based on the formation of a coordination bond between their heterocyclic nitrogen atom, which carries an unshared electron pair, and the haem iron atom. The formation of this bond leads to inhibition

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

•  1), are recognized as a “privileged scaffold” in bioorganic and medicinal chemistry [1]. On the other hand, the 2-anilinoquinazolines have been less studied but our groups have developed recently the synthesis of new molecules of this family and discovered a compound (DB18) with a potent inhibition

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• [5][6][7][8][9][10][11][12][13]. For example, 2-hydroxymethyl-5-hydroxypyran-4-one (kojic acid) is a well-known skin whitening agent extensively used in the cosmetic, medicine and food industries. The action of this compound is based on inhibition of tyrosinase activity, which helps to protect

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• antioxidant properties were determined using the reaction with synthetic radicals, the cupric reducing antioxidant capacity assay, the inhibition process of superoxide radical anion formation by xanthine oxidase, and the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro. Keywords

• in the reaction with a diphenylpicrylhydrazyl (DPPH) radical, ABTS·+ radical cation, CUPRAC test, and inhibition process of superoxide radical anion formation by xanthine oxidase (NBT assay). The presence of a catechol fragment and thioether or thione groups determines the ability to neutralize

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• -methylalternariol derivative 15 was isolated from A. alternata and showed inhibitory activity against HCV NS3/4A protease (IC50: 52.0 μg/mL), cytotoxic activity against HEP-G2 cancer cells, and turned out to be antibacterial against Bacillus cereus, B. megaterium, and Escherichia coli with inhibition zones of 17

• sp. [172][180] and Rhizopycnis vagum [171]. Palmariol A and B showed weak antifungal activity against Mucor racemosus (8 mm inhibition zone at 20 μM/disc) and palmariol A was furthermore active against Bacillus subtilis (9 mm) [178]. Palmariol B was found to show a higher antimicrobial activity than

• fumigatus, A. niger, and Candida albicans (zones of inhibition: 16, 15, 12 mm, respectively, at 200 µg/disc) [229], and against Alternaria alternata (MIC: 1 µg/mL) [236]. It irreversibly inactivated Escherichia coli biotin protein ligase opening a potential application as antimicrobial or biocide [237]. It

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• treatment of Alzheimer's disease [3][4]. Likewise, RL91 and BHMPC are active for selective cell growth inhibition of the resistant lines (Figure 1) [5][6]. Their synthesis mainly involves a cascade Michael–aldol reaction between enones and suitable Michael donors such as β-ketosulfones, β-diketones, or

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• μM. Compounds 1–5 were merely inhibitory against tyrosinase, showing 19, 13, 9.6, 18, and 15% inhibition at 200 μM, respectively, while a positive control, kojic acid, inhibited the same enzyme by 95%. Conclusion In summary, five new alkylpyrroles, allostreptopyrroles A–E (1–5), were discovered from

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• , PF-06821497 showed potent tumor growth inhibition in mouse xenograft models [6]. CRA-680 was efficacious in both a house dust mouse model of allergic lung inflammation and a guinea pig allergen challenge model of lung inflammation [7]. In addition, isoquinolinone compounds not only prevent and

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• derivatives (mainly amides) exhibit various types of biological activity, among which the following can be highlighted: inhibition of β-lactamases [4][5], antitubercular properties [6], antiproliferative and antibacterial activity [7], herbicidal properties [8][9], inhibition of neutral amino acid transporter

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• improvement through inverse agonism at histamine receptor 3 (H3) using recombinant isoforms. This finding corrects their previous assumption of betahistidine acting as an antagonist. Inhibition of cAMP formation and [3H]arachidonic acid release concluded the inverse agonist role. Five-membered heteroaromatic

• acid (46). The major source of histamine are mast cells, although it is additionally biosynthesized in basophils, other immune cells, and tissues like intestinal mucosa, skin, or the heart [45][48]. Histamine plays many pivotal roles in the onset of allergies via Th2 cytokine secretion and inhibition

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• molecules have been used in diverse settings, functioning as organic field effect transistors [10][11][12], light-emitting diodes [13][14][15], organic semiconductors [16][17], organic photovoltaics [1][18][19][20][21][22], photocatalysts [23], and biological agents for tracking or inhibition [24][25], and

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• each bacterium at 10.5 µg/mL, where they showed no inhibition. The peptides exhibited no antibiotic activity against E. coli ATCC IM08B, C. difficile R20291, A. baumannii ATCC BAA 747, and MRSA at the concentrations employed. It was expected that the lack of effect on E. coli would occur, as the pre

• inhibition were averaged. The percentage of inhibition was derived by analyzing the 16 h growth curve data using the standard protocol established in our laboratory, comparing the growth curves obtained across the conducted experiments. All data processing and final figures were generated using Prism

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• heterocyclic moieties containing three or more (hetero)cycles. Moreover, many compounds are accompanied by data on their biological activities, such as antiproliferative, antimalarial, antimicrobial, antifungal, steroid antagonist, and enzyme inhibition, among others, aimed at furnishing pertinent insights for

• . The oxetane compound 6 was further derivatized to incorporate a pyrrolidine moiety in presence of ammonia. Upon debenzylation at C-3, the target compound 7 was obtained in an 18% overall yield from 3. The pyrrolidino-oxetane derivative exhibited potent inhibition of Hedgehog signaling, comparable to

• that compounds bearing hydrophobic fragments were superior inhibitors compared to those with polar groups. Additionally, some derivatives exhibited better activity than the reference compound, with more than 40% inhibition of the enzyme. The research group also described additional spiro products

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• higher yields of 84% and 71%, respectively. The steric inhibition of a doubly substituted phenyl ring was observed in a diminished formation of 2,6-dichlorobenzaldehyde (4m) in 39% yield. Naphthalen-2-ylmethanol gave aldehyde 4n in 44% yield. Pyridines 4o and 4p were also compatible and gave good yields

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• of RiPPs have a molecular weight between 1,000 and 5,000 Da. Peptide natural products exhibit high specificity and binding affinity to their corresponding targets [9][10]. The inhibition of protein–protein interactions is an emerging strategy in the development of novel therapeutics [11]. Binding to

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• antibiotic-sparing anti-infective drugs. Building synthetic glycoconjugates for the inhibition and modulation of bacterial lectins have shown promising results. Light-sensitive lectin ligands could allow the modulation of lectins activity with precise spatiotemporal control. Despite the potential of

• increasingly limited for treatment of infections. PA has been classified as a priority 1 pathogen by the WHO [2][3]. Various approaches to treating PA, in addition to traditional antibiotics, have been developed including inhibition of quorum sensing, biofilm formation, iron chelation, and interfering with

• formation [5][6][7][8]. Building synthetic glycoconjugates for the inhibition and modulation of bacterial lectins responsible for biofilm formation have shown promising results [9][10]. Unlike antibiotics, lectin inhibitors could prevent pathogenicity by interfering with virulence factors instead of killing

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• -ranging biological activities. Specifically, representative examples include fasicularin (IV, Figure 1), which possesses cytotoxic properties [21] and psammaplin B (V, Figure 1), which shows antimicrobial and mild tyrosine kinase inhibition activities [22]. In addition, Se-aspirin (VI, Figure 1) has been

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• immobilized building blocks. Biologically active pyrazole–triazole hybrids 1–4: inhibitory effect on cholera bacteria [13], antimicrobial properties [14], P2X7 antagonists (depression) [15] and ERK3 inhibition [12]. Synthesized triazole–pyrazole hybrids 21aa–vg. Literature-reported synthetic routes to

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• intermediate with a benzo[b]fluorene skeleton undergoes further conversion into fluostatins with a benzo[a]fluorene skeleton remains to be elucidated [27][28]. Inhibition of cofactor-independent catalytic activities of AlpJ-family oxygenases by superoxide dismutase There are many reported cofactor-independent

• substrates to activate molecular oxygen, leading to the generation of a substrate radical and the superoxide anion O2•− [29][33][37]. The well-established superoxide trapping agent superoxide dismutase (SOD) has demonstrated significant inhibition of the NMO-catalyzed monooxygenation reaction [29]. To probe

• products detected for AlpJ, Flu17, or JadG (Figure 2). Furthermore, a dose-dependent inhibition of the JadG-catalyzed reaction by SOD was observed (Figure S6, Supporting Information File 1). These findings support the presence of the superoxide anion O2•− and underscore the indispensable role in the

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• ) being active at 5 μg/mL, using a 75% cutoff inhibition at each concentration. On the other hand, MCF-7 and SK-MEL-28 cells were the most resistant ones, with no compound being active at the lower concentration (Figure 5). This evidence of selective cytotoxicity for a specific histological tumor subtype

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• inhibition of APOBEC3A was observed for modified DNAs. Although this shows that the negative charge is poorly accommodated in the active site of CDA and APOBEC3, the synthetic route reported here provides opportunities for the synthesis of other derivatives of phosphapyrimidine riboside for potential

• ][3][4][5]. Full inhibition of CDA leads to accumulation of toxic pyrimidine catabolism intermediates [6][7]. However, local and temporary inhibition of CDA in the liver provides a therapeutic benefit by allowing cytosine analogue-containing drugs to bypass the liver with an intact nucleobase

• leads to tumorigenesis in transgenic mouse models [24][28][34][35]. High levels of A3A and A3B mRNA are also linked to the more aggressive breast cancers, including triple negative cancers [36]. Since A3B is not essential for humans [37] and A3A does not take part in primary metabolism, inhibition of

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

• led to the corresponding carboxylic acids 24 and 29, and from there, the desired final compounds 4a,b were obtained in a straightforward two-step synthesis. Biochemical study: inhibition of SARS-CoV-2 RdRp We aimed to determine the inhibitory activity of the final compounds 2, 16, 3a–c and 4a,b

• activity, while the ring-opened derivative 16 showed inhibition with IC50 = 114.2 μM. It seemed that the significantly smaller size of the oxygen atom in the benzoxazole derivative compared to sulfur in HeE1-2Tyr (1) led to an unfavorable molecular shape, while the analogue with the open ring was able to

• compensate this difference. The pyridone derivatives 3a–c exerted an activity resulting in IC50 values of 128.7 μM, 203.8 μM and 88.1 μM, respectively, highlighting that even significantly truncated molecules are capable of RdRp inhibition. A thiophene substituent in position 5 (i.e., 3c) proved to be the

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• isolated from a sea sponge, Plakortis simplex [3][4]. Wortmannin, which also has a furan, was isolated from Penicillium wortmannin and shows anticancer activity via potent inhibition of phosphoinositide 3-kinase [5]. These are just a handful of the bioactive natural products containing furans that exist

(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

• does not change the aqueous solubility (KS), it does improve the intrinsic clearance rate in human liver microsomes (CLint) and the half-live in human liver microsomes (t1/2). Additionally, undesired target inhibition was reduced by isosteric replacement of meta-benzene with 1,5-BCHeps as shown by the

• 50% inhibition concentration of selected CYP450 enzymes (IC50). Cis-2,6-disubstituted [2]-ladderanes Brown and co-workers recently proposed cis-2,6-disubstituted bicyclo[2.2.0]hexanes ([2]-ladderanes) as isosteric replacements for meta-benzenes. An exit vector analysis indicated that the substituent

• both 189 and iso-189 in form of the inhibition of prostaglandin PGE2 synthesis by cyclooxygenase-2 (COX-2). Their investigation showed that while 1,3-cuneane 189 requires a 100-fold increase in concentration to reach inhibitory rates comparable to ketoprofen, its isomer iso-189 is inactive against COX