ArtikelAnion–π Type Aggregation‐Induced Emission Luminogensvon Guoyu Jiang et al. · 14.03.2023 Herein we highlight the design of anion–π type luminogens with aggregation-induced emission feature (AIEgens) by using anion–π interactions to impede the π–π interactions. Applications of these anion–π type AIEgens in wash-free bioimaging and long-t...
ArtikelInvestigating the Lack of Translation from Cruzain Inhibition to Trypanosoma cruzi Activity with Machine Learning and Chemical Space Analysesvon Rafael F. et al. · 14.03.2023 The lack of translation of cruzain biochemical activity to the biological activity on Trypanosoma cruzi is investigated with machine learning. The figure shows a density plot on the t-SNE projection of the chemical space of active compounds (pIC50 &...
ArtikelSynthesis and Structural Characterization of Macrocyclic Plasmin Inhibitorsvon Simon J. et al. · 14.03.2023 New macrocyclic plasmin inhibitors containing a C-terminal P1 benzylamine group were synthesized. Their N-terminal substitution provided analogues with sub-nanomolar K i values. Additional inhibitors containing an asymmetric linker possess K i value...
ArtikelDiscovery of a Chemical Probe to Study Implications of BPTF Bromodomain Inhibition in Cellular and in vivo Experimentsvon Paola Martinelli et al. · 14.03.2023 Unraveling the complex role of BPTF: Herein we report the discovery of BI-7190, a potent and selective chemical probe targeting the bromodomain of BPTF with an attractive pharmacokinetic profile enabling cellular and in vivo experiments in mice. A...
ArtikelInhibition Studies on Carbonic Anhydrase Isoforms I, II, IX, and XII with a Series of Sulfaguanidinesvon Morteza Abdoli et al. · 14.03.2023 Sulfaguanidine derivatives as a new class of carbonic anhydrase (CA) inhibitors show selective inhibition of cancer-associated isoforms CA IX and CA XII. In addition to great selectivity, both series of sulfaguanidines studied exhibit nanomolar inhi...
Artikel2‐Hydroxy‐4‐benzyloxylimine Resveratrol Derivatives as Potential Multifunctional Agents for the Treatment of Parkinson's Diseasevon Zhongcheng Cao et al. · 14.03.2023 The combination of ortho hydroxyimine resveratrols with aryl benzyl ethers afforded 2-hydroxy-4-benzyloxyimine resveratrol derivatives. Representative compound 7 h exhibited good MAO-B inhibition, antioxidant activity, biometal chelating ability, ne...
ArtikelHydrazone‐Tethered 5‐(Pyridin‐4‐yl)‐4H‐1,2,4‐triazole‐3‐thiol Hybrids: Synthesis, Characterisation, in silico ADME Studies, and in vitro Antimycobacterial Evaluation and Cytotoxicityvon Ogunyemi O. et al. · 14.03.2023 A small set of hydrazone-linked arylpyrrole-1,2,4-triazole compounds was synthesised and evaluated against Mycobacterium tuberculosis. The most promising compound, the derivative without the benzene ring appended to the pyrrole unit, displayed accep...
ArtikelFront Cover: Synthesis and Structural Characterization of Macrocyclic Plasmin Inhibitors (ChemMedChem 6/2023)von Simon J. et al. · 14.03.2023 The Front Cover shows new macrocyclic plasmin inhibitors containing a C-terminal P1 benzylamine group. Their N-terminal substitution provided analogues with sub-nanomolar K i values. Additional inhibitors containing an asymmetric linker possess K i ...
ArtikelA Single‐Atom Nanozyme Cascade for Selective Tumor‐Microenvironment‐Responsive Nanocatalytic Therapyvon Rasmi Morajkar et al. · 14.03.2023 Nanomedicinal research holds significant potential in the development of new cancer therapeutics. Nanozymes can be promising anticancer agents due to their tunable enzyme-like properties. This highlight features a recently reported bioinspired const...
ArtikelSynthesis and Biological Activities of 11‐ and 12‐Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB and Tyrosyl‐DNA Phosphodiesterase 1 Inhibitorsvon Hao Yang et al. · 18.03.2023 A structure–activity relationship study of 11- or 12-substituted benzophenanthridinone derivatives led to the identification of potent a dual topoisomerase 1 and tyrosyl-DNA phosphodiesterase 1 inhibitor (43), which can enhance the ability of topote...
ArtikelBenocyclidine (BTCP) as Non‐labelled Reporter Ligand for MS Binding Assays for the PCP Ion Channel Binding Site of the Desensitized Torpedo Nicotinic Acetylcholine Receptor (nAChR)von Mark Währa et al. · 18.03.2023 We present the first MS Binding Assays addressing the PCP ion channel binding site of the nicotinic acetylcholine receptor as a substitute for radioligand binding assays utilizing radioligands such as [3H]PCP or [3H]TCP. Because BTCP has distinctly ...
ArtikelSingle Modification at the N‐Terminus of Norvancomycin to Combat Drug‐Resistant Gram‐Positive Bacteriavon Dongliang Guan et al. · 14.03.2023 The introduction of an optimal single modification at the N-terminus of norvancomycin, especially an aromatic-sulfonium moiety, endowed the parent norvancomycin with 16- to 2048-fold enhancement in antibacterial activity against vancomycin-resistant...
ArtikelA Critical Study on Acylating and Covalent Reversible Fragment Inhibitors of SARS‐CoV‐2 Main Protease Targeting the S1 Site with Pyridinevon Rebekka Wamser et al. · 13.03.2023 In the search for suitable S1 binding fragments of SARS-CoV-2 Mpro, pyridine-electrophile combinations with different linkers (L, X) were tested regarding their activity, kinetics and chemical stability. Halopyridinyl esters showed high activity but...
ArtikelDouble BAC and Triple BAC: A Systematic Analysis of the Disinfectant Properties of Multicationic Derivatives of Benzalkonium Chloride (BAC)von Zachary E. et al. · 13.03.2023 BAC to the future: Benzalkonium chloride (BAC) has been a staple of modern disinfection for decades, but its shortcomings are becoming more evident. A direct comparison of the antimicrobial activity and toxicity of multicationic analogs of BAC has b...
ArtikelScouting Different Phosphodiesterase 4 Inhibitor Chemotypes in Silico To Guide the Design of Anti‐inflammatory/Antioxidant Agentsvon Elena Cichero et al. · 10.03.2023 Based on the X-ray data of previous phosphodiesterase 4 (PDE4) inhibitors, compounds 1–3 were designed, synthesized, and screened in silico as putative PDE4 inhibitors to exploit structural variation at the catechol group to gain further contacts, e...
ArtikelKinase Degraders, Activators, and Inhibitors: Highlights and Synthesis Routes to the Chemical Probes on opnMe.com, Part 1von Andreas Gollner et al. · 10.03.2023 To be continued: We present the synthesis routes to the 12 chemical probes that target kinases currently available on Boehringer Ingelheim's Open Innovation Portal, opnMe.com. This is Part 1 in a series that releases the syntheses of all chemical pr...
ArtikelDevelopment of Enterovirus Antiviral Agents That Target the Viral 2C Proteinvon Rishabh Kejriwal et al. · 10.03.2023 The Enterovirus (EV) genus includes several important human and animal pathogens. We report new antiviral compounds that target the conserved non-structural viral protein 2C with low micromolar to nanomolar IC50 values. The selection of resista...
ArtikelNot Every Hit‐Identification Technique Works on 1‐Deoxy‐d‐Xylulose 5‐Phosphate Synthase (DXPS): Making the Most of a Virtual Screening Campaignvon Sandra Johannsen et al. · 10.03.2023In this work, we demonstrate how important it is to investigate not only on-target activity but to keep antibiotic activity against critical pathogens in mind. Since antimicrobial resistance is spreading in bacteria such as Mycobacterium tuberculosis...
ArtikelDevelopment of Light Activated LXR Agonistsvon Dirk Trauner et al. · 10.03.2023Activation of the oxysterol-sensing transcription factor liver X receptor (LXR) has been studied as a therapeutic strategy in metabolic diseases and cancer but is compromised by the side effects of LXR agonists. Local LXR activation in cancer treatme...
ArtikelCYP3A4 catalyzes the rearrangement of the dual orexin receptor antagonist daridorexant to 4‐hydroxy piperidinol metabolitesvon Alexander Treiber et al. · 09.03.2023The dual orexin receptor antagonist daridorexant was approved in 2022 in the USA and EU for the treatment of insomnia. The purpose of this study was the identification of its metabolic pathways and the human cytochrome P450 (P450) enzymes involved in...
ArtikelThe European Federation for Medicinal Chemistry and Chemical Biology (EFMC) Best Practice Initiative: Hit Generationvon Jean Quancard et al. · 09.03.2023 Panning for gold in drug discovery: Hit generation aims at identifying the golden nuggets in the available chemical space to modulate a target of interest. The quality of these hits will have a major impact on the speed and success of drug discovery...
ArtikelDesign, synthesis, and optimization of new indole acetic acid derivatives as potent and selective CRTH2 receptor antagonists: the discovery of ACT‐774312von Hamed Aissaoui et al. · 08.03.2023Herein we report the structure-activity relationship (SAR) studies and optimization of new highly potent and selective CRTH2 receptor antagonists as potential follow-ups of our previous reported clinical candidate setipiprant (ACT-129968) for the tre...
ArtikelA Reinvestigation of the Role of the Sorbic Acid Tail on the Antibacterial and Anti‐Tuberculosis Properties of Moiramide Bvon Irina Kollmorgen et al. · 08.03.2023Due to worldwide increasing resistances, there is a considerable need for antibacterial compounds with modes of action not yet realized in commercial antibiotics. One such promising structure is the acetyl-CoA carboxylase (ACC) inhibitor moiramide B...
ArtikelIncorporation of Trifluoromethyltriazoline in the Side Chain of 4‐Aminoquinolines: Synthesis and Evaluation as Antiplasmodial Agentsvon Kanchan Yadav et al. · 08.03.2023Reported herein is the identification of a novel class of 4-aminoquinoline-trifluormethyltriazoline compounds as possible antiplasmodial agents. The compounds have been accessed through an Ag-catalyzed three-component reaction of trifluorodiazoethane...
ArtikelRecent Development of Copper (II) Complexes of Polypyridyl Ligands in Chemotherapy and Photodynamic Therapyvon Jansi Rani et al. · 07.03.2023 Light and redox: Herein we discuss the past ten years of research into copper complexes of terpyridine-, 2,2’-bipyridine-, and 1,10-phenanthroline-based ligands as potential anticancer agents. The aspects of chemotherapy by redox-mediated pathways a...
ArtikelDesign of OSMI‐4 Analogs Using Scaffold Hopping: Investigating the Importance of the Uridine Mimic in the Binding of OGT Inhibitorsvon Cyril Balsollier et al. · 02.03.2023 β-N-Acetylglucosamine transferase (OGT) is a promising therapeutic target. The first nanomolar OGT inhibitor, OSMI-4, is still the most potent inhibitor reported to date, yet its physicochemical properties limit its utility as a potential drug candi...
ArtikelBioisosterism: 1,2,4‐Oxadiazole Ringsvon Merve Camci et al. · 02.03.2023 Bioisosterism is critical for providing a broad perspective in the discovery of new drug molecules. The 1,2,4-oxadiazole ring is used as a bioisostere for ester and amide groups due to its resistance to hydrolysis, yet this ring is not limited to es...
ArtikelAnticancer Activities of Tetrasubstituted Imidazole‐Pyrimidine‐Sulfonamide Hybrids as Inhibitors of EGFR Mutantsvon Eman M. et al. · 01.03.2023 A novel set of tetrasubstituted imidazole-containing pyrimidine sulfonamide pharmacophores has been rationalized for their anticancer activities. Certain compounds were found to be potent HER2 blockers comparable to staurosporine, with anticancer ac...
ArtikelRuthenium‐Catalyzed Cycloaddition for Introducing Chemical Diversity in Second‐Generation β‐Lactamase Inhibitorsvon Flavie Bouchet et al. · 28.02.2023 Ruthenium(II)-catalyzed cycloaddition (RuAAC) is a powerful way to access 1,5-disubsituted and 1,4,5-trisubstituted triazole DBOs with complete control of regioselectivity. The biological activity of di- and tri-substituted DBOs gave promising activ...
ArtikelHistidinal‐Based Potent Antimalarial Agentsvon Chhuttan L. et al. · 28.02.2023 Several analogs of a novel class of histidinal-based antimalarial agents were synthesised. Among them, compounds 8 g, 8 h, and 15 exhibited superior antimalarial activity. Docking studies revealed that these antimalarial agents strongly interact wit...
ArtikelSystematic Potency and Property Assessment of VHL Ligands and Implications on PROTAC Designvon Johannes Krieger et al. · 28.02.2023 Our study describes a systematic evaluation of structure-activity-relationships and structure-property-relationships for VHL ligand designs. With a particular focus on exit vector analysis, we used our gained knowledge to design a small library of h...
ArtikelDesign and Synthesis of 1,3‐Diynes as Potent Antifungal Agents Against Aspergillus fumigatusvon Lakshmi Goswami et al. · 28.02.2023Eugenol and isoeugenol, secondary metabolites isolated from the plant Myristica fragrans have displayed antifungal activities against Aspergillus fumigatus (IC50 1900 μM). Compounds having conjugated unsaturation have been of great use as antifungals...
ArtikelFacile, single step synthesis of a series of D‐ring ethisterone substituted with 1,4‐1,2,3‐triazoles. Preliminary evaluation of their cytotoxic activities.von Daniel Canseco et al. · 28.02.2023A series of new D-ring ethisterone substituted with 1,4-1,2,3-triazoles were obtained in a facile manner via click chemistry reactions. The new compounds were characterized by multinuclear-NMR and mass spectrometry and unequivocally by single crystal...
ArtikelTerpyridine Glycoconjugates and Their Metal Complexes: Antiproliferative Activity and Proteasome Inhibitionvon Roberta Panebianco et al. · 27.02.2023 Sugars and metals: Terpyridine glycoconjugates have proven to be potential antitumor agents. Our results highlight that Cu(II) and Fe(II) ternary complexes of terpyridine derivatives have antiproliferative activity in the micromolar range. Additiona...
ArtikelDiscovery of Antitrypanosomal Indolylacetamides by a Deconstruction–Optimization Strategy Applied to Paullonesvon Jens et al. · 27.02.2023The parasitic kinetoplastid diseases Leishmaniasis, Chagas disease and Human African Trypanosomiasis constitute serious threats for populations throughout the (sub-)tropics. Most available drugs to treat these diseases possess inadequate properties a...
ArtikelDiscovery of SI 1/20 and SI 1/22 as Mutual Prodrugs of 5‐Fluorouracil and Imidazole‐Based Heme Oxygenase 1 Inhibitor with Improved Cytotoxicity in DU145 Prostate Cancer Cellsvon Loredana Salerno et al. · 24.02.2023 Heme oxygenase 1 (HO-1) is an enzyme that is overexpressed in many cancers, contributing to their spread and invasiveness; therefore, HO-1 inhibition is a promising approach in cancer chemotherapy. 5-Fluorouracil (5-FU) is a well-known antimetabolit...
ArtikelMultifaceted Target Specificity Analysis as a Tool in Antimicrobial Drug Development: Type III Pantothenate Kinases as a Case Studyvon Siobhan Ernan et al. · 22.02.2023 Multifaceted Target Specificity Analysis (MTSA) was developed as a tool for evaluating inhibitor interactions with homologous targets in closely related organisms to allow for a prediction on the likelihood that an antimicrobial developed using a ta...
ArtikelImidazo[1,2‐a]pyridine Derivatives as AMPK Activators: Synthesis, Structure–Activity Relationships, and Regulation of Reactive Oxygen Species in Renal Fibroblastsvon Siming Wu et al. · 22.02.2023 Drug design efforts led to the synthesis of a series of imidazo[1,2-a]pyridines as adenosine 5′-monophosphate activated protein kinase (AMPK) activators. The most potent compound showed an EC50 value of 11.0 nM against AMPK and significantly reduced...
ArtikelRu(II) Complexes with Enaminone Structures for Rapid Sterilization of Staphylococcus aureus and MRSA with Little Accumulation of Drug Resistancevon Yao Jian et al. · 21.02.2023 There is an urgent need to develop antibiotics with new chemical structures and antibacterial mechanisms, especially those that elicit little drug resistance after long-term use. Herein we report Ru(II) complexes containing enaminone structures that...
ArtikelThresholding DNA Nanomachine as a Highly Cooperative and Efficient Enzyme‐Like System for Controlled RNA Cleavagevon Christina Patra et al. · 13.02.2023 A tile-attached platform transforms a multicomponent enzymatic system into a single-unit enzymatic system. This leads to an increase in the system's overall cooperativity which, as expected, enhances its RNA cleavage activity and its stability in th...
ArtikelAcridine/Acridone–Carborane Conjugates as Strong DNA‐Binding Agents with Anticancer Potentialvon Daria Różycka et al. · 10.02.2023 Increasing ROS: A series of novel acridine/acridone-carborane conjugates were synthesised and investigated. Conjugate 30, containing meta-carborane, revealed dual activity as the most potent ct-DNA intercalator (with preservation of B-form DNA) and ...
ArtikelChallenges Based on Antiplasmodial and Antiviral Activities of 7‐Chloro‐4‐aminoquinoline Derivativesvon Satoshi Mizuta et al. · 08.02.2023 Chloroquine (CQ) has displayed the potential to inhibit malaria and virus infections. We designed and synthesized 7-chloro-4-aminoquinoline derivatives, which were synthesized and evaluated for their antiviral and antimalarial properties. Most of th...
ArtikelSecond‐Generation CD73 Inhibitors Based on a 4,6‐Biaryl‐2‐thiopyridine Scaffoldvon Rayane Ghoteimi et al. · 07.02.2023 New chemotype: A series of 4,6-biaryl-2-thiopyridine derivatives were designed as potential CD73 allosteric inhibitors. Three derivatives incorporating morpholino substituents showed improved aqueous solubility, and among them, two compounds were ab...
ArtikelThiazolidinone‐Heterocycle Frameworks: A Concise Review of Their Pharmacological Significancevon Pule Seboletswe et al. · 06.02.2023 Privileged hybrids: Thiazolidinone is one of the privileged pharmacophores in medicinal chemistry and is associated with various biological activities; it forms a functional unit in several FDA-approved drugs. Consequently, this pharmacophore has at...
ArtikelDesign, Synthesis, and Biological Evaluation of 2‐Aminothiazole Derivatives as Novel Checkpoint Kinase 1 (CHK1) Inhibitorsvon Minjie Deng et al. · 03.02.2023 Anticancer agents: In this work, a series of 2-aminothiazole derivatives were designed as novel CHK1 inhibitors by using a bioisosterism strategy. The most promising compound 8 n (shown) exhibited potent CHK1 inhibition, excellent anti-proliferative...
ArtikelExploration of the Binding Modes of Toll‐Like Receptor 4 Competitive Inhibitors: A Combined Ligand‐Based and Target‐Based Approachvon Wen Dang et al. · 31.01.2023 As a pattern-recognition receptor in mammals, toll-like receptor 4 (TLR4) plays an important role in recognizing pathogens. The current study explores inhibition of the TLR4–MD-2 interaction as a potential strategy for treating inflammatory disorder...
ArtikelThe Ups and Downs in Drug Design: Adventures in Medicinal Chemistry. By Victor E. Marquezvon Kenneth A. · 27.01.2023 CRC Press, Boca Raton, 2021. 452 pp., hardcover, €298.00.– ISBN 978-1032063638
ArtikelDesign and Synthesis of Highly Potent and Specific ABHD6 Inhibitorsvon Michael S. et al. · 06.09.2021 ABHD6 signature templates: We report tetrahydroisoquinoline and isoindoline “signature templates” for ABHD6 with single-digit nanomolar inhibitory and specificity for the target, and >1000-fold selectivity against serine hydrolase MGL and FAAH. O...
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