Welcoming Our New Editorial Advisory Board Chairs
We present our new set of Editorial Advisory Board Chairs: Anna K. H. Hirsch (HIPS Saarland), Sangyong Jon (KAIST), and Gianluca Sbardella (University of Salerno).PMID:38528748 | DOI:10.1002/cmdc.202400162 (Source: ChemMedChem)
Source: ChemMedChem - March 26, 2024 Category: Chemistry Authors: David Peralta Source Type: research
Uracil- and Pyridine-Containing HDAC Inhibitors Displayed Cytotoxicity in Colorectal and Glioblastoma Cancer Stem Cells
ChemMedChem. 2024 Mar 26:e202300655. doi: 10.1002/cmdc.202300655. Online ahead of print.ABSTRACTCancer stem cells (CSCs) are a niche of highly tumorigenic cells featuring self-renewal, activation of pluripotency genes, multidrug resistance, and ability to cause cancer relapse. Seven HDACi (1-7), showing either hydroxamate or 2'-aminoanilide function, were tested in colorectal cancer (CRC) and glioblastoma multiforme (GBM) CSCs to determine their effects on cell proliferation, H3 acetylation levels and in-cell HDAC activity. Two uracil-based hydroxamates, 5 and 6, which differ in substitution at C5 and C6 positions of the p...
Source: ChemMedChem - March 26, 2024 Category: Chemistry Authors: Francesco Fiorentino Emanuele Fabbrizi Alessia Raucci Beatrice Noce Rossella Fioravanti Sergio Valente Chantal Paolini Ruggero De Maria Christian Steink ühler Paola Gallinari Dante Rotili Antonello Mai Source Type: research
C9-Functionalized Doxycycline Analogs as Drug Candidates to Prevent Pathological α-Synuclein Aggregation and Neuroinflammation in Parkinson's Disease Degeneration
ChemMedChem. 2024 Mar 25:e202300597. doi: 10.1002/cmdc.202300597. Online ahead of print.ABSTRACTDoxycycline, a semi-synthetic tetracycline, is a widely used antibiotic for treating mild-to-moderate infections, including skin problems. However, its anti-inflammatory and antioxidant properties, combined with its ability to interfere with α-synuclein aggregation, make it an attractive candidate for repositioning in Parkinson's disease. Nevertheless, the antibiotic activity of doxycycline restricts its potential use for long-term treatment of Parkinsonian patients. In the search for non-antibiotic tetracyclines that could ope...
Source: ChemMedChem - March 25, 2024 Category: Chemistry Authors: Laurent Ferri é Bruno Figad ère Cl émence Rose Rodrigo Hern án Tomas-Grau Rosana Cheh ín Brenda Zabala Patrick Pierre Michel Rita Raisman-Vozari Jean-Michel Brunel Source Type: research
C9-Functionalized Doxycycline Analogs as Drug Candidates to Prevent Pathological α-Synuclein Aggregation and Neuroinflammation in Parkinson's Disease Degeneration
ChemMedChem. 2024 Mar 25:e202300597. doi: 10.1002/cmdc.202300597. Online ahead of print.ABSTRACTDoxycycline, a semi-synthetic tetracycline, is a widely used antibiotic for treating mild-to-moderate infections, including skin problems. However, its anti-inflammatory and antioxidant properties, combined with its ability to interfere with α-synuclein aggregation, make it an attractive candidate for repositioning in Parkinson's disease. Nevertheless, the antibiotic activity of doxycycline restricts its potential use for long-term treatment of Parkinsonian patients. In the search for non-antibiotic tetracyclines that could ope...
Source: ChemMedChem - March 25, 2024 Category: Chemistry Authors: Laurent Ferri é Bruno Figad ère Cl émence Rose Rodrigo Hern án Tomas-Grau Rosana Cheh ín Brenda Zabala Patrick Pierre Michel Rita Raisman-Vozari Jean-Michel Brunel Source Type: research
Developing Dynamic Structure-Based Pharmacophore and ML-Trained QSAR Models for the Discovery of Novel Resistance-Free RET Tyrosine Kinase Inhibitors
In this study, a structure-based dynamic pharmacophore-driven approach using E-pharmacophore modeling from molecular dynamics trajectories is proposed to select low energy favorable hypotheses, and ML-trained QSAR models to predict pIC50 values of compounds. For this aim, extensive small molecule libraries were screened using developed ligand-based models and potent compounds which are capable of inhibiting RET activation were proposed.PMID:38523069 | DOI:10.1002/cmdc.202300644 (Source: ChemMedChem)
Source: ChemMedChem - March 24, 2024 Category: Chemistry Authors: Ehsan Sayyah Lalehan Oktay H üseyin Tunç Serdar Durdagi Source Type: research
Structural analysis of the macrocyclic inhibitor BI-4020 binding to EGFR kinase
ChemMedChem. 2024 Mar 24:e202300343. doi: 10.1002/cmdc.202300343. Online ahead of print.ABSTRACTA novel macrocyclic inhibitor of mutant EGFR (BI-4020) has shown promise in pre-clinical studies of T790M and C797S drug-resistant non-small cell lung cancer. To better understand the molecular basis for BI-4020 selectivity and potency, we have carried out biochemical activity assays and structural analysis with X-ray crystallography. Biochemical potencies agree with previous studies indicating that BI-4020 is uniquely potent against drug-resistant L858R/T790M and L858R/T790M/C797S variants. Structures show that BI-4020 is likel...
Source: ChemMedChem - March 24, 2024 Category: Chemistry Authors: Tyler S Beyett Jaimin K Rana Ilse K Schaeffner David E Heppner Michael Eck Source Type: research
Phosphine-Catalyzed Synthesis and Cytotoxic Evaluation of Michael Adducts of the Sesquiterpene Lactone Arglabin
ChemMedChem. 2024 Mar 22:e202400045. doi: 10.1002/cmdc.202400045. Online ahead of print.ABSTRACTA general method for chemo- and diastereoselective modification of anticancer natural product arglabin with nitrogen- and carbon-centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s-cis-geometry of α-methylene-γ-butyrolactone moiety of arglabin favors for the additional stabilization of zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly efficient phosphine-catalyzed Michael additions to thi...
Source: ChemMedChem - March 22, 2024 Category: Chemistry Authors: Alexey Valeryevich Salin Andrey A Shabanov Khasan R Khayarov Daut R Islamov Alexandra D Voloshina Syumbelya K Amerhanova Anna P Lyubina Source Type: research
Development of benzimidazole-substituted spirocyclopropyl oxindole derivatives as cytotoxic agents: tubulin polymerization inhibition and apoptosis inducing studies
ChemMedChem. 2024 Mar 22:e202400052. doi: 10.1002/cmdc.202400052. Online ahead of print.ABSTRACTA series of spirocyclopropyl oxindoles with benzimidazole substitutions was synthesized and tested for their cytotoxicity against selected human cancer cells. Most of the molecules exhibited significant antiproliferative activity with compound 12p being the most potent. It exhibited significant cytotoxicity against MCF-7 breast cancer cells (IC50 value 3.14 ± 0.50 µM), evidenced by the decrease in viable cells and increased apoptotic features during phase contrast microscopy, AO/EB, DAPI and DCFDA staining studies. Compound 12...
Source: ChemMedChem - March 22, 2024 Category: Chemistry Authors: Akash P Sakla Mohd Rabi Bazaz Ashutosh Mahale Pravesh Sharma Durgesh Gurukkala Valapil Onkar Prakash Kulkarni Manoj P Dandekar Nagula Shankaraiah Source Type: research
Phosphine-Catalyzed Synthesis and Cytotoxic Evaluation of Michael Adducts of the Sesquiterpene Lactone Arglabin
ChemMedChem. 2024 Mar 22:e202400045. doi: 10.1002/cmdc.202400045. Online ahead of print.ABSTRACTA general method for chemo- and diastereoselective modification of anticancer natural product arglabin with nitrogen- and carbon-centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s-cis-geometry of α-methylene-γ-butyrolactone moiety of arglabin favors for the additional stabilization of zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly efficient phosphine-catalyzed Michael additions to thi...
Source: ChemMedChem - March 22, 2024 Category: Chemistry Authors: Alexey Valeryevich Salin Andrey A Shabanov Khasan R Khayarov Daut R Islamov Alexandra D Voloshina Syumbelya K Amerhanova Anna P Lyubina Source Type: research
Development of benzimidazole-substituted spirocyclopropyl oxindole derivatives as cytotoxic agents: tubulin polymerization inhibition and apoptosis inducing studies
ChemMedChem. 2024 Mar 22:e202400052. doi: 10.1002/cmdc.202400052. Online ahead of print.ABSTRACTA series of spirocyclopropyl oxindoles with benzimidazole substitutions was synthesized and tested for their cytotoxicity against selected human cancer cells. Most of the molecules exhibited significant antiproliferative activity with compound 12p being the most potent. It exhibited significant cytotoxicity against MCF-7 breast cancer cells (IC50 value 3.14 ± 0.50 µM), evidenced by the decrease in viable cells and increased apoptotic features during phase contrast microscopy, AO/EB, DAPI and DCFDA staining studies. Compound 12...
Source: ChemMedChem - March 22, 2024 Category: Chemistry Authors: Akash P Sakla Mohd Rabi Bazaz Ashutosh Mahale Pravesh Sharma Durgesh Gurukkala Valapil Onkar Prakash Kulkarni Manoj P Dandekar Nagula Shankaraiah Source Type: research
Phosphine-Catalyzed Synthesis and Cytotoxic Evaluation of Michael Adducts of the Sesquiterpene Lactone Arglabin
ChemMedChem. 2024 Mar 22:e202400045. doi: 10.1002/cmdc.202400045. Online ahead of print.ABSTRACTA general method for chemo- and diastereoselective modification of anticancer natural product arglabin with nitrogen- and carbon-centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s-cis-geometry of α-methylene-γ-butyrolactone moiety of arglabin favors for the additional stabilization of zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly efficient phosphine-catalyzed Michael additions to thi...
Source: ChemMedChem - March 22, 2024 Category: Chemistry Authors: Alexey Valeryevich Salin Andrey A Shabanov Khasan R Khayarov Daut R Islamov Alexandra D Voloshina Syumbelya K Amerhanova Anna P Lyubina Source Type: research
Development of benzimidazole-substituted spirocyclopropyl oxindole derivatives as cytotoxic agents: tubulin polymerization inhibition and apoptosis inducing studies
ChemMedChem. 2024 Mar 22:e202400052. doi: 10.1002/cmdc.202400052. Online ahead of print.ABSTRACTA series of spirocyclopropyl oxindoles with benzimidazole substitutions was synthesized and tested for their cytotoxicity against selected human cancer cells. Most of the molecules exhibited significant antiproliferative activity with compound 12p being the most potent. It exhibited significant cytotoxicity against MCF-7 breast cancer cells (IC50 value 3.14 ± 0.50 µM), evidenced by the decrease in viable cells and increased apoptotic features during phase contrast microscopy, AO/EB, DAPI and DCFDA staining studies. Compound 12...
Source: ChemMedChem - March 22, 2024 Category: Chemistry Authors: Akash P Sakla Mohd Rabi Bazaz Ashutosh Mahale Pravesh Sharma Durgesh Gurukkala Valapil Onkar Prakash Kulkarni Manoj P Dandekar Nagula Shankaraiah Source Type: research
Natural distribution, structures, synthesis, and bioactivity of hasubanan alkaloids
ChemMedChem. 2024 Mar 19:e202300721. doi: 10.1002/cmdc.202300721. Online ahead of print.ABSTRACTHasubanan alkaloids represent a distinct class of alkaloids bearing a structural resemblance to morphine, predominantly found in herbals of the Stephania genus. Their intriguing molecular architecture and potential analgesic properties have captured the interest of medicinal chemists worldwide. This review meticulously examines the natural distribution, structural characteristics, biosynthetic pathways, synthetic methodologies, and biological activities of hasubanans.PMID:38503694 | DOI:10.1002/cmdc.202300721 (Source: ChemMedChem)
Source: ChemMedChem - March 19, 2024 Category: Chemistry Authors: Yingjie Wang Fuxin Sun Yapeng Liang Di Zhou Gang Chen Ning Li Source Type: research
Iodinated 4,4'-bipyridines with antiproliferative activity against melanoma cell lines
ChemMedChem. 2024 Mar 15:e202300662. doi: 10.1002/cmdc.202300662. Online ahead of print.ABSTRACTIn the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. However, although bound iodine atoms are considered powerful HaB donors, few iodinated new drugs were reported so far. Recently, iodinated 4,4'-bipyridines showed interesting properties as HaB donors in solution and in the solid state. In this paper, a study on the inhibition activity of seven halogenated 4,4'-bipyridines against malignant melanoma (MM) cell proliferation is described. Explorative dose/respons...
Source: ChemMedChem - March 15, 2024 Category: Chemistry Authors: Paola Peluso Victor Mamane Ylenia Spissu Giuseppina Casu Alessandro Dess ì Roberto Dallocchio Barbara Sechi Giuseppe Palmieri Carla Rozzo Source Type: research
Iodinated 4,4'-bipyridines with antiproliferative activity against melanoma cell lines
ChemMedChem. 2024 Mar 15:e202300662. doi: 10.1002/cmdc.202300662. Online ahead of print.ABSTRACTIn the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. However, although bound iodine atoms are considered powerful HaB donors, few iodinated new drugs were reported so far. Recently, iodinated 4,4'-bipyridines showed interesting properties as HaB donors in solution and in the solid state. In this paper, a study on the inhibition activity of seven halogenated 4,4'-bipyridines against malignant melanoma (MM) cell proliferation is described. Explorative dose/respons...
Source: ChemMedChem - March 15, 2024 Category: Chemistry Authors: Paola Peluso Victor Mamane Ylenia Spissu Giuseppina Casu Alessandro Dess ì Roberto Dallocchio Barbara Sechi Giuseppe Palmieri Carla Rozzo Source Type: research
