Lysophosphatidic acid receptor 1 (LPA1) antagonists as potential migrastatics for triple negative breast cancer
In this study, we report the synthesis and biological evaluation of fluorine-containing triazole derivatives as potent LPA1 antagonists, offering potential as migrastatic drugs for triple negative breast cancer (TNBC). In particular, compound 12f, the most potent and highly selective in this series with an IC50 value of 16.0 nM in the cAMP assay and 18.4 nM in the calcium mobilization assay, inhibited cell survival, migration, and invasion in the TNBC cell line. Interestingly, the compound did not induce apoptosis in TNBC cells and demonstrated no cytotoxic effects. These results highlight the potential of LPA1 as a migras...
Source: ChemMedChem - April 22, 2024 Category: Chemistry Authors: Wenjie Liu Amr Abdullah Kamel Mousa Austin M Hopkins Yin Fang Wu Kelsie L Thu Michael Campbell Simon J Lees Rithwik Ramachandran Jinqiang Hou Source Type: research
Exploring Raloxifene-based Metallodrugs: A Versatile Vector Combined with Pt(II), Palladium(II) and Nickel(II) Dichlorides and Carborates against Triple-Negative Breast Cancer
This study provides valuable insights into the development of hybrid therapeutics against TNBC.PMID:38642018 | DOI:10.1002/cmdc.202400006 (Source: ChemMedChem)
Source: ChemMedChem - April 20, 2024 Category: Chemistry Authors: Aleksandr Kazimir Tom G ötze Peter L önnecke Blagoje Murgani ć Sanja Mijatovi ć Danijela Maksimovi ć-Ivanić Evamarie Hey-Hawkins Source Type: research
Rational Design and Synthesis of Isatin-Chalcone Hybrids Integrated with 1H-1,2,3-Triazole: Anti-proliferative Profiling and Molecular Docking Insights
In this study, a series of isatin-chalcone linked triazoles were synthesized using Cu-promoted Azide-Alkyne Cycloaddition (CuAAC) reaction and evaluated for their cytotoxicity against various cancer cell lines. The most potent compound displayed approximately 2.5 times greater activity compared to both reference compounds against ovarian cancer cell lines. These findings were supported by caspase-mediated apoptosis and molecular docking analyses. Docking revealed comparable VEGFR-2 affinities for 5b and 5-FU but highlighted stronger interaction of 5b with EGFR, evident from its lower docking score. Overall, these results s...
Source: ChemMedChem - April 19, 2024 Category: Chemistry Authors: Vipan Kumar Swati Swati Asif Raza Shefali Chowdhary Amit Anand Shaveta Shaveta Arun Sharma Kewal Kumar Source Type: research
Recent Development of Transition Metal Complexes as Chemotherapeutic Hypoxia Activated Prodrug (HAP)
ChemMedChem. 2024 Apr 18:e202400127. doi: 10.1002/cmdc.202400127. Online ahead of print.ABSTRACTHypoxia is a state characterized by low concentration of Oxygen. Hypoxic state is often found in the central region of solid tumors. Hypoxia is associated with abnormal neovascularization resulted in poor blood flow in tissues and increased proliferation of tumor cells, imbalance between O2 supply and O2 consumption in tumor cells, high concentration of proton and strong reducibility. And, these abnormalities enhance the survival potency of the hypoxic tumours and increase the resistance towards chemotherapy and radiotherapy. On...
Source: ChemMedChem - April 18, 2024 Category: Chemistry Authors: K Jagathesan Sovan Roy Source Type: research
Developing Low Molecular Weight PET and SPECT Imaging Agents
This article describes the general development path leading from the expression of an imaging need and project initiation to a clinically usable imaging agent. The definition of the project rationale, the design and optimization of early leads, and the assessment of the imaging potential of an imaging agent candidate are followed by preclinical and clinical development activities that differ from those required for therapeutic agents. These include radiolabeling with a positron emitter and first-in-human clinical studies, to rapidly evaluate the ability of a new imaging agent to address the questions it was designed to ans...
Source: ChemMedChem - April 18, 2024 Category: Chemistry Authors: Lian Xue Caitlin V M L Jie Sandrine Desrayaud Yves P Auberson Source Type: research
Recent Development of Transition Metal Complexes as Chemotherapeutic Hypoxia Activated Prodrug (HAP)
ChemMedChem. 2024 Apr 18:e202400127. doi: 10.1002/cmdc.202400127. Online ahead of print.ABSTRACTHypoxia is a state characterized by low concentration of Oxygen. Hypoxic state is often found in the central region of solid tumors. Hypoxia is associated with abnormal neovascularization resulted in poor blood flow in tissues and increased proliferation of tumor cells, imbalance between O2 supply and O2 consumption in tumor cells, high concentration of proton and strong reducibility. And, these abnormalities enhance the survival potency of the hypoxic tumours and increase the resistance towards chemotherapy and radiotherapy. On...
Source: ChemMedChem - April 18, 2024 Category: Chemistry Authors: K Jagathesan Sovan Roy Source Type: research
Developing Low Molecular Weight PET and SPECT Imaging Agents
This article describes the general development path leading from the expression of an imaging need and project initiation to a clinically usable imaging agent. The definition of the project rationale, the design and optimization of early leads, and the assessment of the imaging potential of an imaging agent candidate are followed by preclinical and clinical development activities that differ from those required for therapeutic agents. These include radiolabeling with a positron emitter and first-in-human clinical studies, to rapidly evaluate the ability of a new imaging agent to address the questions it was designed to ans...
Source: ChemMedChem - April 18, 2024 Category: Chemistry Authors: Lian Xue Caitlin V M L Jie Sandrine Desrayaud Yves P Auberson Source Type: research
Russell Mechanism-Mediated Cancer Therapy: A Minireview
ChemMedChem. 2024 Apr 16:e202400186. doi: 10.1002/cmdc.202400186. Online ahead of print.ABSTRACTThe Russell mechanism, proposed by Russell, is a cyclic mechanism for the formation of linear tetroxide intermediates, which can spontaneously produce cytotoxic singlet oxygen (1O2) independent of oxygen, suggesting its anticancer potential. Compared with other mainstream anticancer strategies, the Russell mechanism employed for killing cancer cells does not require external energy input, harsh pH condition, and sufficient oxygen. However, up till now, the applications of Russell mechanism in antitumor therapy have been relative...
Source: ChemMedChem - April 17, 2024 Category: Chemistry Authors: Rufeng Zhang Xiaoyang Liu Fu-Gen Wu Source Type: research
Esterification of Cyclic N6-threonylcarbamoyladenosine during RNA Sample Preparation
ChemMedChem. 2024 Apr 17:e202400115. doi: 10.1002/cmdc.202400115. Online ahead of print.ABSTRACTThe continuous deciphering of crucial biological roles of RNA modifications and their involvement in various pathological conditions, together with their key roles in the use of RNA-based therapeutics, has reignited interest in studying the occurrence and identity of non-canonical ribonucleoside structures during the past years. Discovery and structural elucidation of new modified structures is usually achieved by combination of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) at the nucleoside level and stab...
Source: ChemMedChem - April 17, 2024 Category: Chemistry Authors: Larissa Bessler Jason Sirleaf Christopher J Kampf Katarzyna Frankowska Gra żyna Leszczyńska Till Opatz Mark Helm Source Type: research
Structure and Activity of Reconstructed Pseudo-Ancestral Cyclotides
ChemMedChem. 2024 Apr 17:e202400124. doi: 10.1002/cmdc.202400124. Online ahead of print.ABSTRACTCyclotides are cyclic peptides that are promising scaffolds for the design of drug candidates and chemical tools. However, despite there being hundreds of reported cyclotides, drug design studies have commonly focussed on a select few prototypic examples. Here, we explored whether ancestral sequence reconstruction could be used to generate new cyclotides for further optimization. We show that the reconstructed 'pseudo-ancestral' sequences, named Ancy-m (for the ancestral cyclotide of the Möbius sub-family) and Ancy-b (for the b...
Source: ChemMedChem - April 17, 2024 Category: Chemistry Authors: Zhihao Jiang Yen-Hua Huang Quentin Kaas David J Craik Conan K Wang Source Type: research
Surface functionalized titanium nitride electrode for CMOS compatible bioelectronic devices
In this study, a surface functionalization approach by covalent grafting of an organic thin film containing hydroxyl groups on TiN surface via electroreduction of diazonium salts "4-(2-hydroxyethyl)benzenediazonium salt" is presented. Cyclic voltammetry procedures were carried out at the potential ranges of -0.8 V~0.5 V (vs Ag/AgCl) with varying numbers of potential cycles (i.e., 5, 25, and 50 cycles) in order to study the thickness of modification layer. Then, the electrochemical properties, surface morphology, and chemical structures of the sample before and after modifications were investigated via multiple characteriza...
Source: ChemMedChem - April 17, 2024 Category: Chemistry Authors: Meng Yu Xiaohui Tang Shijia Yang Zhenhua Li Chang Chen Sijia Xie Source Type: research
Russell Mechanism-Mediated Cancer Therapy: A Minireview
ChemMedChem. 2024 Apr 16:e202400186. doi: 10.1002/cmdc.202400186. Online ahead of print.ABSTRACTThe Russell mechanism, proposed by Russell, is a cyclic mechanism for the formation of linear tetroxide intermediates, which can spontaneously produce cytotoxic singlet oxygen (1O2) independent of oxygen, suggesting its anticancer potential. Compared with other mainstream anticancer strategies, the Russell mechanism employed for killing cancer cells does not require external energy input, harsh pH condition, and sufficient oxygen. However, up till now, the applications of Russell mechanism in antitumor therapy have been relative...
Source: ChemMedChem - April 17, 2024 Category: Chemistry Authors: Rufeng Zhang Xiaoyang Liu Fu-Gen Wu Source Type: research
Nucleic Acid Materials-mediated Innate Immune Activation for Cancer Immunotherapy
ChemMedChem. 2024 Apr 15:e202400111. doi: 10.1002/cmdc.202400111. Online ahead of print.ABSTRACTAbnormally localized nucleic acids (NAs) are considered as pathogen associated molecular patterns (PAMPs) in innate immunity. They are recognized by NAs-specific pattern recognition receptors (PRRs), leading to the activation of associated signaling pathways and subsequent production of type I interferons (IFNs) and pro-inflammatory cytokines, which further trigger the adaptive immunity. Notably, NAs-mediated innate immune activation is highly dependent on the conformation changes, especially the aggregation of PRRs. Evidence in...
Source: ChemMedChem - April 16, 2024 Category: Chemistry Authors: Xinyu Xu Yuxuan Hong Huanhuan Fan Zijian Guo Source Type: research
Chemists Invent Drugs and Drugs Save Lives
ChemMedChem. 2024 Apr 14:e202400074. doi: 10.1002/cmdc.202400074. Online ahead of print.ABSTRACTDrug molecules are the centrepiece of modern medical therapies, providing relief from pain, combatting infections and providing a myriad of other therapeutic effects. The quest for new and improved drug molecules drives medical research, and the introduction of a new drug frequently becomes a newsworthy event capturing the attention of the press and general public. And yet, misconceptions abound. Often, the general public thinks that drug molecules are designed, created, and invented by physicians rather than chemists - a misund...
Source: ChemMedChem - April 15, 2024 Category: Chemistry Authors: Donald F Weaver Source Type: research
Discovery and in vitro Evaluation of Novel Serotonin 5-HT2A Receptor Ligands Identified Through Virtual Screening
ChemMedChem. 2024 Apr 15:e202400080. doi: 10.1002/cmdc.202400080. Online ahead of print.ABSTRACTThe 5-HT2A receptor is a molecular target of high pharmacological importance. Ligands of this protein, particularly atypical antipsychotics, are useful in the treatment of numerous mental disorders, including schizophrenia and major depressive disorder. Structure-based virtual screening using a 5-HT2A receptor complex was performed to identify novel ligands for the 5-HT2A receptor, serving as potential antidepressants. From the Enamine screening library, containing over 4 million compounds, 48 molecules were selected for subsequ...
Source: ChemMedChem - April 15, 2024 Category: Chemistry Authors: Agata Zi ęba Damian Bartuzi Piotr St ępnicki Dariusz Matosiuk Tomasz M Wr óbel Tuomo Laitinen Mari án Castro Agnieszka Anna Kaczor Source Type: research
