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Our group developed a new model of drug combination consisting of the use of antineoplastic drugs and different repurposed drugs, having demonstrated that antimalarial and central nervous system (CNS) drugs have a promising anticancer profile as standalone agents, as well as in combined regimens. Here, we evaluated the anticancer profiles of two different CNS drugs (edaravone and quetiapine), both alone and in combination with antineoplastic agents for breast and colon cancer, to explore whether these repurposed drugs could synergistically enhance the anticancer potential of chemotherapeutic drugs. We also developed a new model of combination using two repurposed drugs, to explore whether this model of combination could also be suitable for application in breast and colon cancer therapy. MCF-7 and HT-29 cancer cells were incubated for 48 h with each individual drug (0.01-100 µM) to determine their IC. Cells were then treated with the IC value for doxorubicin or paclitaxel (MCF-7) or 5-fluorouracil (HT-29) and combined with increasing concentrations of edaravone or quetiapine for 48 h. Both cell lines were also treated with a combination of two antimalarial drugs (mefloquine and pyronaridine) or two CNS drugs (fluphenazine and sertraline) for 48 h. We found that the use of quetiapine in combined therapies seems to synergistically enhance the anticancer activity of doxorubicin for the management of breast cancer. Both CNS drugs significantly improved the cytotoxic potential of 5-fluorouracil in HT-29 cells, with quetiapine synergistically interacting with the antineoplastic drug in this drug combination. Regarding the combination of repurposed drugs, only found one synergic combination regimen (sertraline IC plus variable concentrations of fluphenazine) with anticancer potential against HT-29 colon cancer cells was found. Taken together, these results suggest that quetiapine and edaravone can be used as adjuvant agents in chemotherapy for colon cancer. It was also found that the combination of repurposed drugs, specifically the CNS drugs sertraline and fluphenazine, may have an interesting profile for application in colon cancer novel therapies.
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http://dx.doi.org/10.3390/cimb44100335 | DOI Listing |
NAR Cancer
September 2025
Institute of Pathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Personalized treatment selection is crucial for cancer patients due to the high variability in drug response. While actionable mutations can increasingly inform treatment decisions, most therapies still rely on population-based approaches. Here, we introduce neural interaction explainable AI (NeurixAI), an explainable and highly scalable deep learning framework that models drug-gene interactions and identifies transcriptomic patterns linked with drug response.
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September 2025
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Ghana, Accra, Ghana.
There is a need to improve the discovery of new drugs for neglected tropical diseases (NTDs), as the lack of financial incentives has slowed their development. Currently, ivermectin and moxidectin are used in the management of onchocerciasis. We present a proof-of-concept study based on computational methods to find anti-infectives that can be repurposed or serve as lead compounds for onchocerciasis.
View Article and Find Full Text PDFComput Biol Chem
August 2025
Department of Green Chemistry, National Research Centre, Dokki, P.O. Box 12622, Cairo, Egypt. Electronic address:
This review meticulously examines the development, design, and pharmacological assessment of both well known antiviral and antihypertensive medications all time employing new chemical techniques and structure-based drug design to design and synthesize vital therapeutic entities such as aliskiren (renin inhibitor), captopril (a2-ACE-Inhibitor), dorzolamide (inhibitor of carbonic anhydrase) the review demonstrates initial steps regarding the significance of stereoselective synthesis, metal chelating pharmacophores, and rational molecular properties. More importantly, protease inhibitors (i.e.
View Article and Find Full Text PDFChem Biol Interact
September 2025
College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, 250014, China. Electronic address:
Ferroptosis is an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation and implicated in various human diseases. Despite intensive research, clinically applicable ferroptosis inhibitors remain unavailable. In this study, we identify formoterol, a β-adrenergic agonist widely used to treat asthma and COPD, as a potent and selective ferroptosis inhibitor through scaffold-based screening of FDA-approved drugs.
View Article and Find Full Text PDFInt Immunopharmacol
September 2025
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Center for Research in Inflammatory Diseases, CRID, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address:
Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is associated with impaired neutrophil migration to the infectious focus owing to G protein-coupled receptor kinase (GRK2)-dependent CXCR2 internalization. In the present study, we investigated whether paroxetine, an antidepressant that belongs to the selective serotonin reuptake inhibitor (SSRI) class of drugs and that is also identified as a GRK2 inhibitor, can improve neutrophil recruitment in the cecal ligation and puncture (CLP)-induced sepsis model. Moderate (mCLP) and severe (sCLP) polymicrobial peritonitis were induced in C57BL/6 mice.
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