Cancer is the second leading cause of death, after cardiovascular diseases. Different strategies have been developed to treat cancer; however, chemotherapy with cytotoxic agents is still the most widely used treatment approach. Nevertheless, drug resistance to available chemotherapeutic agents is still a serious problem, and the development of new active compounds remains a constant need. Taking advantage of the molecular hybridization approach, in the present work we designed, synthesized, and tested the cytotoxic activity of two hybrid compounds and seven derivatives based on the structure of combretastatin A-4 and 2,3-diphenyl-2-indazole. Practical modifications of reported synthetic protocols for 2-pheny-2-indazole and 2,3-dipheny-2-indazole derivatives under microwave irradiation were implemented. The cytotoxicity assays showed that our designed hybrid compounds possess strong activity, especially compound , which resulted even better than the reference drug cisplatin against HeLa and SK-LU-1 cells (IC of 0.16 and 6.63 µM, respectively), and it had similar potency to the reference drug imatinib against K562 cells. Additionally, in silico and in vitro studies strongly suggest tubulin as the molecular target for hybrid compound .
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401203 | PMC |
| http://dx.doi.org/10.3390/ph14080815 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
New cinnamic acid sugar esters as potential UVB filters: Synthesis, cytotoxicity, and physicochemical properties.
Carbohydr Res
January 2025
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Campus Scientifico E. Mattei, via Ca' Le Suore 2, 61029, Urbino, PU, Italy. Electronic address:
Cinnamic Acid Sugar Ester Derivatives (CASEDs) are a class of natural compounds that exhibit several interesting biological activities. However, to date, no examples of their use in sunscreen formulations have been reported. Here, we describe the synthesis of a series of novel cinnamic acid esters of glucose (4a-g), ribose (4h) and lactose (4i) starting from the respective acetals 3.
View Article and Find Full Text PDFPurpose: Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti-PD-1 antibody, in advanced sarcomas.
Methods: BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years.
Design of ROS-Triggered Sesquiterpene Lactone SC Prodrugs as TrxR1 Covalent Inhibitors for the Treatment of Non-Small Cell Lung Cancer.
J Med Chem
January 2025
Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS.
View Article and Find Full Text PDFNovel Strategy of Antibody Affinity Maturation and Enhancement of Nucleolin-Mediated Antibody-Dependent Cellular Cytotoxicity Against Triple-Negative Breast Cancer.
Biotechnol J
January 2025
Faculty of Pharmacy, iMed.ULisboa - Research Institute for Medicines, University of Lisbon, Lisbon, Portugal.
Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer that remains an unmet medical need. Because TNBC cells do not express the most common markers of breast cancers, there is an active search for novel molecular targets in triple-negative tumors. Additionally, this subtype of breast cancer presents strong immunogenic characteristics which have been encouraging the development of immunotherapeutic approaches against the disease.
View Article and Find Full Text PDFImmune-Mediated Liver Injury From Checkpoint Inhibitor: An Evolving Frontier With Emerging Challenges.
Liver Int
February 2025
APHP, Hôpital Paul-Brousse, Centre Hépato-Biliaire, Inserm, Unité 1193, Université Paris-Saclay, FHU Hepatinov, Villejuif, France.
Over the past decade, immune checkpoint inhibitors (ICIs) have transformed the treatment of cancer, though they come with the risk of immune-related adverse (irAEs) events such as hepatotoxicity or Immune-mediated Liver Injury from Checkpoint Inhibitors (ILICI). ILICI is a serious irAE that, when severe, requires cessation of ICI and initiation of immunosuppression. Cytotoxic T Lymphocytes (CTLs) play a central role in ILICI; however, they are just part of the picture as immunotherapy broadly impacts all aspects of the immune microenvironment and can directly and indirectly activate innate and adaptive immune cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!