A new series of nitro analogues of the duocarmycins was prepared and evaluated for hypoxia-selective anticancer activity. The compounds incorporate 13 different amine-containing side chains designed to bind in the minor groove of DNA while spanning a wide range of base strength from pK 9.64 to 5.24. The most favorable in vitro properties were associated with strongly basic side chains, but the greatest in vivo antitumor activity was found for compounds containing a weakly basic morpholine. This applies to single-agent activity and for activity in combination with irradiation or chemotherapy (gemcitabine or docetaxel). In combination with a single dose of γ irradiation 50 at 42 μmol/kg eliminated detectable clonogens in some SiHa cervical carcinoma xenografts, and in combination with gemcitabine using a well-tolerated multidose schedule, the same compound caused regression of all treated A2780 ovarian tumor xenografts. In the latter experiment, three of seven animals receiving the combination treatment were completely tumor free at day 100.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.7b00563 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Premovement neuronal activity in the primary motor cortex is associated with the initiation of ipsilateral hand movements in monkeys.
Neurosci Res
January 2025
Neural Prosthetics Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan.
The primary motor cortex (M1) is believed to be a cortical center for the execution of limb movements. Although M1 neurons mainly project to the spinal cord on the contralateral side, some M1 neurons project to the ipsilateral side via the uncrossed corticospinal pathway. Moreover, some M1 neurons are activated during ipsilateral forelimb movements.
View Article and Find Full Text PDFBrassinin from Brassica campestris L. inhibits colorectal cancer by inducing p62/NRF2/GPX4-regulated ferroptosis.
Animal Model Exp Med
January 2025
College of Traditional Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine, Taiyuan, China.
Background: Indole phytoalexins, plant-derived compounds present in cruciferous vegetables, have demonstrated anticancer properties. Brassinin (BSN), derived from Brassica campestris L. var.
View Article and Find Full Text PDFCD4-Derived Double-Negative T Cells Ameliorate Alzheimer's Disease-Like Phenotypes in the 5×FAD Mouse Model.
CNS Neurosci Ther
January 2025
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Background: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder that is difficult to predict and is typically diagnosed only after symptoms manifest. Recently, CD4 T cell-derived double-negative T (DNT) cells have shown strong immuno-regulatory properties in both in vitro and in vivo neuronal inflammation studies. However, the effectiveness of DNT cells in treating on AD are not yet fully understood.
View Article and Find Full Text PDFLentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice.
AMB Express
January 2025
Department of Biotechnology, College of Basic Medical Science, Dalian Medical University, Dalian, 116044, China.
Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted.
View Article and Find Full Text PDFMolecular and cellular morphology of placenta unveils new mechanisms of reproductive immunology.
J Adv Res
January 2025
Jinxin Research Institute for Reproductive Medicine and Genetics, Sichuan Jinxin Xi'nan Women's and Children's Hospital, Chengdu, China; Provincial Key Laboratory of Molecular Pathology and Personalized Medicine, Center of Collaborative and Creative Center, Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou, China. Electronic address:
Introduction: Despite of numerous studies of the placenta, some molecular and cellular characteristics, particularly the relationship among different cell types, have not been well understood. We aim to investigate the basic and intricate details of cellular and molecular elements in early and late phase placentas to gain better understanding of the immune regulation of human reproductive process.
Methods: A novel combination of techniques of spatial transcriptomics(ST), multiple immunohistochemistry, and a dual labeling combining immunohistochemistry and (fluorescence in situ hybridization) FISH on normal and ectopic pregnancy and animal models was employed to investigate the placenta at tissue, cell, protein and molecular levels and to trace the fetal and maternal origin of every cell in early and late placentas.
Want 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!