Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Metabolically programmed polyamine analogue antidiarrheals

R J Bergeron1, G W Yao, H Yao

  • 1Department of Medicinal Chemistry, University of Florida, Gainesville 32610, USA.

Journal of Medicinal Chemistry
|June 21, 1996
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Advance in the study on p38 MAPK mediated drug resistance in leukemia.

European review for medical and pharmacological sciences·2016
Same author

Monoacylglycerol lipase inhibitors produce pro- or antidepressant responses via hippocampal CA1 GABAergic synapses.

Molecular psychiatry·2016
Same author

Green Light-emitting Diodes Light Stimuli during Incubation Enhances Posthatch Growth without Disrupting Normal Eye Development of Broiler Embryos and Hatchlings.

Asian-Australasian journal of animal sciences·2016
Same author

[A patient with serious sinusal malformation].

Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery·2016
Same author

CD47: a potential immunotherapy target for eliminating cancer cells.

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·2016
Same author

Mesenchymal stem cells and immunomodulation: current status and future prospects.

Cell death & disease·2016
Same journal

Discovery of Effective Dual PROTAC Degraders with Synergistic Antitumor Activity for Overcoming Tamoxifen-Resistant Breast Cancer.

Journal of medicinal chemistry·2026
Same journal

In Silico ADMET: From Current Practices to Novel Profilers.

Journal of medicinal chemistry·2026
Same journal

A Zirconium Aza-BODIPY Derivative as a Near-Infrared Fluorescent/Photoacoustic Imaging Bimodal Probe.

Journal of medicinal chemistry·2026
Same journal

Landscaping the Nitazene Scaffold to Identify Novel Mu-Opioid Receptor Modulators: From Molecular Design and Chemical Synthesis to Pharmacological Profiling.

Journal of medicinal chemistry·2026
Same journal

Development of Indole-3-yl-methylene-thiobarbital Derivatives as Inhibitors of HDAC8 Enzyme Activity.

Journal of medicinal chemistry·2026
Same journal

Discovery of a Potent NAMPT-Targeting PROTAC for the Suppression of Triple-Negative Breast Cancer via Macrophage Reprogramming.

Journal of medicinal chemistry·2026
See all related articles

Researchers developed a new antidiarrheal drug, (HO)2-DEHSPM, which is less toxic and does not accumulate in tissues like its predecessor, DEHSPM. This novel tetraamine analogue effectively prevents diarrhea while improving safety profiles for antidiarrheal drug development.

Area of Science:

  • Pharmacology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Antidiarrheal drug development faces challenges with toxicity and metabolic stability.
  • N1,N14-diethylhomospermine (DEHSPM) shows efficacy but exhibits chronic toxicity due to metabolite accumulation.

Purpose of the Study:

  • To design and synthesize a metabolically labile analogue of DEHSPM with retained antidiarrheal properties.
  • To reduce the chronic toxicity associated with DEHSPM's persistent metabolite.

Main Methods:

  • Introduction of hydroxyl groups into DEHSPM to create N1,N14-diethyl-(3R),(12R)-dihydroxyhomospermine [(HO)2-DEHSPM].
  • Utilized molecular modeling to predict drug-target interactions.
  • Assessed antidiarrheal efficacy, tissue distribution, metabolic stability, and toxicity in rodent models.

Related Experiment Videos

Main Results:

  • [(HO)2-DEHSPM] demonstrated identical biological properties to DEHSPM, including polyamine transport inhibition and anti-cancer activity.
  • Chronic administration of [(HO)2-DEHSPM] showed no significant metabolite accumulation in tissues.
  • [(HO)2-DEHSPM] exhibited 3-fold lower toxicity compared to DEHSPM.
  • Both drugs completely prevented diarrhea in a castor oil-induced rat model at 5 mg/kg.

Conclusions:

  • [(HO)2-DEHSPM] represents a promising antidiarrheal agent with an improved safety profile.
  • Metabolic lability can be engineered into drug candidates to mitigate toxicity.
  • This tetraamine analogue offers a viable alternative for antidiarrheal therapy.