Related Experiment Video
Updated: Aug 10, 2026
12:02
Assays for the Identification of Novel Antivirals against Bluetongue Virus
Published on: October 11, 2013
Clavines. New antibiotics with cytostatic activity
Biochemical Pharmacology
|February 15, 1984
Summary
Certain clavines, including agroclavine and its derivatives, exhibit potent cytostatic activity by inhibiting DNA synthesis in mouse lymphoma cells. This effect was reversible at lower concentrations, suggesting potential therapeutic applications.
Area of Science:
- Pharmacology
- Biochemistry
- Cell Biology
Background:
- Ergolines are a class of compounds with diverse biological activities.
- Understanding the cytostatic potential of ergoline derivatives is crucial for drug discovery.
- The L5178y mouse lymphoma cell system is a standard model for evaluating cytotoxic agents.
Purpose of the Study:
- To determine the cytostatic potentials of ten ergoline compounds.
- To investigate the mechanism of action of active ergolines.
- To compare the activity of clavines and lysergic acid derivatives.
Main Methods:
- Cytostatic activity was assessed using the L5178y mouse lymphoma cell system.
- Dose-response curves were generated to determine ED50 values.
- Incorporation studies and assessment of cellular growth were performed to elucidate the mechanism of action.
Main Results:
- Agroclavine, 1-propyl-agroclavine, 1-propyl-festuclavine, and 1-allyl-festuclavine demonstrated potent cytostatic effects (ED50: 3.5-4.3 microM).
- The inhibitory effect of these clavines was reversible at concentrations up to 2x ED50.
- Evidence suggests these compounds inhibit DNA synthesis, leading to unbalanced cell growth.
Conclusions:
- Specific clavine derivatives possess significant cytostatic properties.
- Inhibition of DNA synthesis appears to be the primary mechanism of action.
- Lysergic acid derivatives and 1-hydroxymethyl-festuclavine showed no detectable cytostatic activity in this system.
Related Concept Videos
01:10Drugs that Destabilize Microtubules
Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
01:16Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
Helicobacter pylori, a resilient gram-negative bacterium, can thrive in the stomach's harsh, acidic environment. Infection with H. pylori leads to a cascade of events within the stomach lining. One of the critical disruptions caused by this bacterium is the interference with somatostatin production, a hormone responsible for regulating acid secretion. This interference tips the balance, escalating acid secretion and diminishing bicarbonate levels. This imbalance compromises the defensive...
01:28Antimicrobial Effectiveness
The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
01:23Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
01:22Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
01:15Antifungal Agents
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...