Related Experiment Video
Updated: Jul 12, 2025
Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Hydroxamic Acids Containing a Bicyclic Pinane Backbone as Epigenetic and Metabolic Regulators: Synergizing Agents to
Yulia Aleksandrova1, Aldar Munkuev2, Evgenii Mozhaitsev2
1Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Severnij Pr. 1, 142432 Chernogolovka, Russia.
Abstract:
Multidrug resistance is the dominant obstacle to effective chemotherapy for malignant neoplasms. It is well known that neoplastic cells use a wide range of adaptive mechanisms to form and maintain resistance against antitumor agents, which makes it urgent to identify promising therapies to solve this problem. Hydroxamic acids are biologically active compounds and in recent years have been actively considered to be potentially promising drugs of various pharmacological applications. In this paper, we synthesized a number of hydroxamic acids containing a p-substituted cinnamic acid core and bearing bicyclic pinane fragments, including derivatives of (-)-myrtenol, (+)-myrtenol and (-)-nopol, as a Cap-group. Among the synthesized compounds, the most promising hydroxamic acid was identified, containing a fragment of (-)-nopol in the Cap group 18c. This compound synergizes with cisplatin to increase its anticancer effect and overcomes cisplatin resistance, which may be associated with the inhibition of histone deacetylase 1 and glycolytic function. Taken together, our results demonstrate that the use of hydroxamic acids with a bicyclic pinane backbone can be considered to be an effective approach to the eradication of tumor cells and overcoming drug resistance in the treatment of malignant neoplasms.
Insights
New hydroxamic acids combat chemotherapy resistance in cancers. Compound 18c, featuring a bicyclic pinane, synergizes with cisplatin, inhibiting histone deacetylase 1 and glycolysis to eradicate tumor cells.
Area of Science:
- Medicinal Chemistry
- Oncology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, necessitating novel therapeutic strategies.
- Neoplastic cells employ diverse mechanisms to resist antitumor agents, highlighting the urgent need for effective solutions.
- Hydroxamic acids are a class of biologically active compounds with potential pharmacological applications.
Purpose of the Study:
- To synthesize novel hydroxamic acids incorporating a p-substituted cinnamic acid core and bicyclic pinane fragments.
- To identify compounds that can overcome multidrug resistance in cancer.
- To evaluate the synergistic effects of these compounds with existing chemotherapies like cisplatin.
Main Methods:
- Synthesis of hydroxamic acids derived from (-)-myrtenol, (+)-myrtenol, and (-)-nopol.
- Anticancer efficacy testing of synthesized compounds.
- Assessment of synergistic effects with cisplatin.
- Investigation of potential mechanisms of action, including histone deacetylase 1 and glycolytic function inhibition.
Main Results:
- Several hydroxamic acids with bicyclic pinane fragments were successfully synthesized.
- Compound 18c, containing a (-)-nopol-derived cap group, demonstrated significant promise.
- Compound 18c synergized with cisplatin, enhancing its anticancer effect and overcoming cisplatin resistance.
- Inhibition of histone deacetylase 1 and glycolytic function was implicated in the observed effects of compound 18c.
Conclusions:
- Hydroxamic acids with bicyclic pinane backbones represent a promising therapeutic approach for cancer treatment.
- Compound 18c shows potential for eradicating tumor cells and overcoming drug resistance in malignant neoplasms.
- Targeting histone deacetylase 1 and glycolytic pathways may be key mechanisms for overcoming MDR.
Related Concept Videos
02:56Treatment Resistant Cancers
01:27Combined Effects of Drugs: Synergism
Such synergistic combinations...
01:15Drugs that Stabilize Microtubules
01:10Drugs that Destabilize Microtubules