Related Experiment Video
Updated: Sep 6, 2025
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Dihydropyrazole-Carbohydrazide Derivatives with Dual Activity as Antioxidant and Anti-Proliferative Drugs on Breast
Irving Balbuena-Rebolledo1,2,3, Astrid M Rivera-Antonio1,2, Yudibeth Sixto-López3,4
1Laboratorio de Química Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Avenida Acueducto s/n, Barrio la Laguna Ticomán, Ciudad de México 07340, Mexico.
Abstract:
Breast cancer (BC) is the most frequently diagnosed cancer and is the second-most common cause of death in women worldwide. Because of this, the search for new drugs and targeted therapy to treat BC is an urgent and global need. Histone deacetylase 6 (HDAC6) is a promising anti-BC drug target associated with its development and progression. In the present work, the design and synthesis of a new family of dihydropyrazole-carbohydrazide derivatives (DPCH) derivatives focused on HDAC6 inhibitory activity is presented. Computational chemistry approaches were employed to rationalize the design and evaluate their physicochemical and toxic-biological properties. The new family of nine DPCH was synthesized and characterized. Compounds exhibited optimal physicochemical and toxicobiological properties for potential application as drugs to be used in humans. The in silico studies showed that compounds with -Br, -Cl, and -OH substituents had good affinity with the catalytic domain 2 of HDAC6 like the reference compounds. Nine DPCH derivatives were assayed on MCF-7 and MDA-MB-231 BC cell lines, showing antiproliferative activity with IC50 at μM range. Compound 2b showed, in vitro, an IC50 value of 12 ± 3 µM on human HDAC6. The antioxidant activity of DPCH derivatives showed that all the compounds exhibit antioxidant activity similar to that of ascorbic acid. In conclusion, the DPCH derivatives are promising drugs with therapeutic potential for the epigenetic treatment of BC, with low cytotoxicity towards healthy cells and important antioxidant activity.
Insights
New dihydropyrazole-carbohydrazide derivatives show promise as breast cancer drugs. These compounds inhibit HDAC6, possess antioxidant properties, and exhibit low toxicity to healthy cells.
Area of Science:
- Oncology
- Medicinal Chemistry
- Epigenetics
Background:
- Breast cancer (BC) remains a leading cause of cancer-related death globally, necessitating novel therapeutic strategies.
- Histone deacetylase 6 (HDAC6) is implicated in BC progression, making it a viable drug target.
- Targeted therapies are crucial for improving BC treatment outcomes.
Purpose of the Study:
- To design, synthesize, and evaluate a new series of dihydropyrazole-carbohydrazide (DPCH) derivatives as potential HDAC6 inhibitors for breast cancer treatment.
- To assess the in silico, in vitro antiproliferative, and antioxidant activities of the synthesized DPCH compounds.
- To determine the drug-likeness and safety profile of these novel compounds.
Main Methods:
- Computational chemistry was utilized for rational drug design and property prediction.
- Nine DPCH derivatives were synthesized and characterized using standard chemical techniques.
- In vitro assays were performed to evaluate antiproliferative activity against BC cell lines (MCF-7, MDA-MB-231), HDAC6 inhibition, and antioxidant capacity.
Main Results:
- DPCH derivatives demonstrated favorable physicochemical and toxicobiological properties.
- In silico analysis indicated good binding affinity of certain substituted DPCH compounds to the HDAC6 catalytic domain 2.
- All nine DPCH derivatives exhibited antiproliferative activity against BC cell lines, with IC50 values in the micromolar range. Compound 2b showed an IC50 of 12 ± 3 µM against human HDAC6.
- Compounds displayed significant antioxidant activity comparable to ascorbic acid and low cytotoxicity towards healthy cells.
Conclusions:
- DPCH derivatives represent a promising class of compounds for the epigenetic treatment of breast cancer.
- These novel agents possess therapeutic potential due to their HDAC6 inhibitory activity, antioxidant properties, and favorable safety profile.
- Further investigation into DPCH derivatives could lead to the development of effective and safe breast cancer therapies.
Related Concept Videos
02:34Inhibition of Cdk Activity
01:10Drugs that Destabilize Microtubules
01:15Drugs that Stabilize Microtubules
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:15M-Cdk Drives Transition Into Mitosis
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
01:46Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...