HDAC6 detector: online application for evaluating compounds as potential histone deacetylase 6 inhibitors

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Biochemistry

Background:

• Histone deacetylase 6 (HDAC6) is crucial in cellular processes like division and apoptosis.
• HDAC6 inhibitors are promising therapeutic agents for various diseases.
• Developing effective HDAC6 inhibitors requires robust predictive models.

Purpose of the Study:

• To develop and validate quantitative structure-activity relationship (QSAR) models for HDAC6 inhibitors.
• To create an accessible web application, HDAC6 Detector, for virtual screening of potential HDAC6 inhibitors.
• To evaluate novel hydroxamic acid derivatives as potential HDAC6 inhibitors.

Main Methods:

• Development of QSAR models for HDAC6 inhibitors.
• Integration of QSAR models into the HDAC6 Detector web application.
• Virtual screening of novel hydroxamic acid derivatives using the HDAC6 Detector.
• In vitro evaluation of inhibitory activity against HDAC6.

Main Results:

• The HDAC6 Detector application was developed, incorporating QSAR models and Lipinski's rule compliance checks.
• Virtual screening identified promising HDAC6 inhibitor candidates from a series of novel hydroxamic acids.
• Compounds V-6 and V-11 demonstrated potent in vitro inhibitory activity with IC50 values of 0.99 nM and 0.81 nM, respectively.

Conclusions:

• The developed QSAR models and the HDAC6 Detector application are effective tools for identifying potential HDAC6 inhibitors.
• Novel hydroxamic acid derivatives, particularly V-6 and V-11, show significant promise as therapeutic agents targeting HDAC6.