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image of Design of Novel Acat Inhibitors as Potent Anti-Hyperlipidemic Agents Using Chemometric Approaches

Abstract

Aim

A 2D QSAR study of acyl-coenzyme A (CoA): cholesterol acyltransferase (ACAT) inhibitors revealed that electronic, topological, and steric properties are important structural features required for activity against ACAT.

Background

In order to interpret the evidence encrypted by the molecular structure of the compounds, a standard physicochemical descriptors-centered, and Quantitative Structure-Activity Relationship (QSAR) approach was implemented on a data set of Indoline derivatives were reported to be acyl-coenzyme A (CoA): cholesterol acyltransferase ACAT inhibitors.

Objective

The ACAT enzyme plays an important role in the absorption of dietary cholesterol. Therefore, the inhibition of ACAT is a key strategy or primary objective for the treatment of hypercholesterolemia and atherosclerosis.

Method

Chemo metric models were designed by inserting a battery of statistical techniques in the current study that demonstrate the linear approaches of analysis, including multiple linear regression (MLR), partial least square PLS, and non-linear methods such as artificial neural networks (ANN).

Result

The activity contributions of these molecules were analyzed through regression equation, and the best QSAR model was created with an excellent correlative and predictive ability. Significant statistical values S = 0.35, F = 60.30, r = 0.92, r2 = 0.85, r2 (CV) = 0.82 of the designed models were obtained using stepwise MLR and a comparable PLS and FFNN model with r2 (CV) = 0.82, 0.88 and 0.86 respectively and the relevant descriptors like inertia moment 1 size, Kier Chiv4 (cluster) index, Kier Chiv6(ring) index offered important information regarding this model.

Conclusion

The model reveals that inertia moment 1 size, Kier Chiv4 (cluster) index, and Kier Chiv6 (ring) index are prerequisite descriptors to determine other promising ACAT antagonists with high and liable potency against the target. Therefore, these characteristics may be used efficiently for the design and evaluation of active compounds as new ACAT inhibitors thanks to their utilization.

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2024-12-02
2025-01-24

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Design of Novel Acat Inhibitors as Potent Anti-Hyperlipidemic Agents Using Chemometric Approaches
Bentham Science Publishers ; https://doi.org/10.2174/0115734080320466241003103148
/content/journals/cei/10.2174/0115734080320466241003103148
/content/journals/cei/10.2174/0115734080320466241003103148
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  • Article Type:     Research Article
Keywords: FFNN ; ACAT ; PLS ; MLR ; hypercholesterolemia ; QSAR

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