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MOLECULAR DOCKING STUDY AND ADME/T PREDICTIONS OF 2 PHENYLAMINOIMIDAZO[4,5-H]ISOQUINOLIN-9-ONES WITH POTENT ANTI-AROMATASE CYTOCHROME P450 ACTIVITY IN BREAST CANCER THERAPY

 

George Oche Ambrose1,2

  1. Department of Biochemistry University of Ilorin, Ilorin Nigeria
  2. Ben Carson School of Medicine, Ileshan-Remo, Nigeria

 

Abstract

Aim

This study is aimed at examining 2 phenylaminoimidazo[4,5-h]isoquinolin-9-ones for their inhibitory activities against aromatase cytochrome p450 in breast cancer therapy via molecular docking approach and to evaluate their drug-likeness properties and ADME/T predictions.

Background

Post-menopausal women with hormone dependent Breast cancer in the past were treated with tamoxifen, which mediates its action by blocking estrogen binding to the estrogen receptor thereby preventing estrogen induced proliferation. Unfortunately, tamoxifen is a partial agonist in many tissue types. Alternatively, aromatase inhibitors represent the first successful class of cancer therapeutics by inhibiting estrogen synthesis. However, recent studies have shown that the first, second and third generation of aromatase inhibitors although potent yet present with adverse reactions such as nausea, abdominal pain, baldness, joint pain, diarrhea, vaginal dryness e.t.c

Methods

Computational docking analysis was performed using PyRx, AutoDock Vina option based on scoring functions and the target was validated so as to ensure that the right target was used for this analysis. Phyto-chemical properties of 2 phenylaminoimidazo[4,5-h]isoquinolin-9-ones were determined by using virtual tool, ADMETlab server (http://admet.scbdd.com/) .

 

Results

Docking study by PyRx tools reveals that 17 out of 30 of the 2 phenylaminoimidazo[4,5-h]isoquinolin-9-ones compounds showed stable binding complex with higher binding affinity values when compared with the co-crystallized ligand (reference compound). However, only 5 of these compounds (CHEMBL26409, CHEMBL26864, CHEMBL2799, CHEMBL27302 and CHEMBL27485) satisfy the ADME/T predictions and the drug-likeness according to the lipinsky rule.

 

Conclusions

These five (5) compounds may be better drug candidates for breast cancer which can be explored on further studies.

 

 

Name of Presenter: George Oche Ambrose

Title: Mr.

Affiliations:

  1. Department of Biochemistry University of Ilorin, Ilorin Nigeria
  2. Ben Carson School of Medicine, Ileshan-Remo, Nigeria

 

 

 

 

 

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