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Published on:November 2018
Indian Journal of Pharmaceutical Education and Research, 2018; 52(4s2):S296-S302
Original Article | doi:10.5530/ijper.52.4s.110

Pharmacophore and Atom Based 3D QSAR Studies on the Novel 5-Alpha-Reductase Inhibitors


Authors and affiliation (s):

Abhishek Shah1, Richard Lobo1*, Nandakumar Krishnadas2, Aravinda Pai3

1Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy for Higher Education, Manipal - 576104, Karnataka, INDIA.

2Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy for Higher Education, Manipal - 576104, Karnataka, INDIA.

3Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy for Higher Education, Manipal - 576104, Karnataka, INDIA.

Abstract:

Aim/Background: The anomalous production of dihydrotestosterone (DHT) observed in benign prostatic hyperplasia and prostate cancer particularly in tissues of the prostate gland. The primary male sex hormone, testosterone (T) is improved to a metabolite in cells by 5a-reductase (5aR) type II enzyme through NADPH. A metabolite is DHT which is more potent than T. Drug therapy is the best alternative for the treatment of benign prostatic hyperplasia (BPH). Drug therapy act by dropping the DHT formation through inhibiting the 5aR enzyme. Thus, this research work was undertaken to design a novel 5aR enzyme inhibitor by pharmacophore and Atom-based 3D QSAR technique. Materials and Methods: A dataset of twenty-nine ligands available with IC 50 chosen from the literature. Schrodinger molecular modelling software is having, phase 3.0 module implicated for generation of pharmacophore models. Results: Pharmacophore hypothesis with five features having two H-bond acceptors and three hydrophobic group was developed, i.e., AAHHH.715. This Pharmacophore hypothesis regarded as the finest one. This hypothesis resulted into statistically significant three-dimensional QSAR model. The statistical parameters were found to be 0.9804 as r2 value and 0.8321as q2 value. Out of 29 ligands, 23 ligands assigned as training set and 6 ligands as a test set. The squared correlation coefficient between training and test sets based on actual and predicted values were observed to be 0.96 and 0.87 respectively. Conclusion: The 5aR enzyme inhibitors predicting requirements can be done by this built model.

Key words: 5-alpha reductase, Pharmacophore, QSAR, DHT, BPH.

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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