Richa, Meenakshi Sharma, Monika, Renu Chadha and Neelima Dhingra*
Department of Pharmaceutical Chemistry, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
*Corresponding Author: Neelima Dhingra, Assistant Professor Department of Pharmaceutical Chemistry, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Received: December 27, 2017; Published: January 18, 2018
Citation: Neelima Dhingra., et al. “Characterization and Predictive QSAR Analysis of Azasteroids as Five Alpha Reductase Inhibitors”. Acta Scientific Pharmaceutical Sciences 2.2 (2018).
Background and Objective: Major circulating hormone dihydrotestosterone (DHT) is responsible for the development and progression of benign prostate hyperplasia (BPH). The enzyme 5α-reductase (5alpha R) catalyses the reduction of testosterone (T) into the more potent androgen dihydrotestosterone (DHT). Inhibition of 5α-Reductase enzyme is the novel approach for treatment of BPH.
Method: Present work describes synthesis of 17-Oxo-17a-aza-D-homo-5-androsten-3β-yl 4-nitrobenzoate (7), 17-oxo-17a-aza-d-homo-5-androsten-3β-yl 4-aminobenzoate (8) as 5α-reductase inhibitors and their structural characterization using spectral, DSC and PXRD techniques. Preliminary physicochemical properties solubility, dissolution rates, pKa and permeability (log P) has also been determined.
Conclusion: The statistically validated two-dimensional quantitative structure activity relationship (2D QSAR) model was obtained using structurally related 3β-substituted esters of 17a-Aza, 17-oximino, 17-oxo androstane derivatives, through partial least squares (PLS) analysis method of stepwise forward-backward approach. Statistical data of Model 1 (r2 = 0.833, q2 = 0.671; F = 37.498, pred r2= 0.736) correlated with human 5α-reductase inhibitory activity. Validation was done with LOO method. Four descriptors showing positive and negative correlation with the 5α-Reductase inhibitory activity have been included in the model. Physicochemical characterization and statistically correlated model with 5α-reductase activity has not only added to the bank information of the synthesized highly significant molecules, but has also provided a overview of their bioperformance, and facilitated decision making during lead optimization.
Keywords: BPH; 5α-Reductase Inhibitors; Steroidal lactams; DSC; Log P; 2D-QSAR
Copyright: © 2018 Neelima Dhingra., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.