Identification of prodigious and under-privileged structural features for RG7834 analogs as Hepatitis B virus expression inhibitor
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In the present work, QSAR (quantitative structure−activity relationship) analysis has been executed for RG7834 analogs. RG7834 is a first-in-class selective and orally available dihydroquinolizinone (DHQ)-based small molecule Hepatitis B virus expression inhibitor. OECD’s guidelines have been followed for developing multiple QSAR models for Hepatitis B virus expression inhibitory activity of 73 RG7834 analogs. The present multiple QSAR models are not only easily interpretable but possess high external predictive ability, as well. These are effective in the recognition of many privileged and underprivileged molecular descriptors, which could be very valuable for the use of these models by the experts and nonexperts of QSAR in future optimizations. The models satisfy threshold values for many fitting, internal and external validation parameters, such as R2 = 0.83, Q2 = 0.80, CCCext = 0.88, etc., thereby demonstrating good external predictive ability of the models. The multiple QSAR and pharmacophoric models successfully identified a good number of important positively and negatively related structural features of RG7834 analogs that govern their Hepatitis B virus expression inhibitory activity. The results could be very beneficial to synthetic/medicinal chemists for future alterations of RG7834 analogs as better drug candidates.
KeywordsRG7834 analogs Hepatitis B virus Dihydroquinolizinone QSAR Pharmacophore modeling
Hepatitis B virus
Multiple linear regression
Quantitative structure−activity analysis
World Health Organization
Absorption, Distribution, Metabolism, Excretion and Toxicity
Ordinary least square
Organisation for Economic Cooperation and Development
Objective feature selection
Subjective feature selection
The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research (Group No. RG-1435-083). Authors are grateful to Dr. Paola Gramatica and QSARINS-Chem developing team for providing QSARINS-Chem 2.2.2.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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