Abstract
Most of the targeted discoveries in tuberculosis research have covered previously explored chemical structures but neglected physiochemical properties. Until now, no efficient prediction tools have been developed to discriminate the novelty of screened compounds at early stages. To overcome this deficit, a drastic novel approach must include physicochemical properties filters provided by Chemical Global Positioning System-Natural Product analysis (ChemGPS-NP). Three different screening schemes GSK, GVKBio, and NIAID provided 776, 2880, and 3779 compounds respectively and were evaluated based on their physicochemical properties and thereby proposed as deduction examples. Charting the physiochemical property spaces of these sets identified the merits and demerits of each screening scheme by simply observing the distribution over the chemical property space. We found that GSK screening set was confined to a certain space, losing potentially active compounds when compared with an in-house constructed 459 highly active compounds (active set), while the GVKBio and NIAID screening schemes were evenly distributed through space. The latter two sets had the advantage, as they have covered a larger space and presented compounds with additional variety of properties and activities. The in-house active set was cross-validated with MycPermCheck and SmartsFilter to be able to identify priority compounds. The model demonstrated undiscovered spaces when matched with Maybridge drug-like space, providing further potential targets. These undiscovered spaces should be considered in any future investigations. We have included the most active compounds along with permeability and toxicity filters as supplemented material.