The Development of a Weighted Index to Optimise Compound Libraries for High Throughput Screening

Abstract

1880 known drugs were collected and analysed for their mainstream molecular descriptors: MW, log P, HA, HD, RB and PSA. The statistical distributions were fitted to Gaussian functions for each of the descriptors. This gave a mathematical tool to calculate a weighted score, or an Index, for each descriptor. Known Drug Indexes (KDIs) were derived either by summation or multiplication of the Indexes, giving one number for each molecule calculated. The KDI summation and multiplication methods give a theoretical maxima of 6 and 1 respectively. According to both methods, methysergide (5.89/0.90), amsacrine (5.89/ 0.89) and fluorometholone (5.88/0.88) have the scores of the most well-balanced pharmaceuticals. The KDIs are advantageous tools in identifying the most well-balanced screening compounds based on the properties of known drugs; the screening collection can be optimised to only include quality compounds, which in turn produce tractable hit and lead compounds from the screening campaign.

The First Berberine-Based Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), an Important DNA Repair Enzyme

“…This method is based on the analysis of drugs in clinical use, i.e., the statistical distribution of each descriptor is fitted to a Gaussian function and normalized to 1 resulting in a weighted index. Both the summation of the indexes (KDI 2a —Equation (1)) and multiplication (KDI 2b —Equation (2)) methods were used [ 39 ]. The numerical results are given in Table S3 in the supplementary information .…”

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

“…The reliability of QikProp is established for the calculated descriptors [46]. The known drug indexes (KDI) were calculated from the molecular descriptors as described by Eurtivong and Reynisson [42].…”

Promising New Inhibitors of Tyrosyl-DNA Phosphodiesterase I (Tdp 1) Combining 4-Arylcoumarin and Monoterpenoid Moieties as Components of Complex Antitumor Therapy

“…The Known Drug Indexes (KDIs) of each ligand were calculated to gauge the balance of the molecular descriptor of the ligands (Table S5, Supplementary Information). This method is based on the statistical analysis of drugs in clinical use (KDS) and a weighted index for each of the six molecular descriptors used; both the summation (KDI 2a ) and multiplication (KDI 2b ) methods were used [73]. The KDI 2a values range from 4.7 to 5.3, with a theoretical maximum of 6 and an average of 4.08 for known drugs.…”