Drug Likeness Screening and Evaluation of Physicochemical Properties of Selected Medicinal Agents by Computer Aided Drug Design Tools
Ganesh H. Sampat, Shailendra S. Suryawanshi, Mahesh Palled, Archana S. Patil, Pukar Khanal, Abhijeet S. Salokhe
Abstract
The current drug research techniques, combinatorial synthesis and high throughput screening, help in obtaining and pre-evaluating thousands of compounds in a short duration of time. Among the selected compounds, the best hit molecule becomes the lead, and the drug likeness property helps to optimize the selection. Lipinski's Rule of five is the most widely used filter in pre-evaluation of compounds, according to Lipinski's Rule of five the molecule with poor oral absorption and low permeation has the molecular weight >500, ClogP >5, hydrogen bond acceptor more than 10 and hydrogen bond donor more than 5. To evaluate the Rule of Five, the top selling drugs of 2018-19 were selected. Among the selected 56 drugs, 12 drugs (tenofovir disoproxil, sofosbuvir and ledipasvir, sofosbuvir/velpatasvir, trastuzumab, glecaprevir, pegtilgrastion, Lumacaftor/ ivacaftor, fluticasone propionate and salmetarol, elbasvir, darunavir ethanolate, Linagliptin, metformin, fluticasone furoate and vilanterol) did not fulfill the rule. The rule is very useful in selecting the better compound in chemolibraries, but should be used carefully and with certain criterion due to possible exclusion of promising compounds.