Amlodipine analogs as lead compounds for the discovery of new antibacterial drugs; A chemoinformatics study

The aim of this study was to design and evaluate novel structural analogs of amlodipine that might have similar or higher antibacterial activity than the drug but fewer cardiovascular side effects. A number of computational and data retrieval techniques were used for the investigations in this study. After predicting the bacterial target of amlodipine, 85 structural analogs of the drug were designed and evaluated for their probability of antibacterial activity, calcium channel blocker activity, toxicity profiles, drug-likeness, and pharmacokinetics. Bacterial DNA topoisomerase I was found to be a potential target for amlodipine antibacterial activity, and thirteen analogs of the drug most likely acted on the same bacterial target as amlodipine. Of these analogs, only three had a low probability of acting as calcium channel blockers but an acceptable probability of having low toxicity and drug-likeness properties. However, only two of these analogs with a 1-butyl-4-hydropyridine core showed good probability of pharmacokinetics and are therefore promising as lead compounds for the discovery of new antibacterial drugs.