Prediction of structure-Pharmacokinetic-toxicity relationship of a new indol alkaloid isolated from stembark of Strychnos johnsonii (Loganiaceae)

Abstract

Introduction: Drug development is an expensive, difficult and sometimes inefficient process. However, the constraints related to this process tend to be reduced in the early stages of drug development. Indeed, computational approaches have been developed
and guide researchers towards the most active and best tolerated molecules as well as the most suitable dosage forms and drug uses. In this work, we used these computational approaches to predict the structure-pharmacokinetic-galenic pharmacy relationships of a compound isolated from a Cameroonian medicinal plant.

Material and method: A phytochemical study was carried out on the stem barks of Strychnos johnsonii. The structures of the isolated compounds were determined by a complete 1D and 2D NMR spectroscopic analysis and by a comparison with published
data. Then, the descriptors of ADMET parameters of the isolated new compound were predicted by QikProp software.

Results: A new indole alkaloid 10,11-dimethoxy-Na-methyl-β- Carboline (1) and a mixture of known isomers composed of Stigmasterol (2) and β-sistosterol (3) were isolated. The new compound presented complies with Lipinski rules, would be stable to
metabolism and would have urinary elimination and a low probability to induce arrhythmias.

Conclusion: 10,11-dimethoxy-Na-methyl-β- Carboline would have the properties of a good drug candidate.