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In silico study of the mechanism of action, pharmacokinetic and toxicological properties of some N-methylanthranilates and their analogs

Izabel da Silva Hage-Melim, Lorane, Curtolo Poiani, João Gabriel, Tomich de Paula da Silva, Carlos Henrique, Boylan, Fábio
Food and chemical toxicology 2019 v.131 pp. 110556
Choisya ternata, anti-allergic agents, antidepressants, computer simulation, essential oils, in vivo studies, leaves, mechanism of action, pharmacokinetics, prediction, toxicology, tranquilizers
The in silico evaluation for the three previously synthesized compounds (Methyl (MMA), propyl (PMA) and isopropyl (IMA) N-methylanthranilate), MMA and IMA originally found in the leaf essential oil of Choisya ternata, provided a very good confirmation for the in vivo pharmacological results obtained with such compounds for a number of pharmacological targets. This manuscript dealt with their assessment in six pharmacological targets to understanding anti-inflammatory, antinociceptive, anxiolytic, antidepressant and anti-allergic activities using docking molecular as well as their pharmacokinetics and toxicological parameters prediction. The compound IMA seems to be the best one when all the combined parameters are put together. Interestingly this compound presented the best in vivo profile in previous studies by the group. Derivatives of the three original molecules were proposed. Overall the second modification (5-[2-(methoxycarbonyl)anilino]pentanoic acid, 5-[2-(propoxycarbonyl)anilino]pentanoic acid and 5-(2-{[(propan-2-yl)oxy]carbonyl}anilino)pentanoic acid) of all three original molecules was the one that achieved highest score in molecular docking and a better combination of the other parameters. Further research as in the obtaining of such derivatives via synthesis and their in vivo testing to confirm their higher pharmacological potential is currently on the way.