Aggregation Behavior of 6-Isocassine and N-Methyl-6-Isocassine: Insights into the Biological Mode of Action of Lipid Alkaloids

Abstract

The aggregation behavior of 6-isocassine and N-methyl-6-isocassine, two piperidin-3-ol alkaloids isolated respectively from the barks of Prosopis nigra and P. affinis, was investigated using a combination of NOE experiments and diffusion measurements in solvents of varying polarity and hydrogen bonding capacity. While the NOE enhancements for N-methyl-6-isocassine are positive, regardless of the solvent, those for 6-isocassine shift from negative to positive when going from chloroform-d to methanol-d 4 solution. In addition, despite the self-diffusion coefficients of both compounds being virtually identical in methanol-d 4 , N-methyl-6-isocassine diffuses nearly twice as fast as the non-methylated alkaloid in chloroform-d. The changes in rotational and translational dynamics observed between solvents for 6-isocassine suggest that the molecule forms dimeric head-to-head aggregates in non-polar aprotic environments, a behavior that could help explain the biological mode of action that has been proposed for this type of alkaloids.

Antimicrobial activity of the methanolic leaf extract of Prosopis laevigata

“…The contents of phenolic compounds and flavonoids were, in general, less than those reported by previous studies on the phytochemical composition of the leaves and flowers from the pods obtained from several Prosopis species 8 – 10 ; however, and even though the compounds detected through GC–MS and HPLC–MS had no matches with the available libraries, the partial results obtained by HPLC–DAD in the present study confirm the widespread presence of some simple phenols and catechol, a compound common in various plant species 14 – 16 . In the case of the alkaloids, these were in the range previously reported for various species of Prosopis 15 – 20 . Alkaloids, together with flavonoids, have been reported to be mainly responsible for the antimicrobial activity in this genus 8 – 10 , 17 , 19 .…”

“…The antioxidant activity of Prosopis spp. has been studied for several species and attributed to alkaloids and phenolic compounds present in the aerial parts of P. juliflora and P. laevigata 20 – 22 . However, in the present study, the obtained value (AC 50 = 334.78 ppm) is higher than that found in other studies 18 – 21 and could be related to the composition of the methanolic extract, probably due to the low concentration of phenolic compounds in comparison with previous studies 13 , 14 , 21 , 22 .…”

“…On the other hand, the studies by Salinas et al 24 , Khan et al 25 , and Valli et al 19 presented inhibitory concentrations of different solvent extracts from others Prosopis species that were less than 100 µg/mL. These activities could be related with the alkaloid fraction in the extracts, as several studies reported that characteristic alkaloids from this genus (like prosopine, cassine, prosoflorine and juliprosopine) had shown alterations to the plasma membrane permeability either by intercalating between the phospholipids that make it up or affecting the functions of some ion channels, thus provoking cell lysis 17 – 20 . In our study, the methanolic leaf extract showed important antibacterial activity, although it was less effective than the studies mentioned above.…”