Rutamarin: Efficient Liquid–Liquid Chromatographic Isolation from Ruta graveolens L. and Evaluation of Its In Vitro and In Silico MAO-B Inhibitory Activity

Abstract

Naturally occurring coumarins are a group of compounds with many documented central nervous system (CNS) activities. However, dihydrofuranocoumarins have been infrequently investigated for their bioactivities at CNS level. Within the frame of this study, an efficient liquid–liquid chromatography method was developed to rapidly isolate rutamarin from Ruta graveolens L. (Rutaceae) dichloromethane extract (DCM). The crude DCM (9.78 mg/mL) and rutamarin (6.17 M) were found to be effective inhibitors of human monoamine oxidase B (hMAO-B) with inhibition percentages of 89.98% and 95.26%, respectively. The inhibitory activity against human monoamine oxidase A (hMAO-A) for the DCM extract was almost the same (88.22%). However, for rutamarin, it significantly dropped to 25.15%. To examine the molecular interaction of rutamarin with hMAO- B, an in silico evaluation was implemented. A docking study was performed for the two enantiomers (R)-rutamarin and (S)-rutamarin. The (S)-rutamarin was found to bind stronger to the hMAO-B binging cavity.

Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

“…Interestingly, the compounds with a higher in vitro inhibitory activity, 12 and 13 (Figure 15) were also the molecules with the highest affinity towards the catalytic site of MAO-B, interacting with the main amino acids of the active site (Tyr60, Leu171, Ile198, Tyr 398, and Tyr435) [110]. Similar strategies were carried out by other researchers to study the drug potential of garcinol (PDB#3PO7) [111], tricyclic molecules with xanthine scaffolds (PDB#2V5Z) [112], benzothiazoles and benzoxazoles (PDB#2V5Z) [113], rutamarin (PDB#2V60) [114], isoxazole carbohydrazides (PDB#2V60) [115], eugenol derivatives [116], and 4-(3-nitrophenyl)thiazol-2-yl hydrazone derivatives (PDB#6FW0) [117] in PD, as summarized in Figure 15. Moreover, the Chaurasiya research team also studied the affinity of several acacetin derivatives (Figure 16) by molecular docking and combined this analysis with molecular dynamics simulations to evaluate the compounds' binding modes and selectivity towards both MAO-A (PDB ID: 2Z5X) and MAO-B (PDB#4A79) isoforms [118].…”

Coumarins from Seseli devenyense Simonk.: Isolation by Liquid–Liquid Chromatography and Potential Anxiolytic Activity Using an In Vivo Zebrafish Larvae Model

“…The preliminary HPLC-DAD analysis of the SDMFE revealed the presence of several interesting coumarin compounds. The multi-solvent system HEMWat was previously shown to be efficient in separating compounds from other coumarin-rich sources [ 29 , 30 , 31 , 32 ]. Therefore, various HEMWat mixtures were tested in this work and, from these, HEMWat 2/5/2/5 ( v / v / v / v ) was selected for the separation of devenyol ( 1 ) and cis-khellactone ( 2 ), HEMWat 6/5/6/5 ( v / v / v / v ) for the separation of d-laserpitin ( 3 ) and isolaserpitin ( 4 ) and HEMWat 5/2/5/2 ( v / v / v / v ) for the separation of octanoyllomatin ( 5 ).…”

“…The partition coefficient (Pi), defined as the ratio of the concentration of a solute in the stationary phase to its concentration in the mobile phase, was used as the screening parameter. The experimental protocol was previously descried by Widelski et al (2018) [30]. Briefly, 1 mg of crude extract was dissolved in 4 mL of biphasic solvent systems obtained by mixing various volumes of hexane, ethyl acetate, methanol and water (HEMWat).…”

Ruta angustifolia Pers. (Narrow-Leaved Fringed Rue): Pharmacological Properties and Phytochemical Profile

“…Rutamarin is an anticancer furocoumarin derivative isolated from R. angustifolia Pers. [ 72 ] and other Ruta species [ 73 ]. The compound is moderately cytotoxic to colorectal adenocarcinoma HT29 cells (IC 50 = 5.6 μM), and induces cell cycle perturbations and caspase-dependent apoptosis [ 73 ].…”