Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret

Abstract

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2’-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC50 of 55 μg/mL (against AChE) and 60 μg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2, 2-diphenyl-1-picrylhydrazyl) and ABTS (2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50 values of 60 and 62 μg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC50 values for inhibition of the two enzymes were recorded as 90 and 92 μg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer’s disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.

Non-Alkaloid Cholinesterase Inhibitory Compounds from Natural Sources

“…Several terpenoids from natural sources have been reported as cholinesterase inhibi-tors [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. The compounds 1 – 11 , as shown in Supplementary Material ( Table S1 ), are of the Abietane-type diterpene skeletons isolated from Salvia austriaca , Salvia glutinosa , Caryopteris mongolica, and Perovskia atriplicifolia [ 14 , 15 , 16 ].…”

The Chemical Composition and Health-Promoting Effects of the Grewia Species—A Systematic Review and Meta-Analysis

“…As shown in Table 1, a wide variety of extracts/solvents and techniques were reported in the literature. In detail, 25.2% of the compounds were extracted with methanol in six studies [14,[21][22][23][24][25], 47.8% with acidified methanol in two studies [13,26], 11.7% with water in two studies [2,27], 5.04% with 50% methanol in one study [24], 4.20% with petroleum ether in one study [28], 3.36% with chloroform in two studies [15,29], 2.52% with ethyl acetate in one study [2], 1.68% with aqueous acetone in one study [30], and 1.68% with 80% methanol in one study [8]. Mass spectrometry was the most commonly employed technique for the identification of bioactive compounds (81.5%) wherein one study used ESI-MS/MS, one used LC-QToF-MS, one used GC-MS, and two used NMR spectroscopy.…”

“…Regarding the plant parts analyzed in each study, the fruits of G. asiatica were the most explored, with five articles studying fruits alone [2,13,21,24,26,30]. Two articles focused on G. asiatica leaves [8,41], two explored G. asiatica flowers [29,42], one studied Grewia optiva leaves [27], one studied G. asiatica stems [28] and each studied G. microcos [37] and G. lasiocarpa stems [15], G. tiliaefolia bark [22], G. hirsute leaves [23], and G. optiva roots [14] and stems [25] to identify the phytochemical constituents.…”

“…Eight categories of secondary metabolites were studied in fruits, four in stem bark, three in flowers, three were reported in leaves, and one in pomace. Out of 19 stud-ies, only 3 performed the quantitative analysis [8,13,26] whereas 16 articles without quantitative information of bioactive metabolites were reported [2,14,15,[21][22][23][24][25][27][28][29][30]37,[40][41][42].…”

Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment

“…Many active compounds have been isolated from some Grewia spp . In 2020 Bari et al were able to isolate and investigate antidiabetic, antioxidant, and anticholinesterase activity of four new compounds [ 153 ]. The best results were obtained for 2,2′-(1,4-phenylene) bis (3-methylbutanoic acid), which was labelled XII in that experiment.…”