Hyaluronidase Inhibitory Activity of Pentacylic Triterpenoids from Prismatomeris tetrandra (Roxb.) K. Schum: Isolation, Synthesis and QSAR Study

Abstract

The mammalian hyaluronidase degrades hyaluronic acid by the cleavage of the β-1,4-glycosidic bond furnishing a tetrasaccharide molecule as the main product which is a highly angiogenic and potent inducer of inflammatory cytokines. Ursolic acid 1, isolated from Prismatomeris tetrandra, was identified as having the potential to develop inhibitors of hyaluronidase. A series of ursolic acid analogues were either synthesized via structure modification of ursolic acid 1 or commercially obtained. The evaluation of the inhibitory activity of these compounds on the hyaluronidase enzyme was conducted. Several structural, topological and quantum chemical descriptors for these compounds were calculated using semi empirical quantum chemical methods. A quantitative structure activity relationship study (QSAR) was performed to correlate these descriptors with the hyaluronidase inhibitory activity. The statistical characteristics provided by the best multi linear model (BML) (R2 = 0.9717, R2cv = 0.9506) indicated satisfactory stability and predictive ability of the developed model. The in silico molecular docking study which was used to determine the binding interactions revealed that the ursolic acid analog 22 had a strong affinity towards human hyaluronidase.

The Potential of Triterpenoids from Loquat Leaves (Eriobotrya japonica) for Prevention and Treatment of Skin Disorder

“…It seems that the stimulation of hyaluronic acid synthesis by triterpenoids could also account for the inhibitory effect on hyaluronidase, an enzyme that degrades hyaluronic acid by cleaving the N -acetylglucosamidic bonds of hyaluronic acid via a β-elimination process to produce hyaluronic acid oligosaccharides [35]. …”

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“…[14] Recently, Abdullah et al had further investigated this species and obtained three pentacylic triterpenoids; namely ursolic acid 48, 3β,19,23-trihydroxyurs-12-en-28-oic acid 67, and 3β-acetylolean-12-en-28-oic acid 43. [26] P. glabra (Korth.) Valeton P. glabra is a tropical plant, grows on hillsides and ridges of tropical forests at altitudes up to 700 m in Peninsular Malaysia, Sumatra, and Borneo.…”

Bioassay-Guided Isolation, Metabolic Profiling, and Docking Studies of Hyaluronidase Inhibitors from Ravenala madagascariensis

“…Thus, components that suppress the enzymes or play as antioxidants reduce wrinkle forming [4]. Hyaluronidase enzyme is a mucopolysaccharide-hydrolyzing enzyme that causes the degradation of hyaluronic acid (HA), an important small molecule, which fills the space between collagen and elastin fibers, and helps maintain skin moisture levels [5][6][7][8][9]. It serves as an integral part of the extracellular matrix and is responsible for improving hydration which improves the appearance of fine lines and wrinkles [6,[10][11][12].…”