title: New ursane triterpenoids from Ficus pandurata and their binding affinity for human cannabinoid and opioid receptors.
abstract: Phytochemical investigation of Ficus pandurata Hance (Moraceae) fruits has led to the isolation of two new triterpenoids, ficupanduratin A [1β-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (11) and ficupanduratin B [21α-hydroxy-3β-acetoxy-11α-methoxy-urs-12-ene] (17), along with 20 known compounds: α-amyrin acetate (1), α-amyrin (2), 3β-acetoxy-20-taraxasten-22-one (3), 3β-acetoxy-11α-methoxy-olean-12-ene (4), 3β-acetoxy-11α-methoxy-12-ursene (5), 11-oxo-α-amyrin acetate (6), 11-oxo-β-amyrin acetate (7), palmitic acid (8), stigmast-4,22-diene-3,6-dione (9), stigmast-4-ene-3,6-dione (10), stigmasterol (12), β-sitosterol (13), stigmast-22-ene-3,6-dione (14), stigmastane-3,6-dione (15), 3β,21β-dihydroxy-11α-methoxy-olean-12-ene (16), 3β-hydroxy-11α-methoxyurs-12-ene (18), 6-hydroxystigmast-4,22-diene-3-one (19), 6-hydroxystigmast-4-ene-3-one (20), 11α,21α-dihydroxy-3β-acetoxy-urs-12-ene (21), and β-sitosterol-3-O-β-D-glucopyranoside (22). Compound 21 is reported for the first time from a natural source. The structures of the 20 compounds were elucidated on the basis of IR, 1D ((1)H and (13)C), 2D ((1)H-(1)H COSY, HSQC, HMBC and NOESY) NMR and MS spectroscopic data, in addition to comparison with literature data. The isolated compounds were evaluated for their anti-microbial, anti-malarial, anti-leishmanial, and cytotoxic activities. In addition, their radioligand displacement affinity on opioid and cannabinoid receptors was assessed. Compounds 4, 11, and 15 exhibited good affinity towards the CB2 receptor, with displacement values of 69.7, 62.5 and 86.5 %, respectively. Furthermore, the binding mode of the active compounds in the active site of the CB2 cannabinoid receptors was investigated through molecular modelling.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Port Said University, Port Said, 42526, Egypt.
authors.forename: Amgad I M
authors.initials: AI
authors.lastname: Khedr
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah Al Munawarah, 30078, Saudi Arabia. sabrinshaur@gmail.com.|Department of Pharmacognosy, Faculty of Pharmacy, Assuit University, Assuit, 71526, Egypt. sabrinshaur@gmail.com.
authors.forename: Sabrin R M
authors.initials: SR
authors.lastname: Ibrahim
authors.affiliation: Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.|Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assuit Branch, Assuit, 71524, Egypt.
authors.forename: Gamal A
authors.initials: GA
authors.lastname: Mohamed
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah Al Munawarah, 30078, Saudi Arabia.|Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Hany E A
authors.initials: HE
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Assuit University, Assuit, 71526, Egypt.
authors.forename: Amany S
authors.initials: AS
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Assuit University, Assuit, 71526, Egypt.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ramadan
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Port Said University, Port Said, 42526, Egypt.
authors.forename: Atef E Abd
authors.initials: AE
authors.lastname: El-Baky
authors.affiliation: Garden for Medicinal Plants, Graduate School of Biomedical Sciences, Nagasaki University, Bunkyo-machi 1-14, Nagasaki, 852-8521, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: National Center for Natural Products Research, and Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
authors.forename: Samir A
authors.initials: SA
authors.lastname: Ross
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D030681:Ficus; D005638:Fruit; D006801:Humans; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D043882:Receptors, Cannabinoid / Q000737:chemistry / Q000378:metabolism*; D011957:Receptors, Opioid / Q000737:chemistry / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D014709:Vero Cells; D053978:Pentacyclic Triterpenes
chemical_list: D010936:Plant Extracts; D043882:Receptors, Cannabinoid; D011957:Receptors, Opioid; D014315:Triterpenes; C000606873:ursane; D053978:Pentacyclic Triterpenes
keywords: Anti-leishmanial; Anti-malarial; Cannabinoid receptors; Ficus pandurata; Opioid receptors; Triterpenes