ABSTRACT
From the aerial parts of Buxus hyrcana, three triterpenoidal alkaloids, 17-oxo-3-benzoylbuxadine (1), buxhyrcamine (2), and 31-demethylcyclobuxoviridine (3), along with 16 known compounds, cyclobuxoviridine (4), N(b)-dimethylcyclobuxoviricine (5), E-buxenone (6), Z-buxenone (7), moenjodaramine (8), homomoenjodarmine (9), buxamine A (10), buxamine B (11), 31-hydroxybuxamine B (12), N(20)-formylbuxaminol E (13), papillozine C (14), buxmicrophylline F (15), buxrugulosamine (16), cyclobuxophylline O (17), spirofornabuxine (18) and arbora-1,9(11)-dien-3-one (19) were isolated. Their structures were elucidated by using NMR spectroscopic methods. All of the compounds exhibited moderate to weak acetylcholinesterase, butyrylcholinesterase and glutathione S-transferase inhibitory activities. Compounds 1-19 also exhibited modest anti-fungal activities against Candidaalbicans. Compounds 1, 2, 8, 9 and 18 also exhibited weak anti-leishmanial activity.
Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Antiprotozoal Agents/isolation & purification , Antiprotozoal Agents/pharmacology , Buxus/chemistry , Cholinesterase Inhibitors/isolation & purification , Cholinesterase Inhibitors/pharmacology , Enzyme Inhibitors/isolation & purification , Enzyme Inhibitors/pharmacology , Leishmania/drug effects , Triterpenes/isolation & purification , Triterpenes/pharmacology , Acetylcholinesterase/drug effects , Alkaloids/chemistry , Antiprotozoal Agents/chemistry , Butyrylcholinesterase/drug effects , Candida albicans/drug effects , Cholinesterase Inhibitors/chemistry , Enzyme Inhibitors/chemistry , Glutathione Transferase , Nuclear Magnetic Resonance, Biomolecular , Triterpenes/chemistryABSTRACT
7alpha-Hydroxyfrullanolide (1), a known sesquiterpenoid, was isolated from Sphaeranthus indicus using an antibacterial-activity-directed fractionation method. This compound had exhibited a significant antibacterial activity against Gram-positive bacteria. Chemical and microbial reactions were performed to prepare eight different analogues of compound 1 in order to evaluate these newly synthesized compounds for antibacterial activity. These compounds were 1beta,7alpha-dihydroxyfrullanolide (2), 7alpha-hydroxy-1-oxofrullanolide (3), 4,5-dihydro-7alpha-hydroxyfrullanolide (4), 11,13-dihydro-7alpha-hydroxyfrullanolide (5), 13-acetyl-7alpha-hydroxyfrullanolide (6), 2alpha,7alpha-dihydroxysphaerantholide (7), 4alpha,5alpha-epoxy-7alpha-hydroxyfrullanolide (8), and 4beta,5beta-epoxy-7alpha-hydroxyfrullanolide (9). Microbial reactions on 1 using whole-cell cultures of Cunninghamella echinulata and Curvularia lunata yielded compounds 2-4. Incubation of compound 1 with the liquid cultures of Apsergillus niger and Rhizopus circinans yielded metabolites 5-7, while 8 and 9 were prepared by carrying out an epoxidation reaction on 1 using meta-chloroperbenzoic acid (mCPBA). Structures of compounds 2-9 were elucidated with the aid of extensive NMR spectral studies. Compounds 2-4 were found to be new metabolites. Compounds 1-9 were evaluated for antibacterial activity and found to exhibit a wide range of bioactivities. Antibacterial-activity data of 1-9 suggested that the bioactivity of 1 is largely due to the presence of C4=C5, C11=C13, and a gamma-lactone moiety.
Subject(s)
Anti-Bacterial Agents/chemistry , Sesquiterpenes/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Aspergillus niger/metabolism , Asteraceae/chemistry , Biotransformation , Cunninghamella/metabolism , Gram-Positive Bacteria/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Molecular Conformation , Rhizopus/metabolism , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacologyABSTRACT
Fungal catalysis of sclareolide (1) using Mucor plumbeus (ATCC 4740), Cunninghamella blakesleeana (ATCC 9245), Cunninghamella echinulata (ATCC 9244), Curvularia lunata (ATCC 12017) and Aspergillus niger (ATCC 1004), was performed. Cunninghamella blakesleeana (ATCC 9245) metabolized compound 1 to afford O(6)-sclareolide (2), 3beta,6alpha-dihydroxysclareolide (3), 9-hydroxysclareolide (4), along with three known metabolites, 1beta,3beta-dihydroxysclareolide (5), 3-oxosclareolide (6) and 3beta-hydroxysclareolide (7). Biotransformation experiments of compound 1 with Cunninghamella echinulata (ATCC 9244) also yielded two new compounds, 5-hydroxysclareolide (8), and 7beta-hydroxysclareolide (9) along with two known compounds 5 and 7. Spectroscopic methods were used to establish the structures of compounds 2-9. Compounds 2-9 exhibited modest acetylcholinesterase inhibitory activity.