ABSTRACT
A chemical investigation of the chloroform extract of the roots of Uvaria ludida Benth. (Annonaceae), an important African traditional medicine, led to the isolation of six new compounds; three pyrenes, 2-hydroxy-1,8-dimethoxypyrene (1), 8-methoxy-1,2-methylenedioxypyrene (2), and 7-hydroxy-8-methoxy-1,2-methylenedioxypyrene (3), two pyrenediones, 2-hydroxy-1,8-pyrenedione (4) and 2-methoxy-1,8-pyrenedione (5), and a sesquiterpene, (-)-10-oxo-isodauc-3-en-15-oic acid (6), together with eight known compounds (7-14). The structural elucidation by spectroscopic studies of the compounds isolated is described. While pyrenes did not exhibit strong cytotoxicity against human promyelocytic leukemia HL-60 cells, pyrenediones showed strong cytotoxicity. The IC(50) of 4 was 70 ng mL(-1), which was close to that of etoposide (IC(50) = 60 ng mL(-1)).
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Pyrenes/chemistry , Pyrenes/pharmacology , Uvaria/chemistry , Apoptosis/drug effects , HL-60 Cells , Humans , Molecular StructureABSTRACT
A chemical investigation of the chloroform extract of the roots of Uvaria welwitschii (Annonaceae), an African traditional medicine taken for stomach ache, led to the isolation of eight new compounds, named welwitschins A-H (1-8), together with five known compounds (9-13). The structural elucidation by spectroscopic studies of the compounds isolated is described. All new compounds were flavonoids having a 2-hydroxy-3,4,6-trimethoxyphenyl moiety in the A-ring, and unsubstituted phenyl in the B-ring. Four of them (1-4) were monomeric flavonoids while the others (5-8) were dimeric flavonoids. The cytotoxicity of the isolated compounds against human promyelocytic leukemia HL-60 cells was investigated.
Subject(s)
Annonaceae/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Plant Roots/chemistry , Cell Survival/drug effects , Chromatography, High Pressure Liquid , HL-60 Cells , Humans , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
In the present study, we attempted to elucidate the antinociceptive activity of Xylopia parviflora bark using the acetic acid-induced writhing test, hot plate test, and formalin test in mice. The MeOH extract (100 and 200 mg/kg, administered intraperitoneally (i.p.)) had an antinociceptive effect demonstrated by its inhibitory effects on writhing number induced by acetic acid. Three alkaloidal fractions exhibited significant antinociceptive effects in three animal models; the chloroform-soluble fraction, including secondary and tertiary alkaloids, exhibited the strongest effect. This result supported its use in folk medicine as an analgesic agent. We tested the main alkaloids of these fractions for their antinociceptive effects to clarify the active components. (+)-Corytuberine (6.3 and 12.5 mg/kg, i.p.) showed very strong activity, had a significant antinociceptive effect in the acetic acid-induced writhing test (with 49.4 and 98.9% reduction of writhes), in the hot plate test, and in the formalin test (with 55.4 and 90.6% inhibition during the first phase, and 73.9 and 99.9% during the second phase, respectively). (+)-Glaucine (12.5 and 25 mg/kg, i.p.) showed strong activity in three animal models, too. The activity of these compounds was also observed following oral administration in the acetic acid-induced writhing test.
Subject(s)
Alkaloids/pharmacology , Analgesics/pharmacology , Plant Extracts/pharmacology , Xylopia/chemistry , Alkaloids/administration & dosage , Alkaloids/isolation & purification , Analgesics/administration & dosage , Analgesics/isolation & purification , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Male , Medicine, African Traditional , Mice , Pain/drug therapy , Pain Measurement , Plant Bark , Plant Extracts/administration & dosageABSTRACT
A chemical investigation of the petroleum ether extract and chloroform extract of the root of Uvaria scheffleri Diels (Annonaceae) led to the isolation of two new compounds, named hydroxyespintanol (1) and schefflerichalcone (2), together with eight known compounds (3-10). The structural elucidation of compounds 1 and 2 by spectroscopic studies is described. The cytotoxicity of the isolated compounds against human promyelocytic leukemia HL-60 cells was studied. Among these, 2'-hydroxy-3',4',6'-trimethoxychalcone (5) exhibited cytotoxicity (IC(50) 12 microM), and espintanol (3), which was the main ingredient, also showed some cytotoxicity (IC(50) 44 microM).
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Leukemia, Promyelocytic, Acute/drug therapy , Plant Extracts/pharmacology , Uvaria/chemistry , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/isolation & purification , Chalcones/isolation & purification , Chalcones/pharmacology , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Inhibitory Concentration 50 , Phenylpropionates/isolation & purification , Phenylpropionates/pharmacology , Plant Extracts/administration & dosage , Plant Roots , Solvents/chemistry , Spectrum AnalysisABSTRACT
The antinociceptive effects of highly selective mu (DAMGO), delta (DPDPE) and kappa (U-50488 and U-69593) opioid agonists were evaluated following intraperitoneal (i.p.) administration in the naked mole-rat. A hot plate test set at 60 degrees C was used as a nociceptive test and the latency to the stamping of the right hind paw (response latency) was used as the end-point. DAMGO (5-10 mg/kg) and DPDPE (2.5-5 mg/kg) caused a naloxone-reversible significant decrease in the mean response latency. Subcutaneous injection of naloxonazine (20 mg/kg) 24h prior to the administration of DAMGO (5 mg/kg) also blocked the reduction in the response latency observed when DAMGO was injected alone. On the contrary, U-50488 (2.5-5 mg/kg) or U-69593 (0.08 or 0.1 mg/kg) caused a naloxone-reversible significant increase in the mean response latency. These results showed that activation of mu or delta receptors caused hyperalgesia, whereas activation of kappa receptors caused antinociception in the hot plate test in naked mole-rat. This suggests that mu and delta receptors modulate thermal pain in a different way than kappa receptors in the naked mole-rat. It is not possible at the moment to point out how they modulate thermal pain as little is known about the neuropharmacology of the naked mole-rat.
Subject(s)
Hyperalgesia/metabolism , Mole Rats/metabolism , Nerve Fibers, Unmyelinated/metabolism , Nociceptors/metabolism , Receptors, Opioid, delta/metabolism , Receptors, Opioid, mu/metabolism , Analgesics, Opioid/pharmacology , Animals , Disease Models, Animal , Female , Hot Temperature/adverse effects , Hyperalgesia/chemically induced , Hyperalgesia/physiopathology , Male , Narcotic Antagonists/pharmacology , Nerve Fibers, Unmyelinated/drug effects , Nociceptors/drug effects , Nociceptors/physiopathology , Pain Measurement/methods , Pain Threshold/drug effects , Pain Threshold/physiology , Reaction Time/drug effects , Reaction Time/physiology , Receptors, Opioid, delta/agonists , Receptors, Opioid, delta/antagonists & inhibitors , Receptors, Opioid, kappa/agonists , Receptors, Opioid, kappa/antagonists & inhibitors , Receptors, Opioid, kappa/metabolism , Receptors, Opioid, mu/agonists , Receptors, Opioid, mu/antagonists & inhibitors , Skin/innervation , Skin/physiopathology , Thermosensing/drug effects , Thermosensing/physiologyABSTRACT
From the secondary and tertiary alkaloidal fractions of the root and the bark of Xylopia parviflora (Annonaceae), the isoquinoline alkaloids, 10,11-dihydroxy-1,2-dimethoxynoraporphine and parvinine were isolated, along with 39 known alkaloids. Their structures were determined on the basis of analysis of spectroscopic data.
Subject(s)
Alkaloids/chemistry , Annonaceae/chemistry , Isoquinolines/chemistry , Alkaloids/isolation & purification , Isoquinolines/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plants, Medicinal/chemistryABSTRACT
From the quaternary alkaloidal fraction of the bark and the root of Xylopia parviflora (Annonaceae), four isoquinoline alkaloids, xylopinidine, dehydrocoreximine, N, N-dimethylanomurine and N-methylphoebine were isolated along with the known compounds, pycnarrhine, lotusine, 6,7-dimethoxy-2-methyl-isoquinolinium salt, 1,2-dehydroreticuline, (-)-phellodendrine, (+)-tembetarine, (-)-litcubine, (+)-magnoflorine, tetradehydroreticuline, (-)-oblongine, (+)-menisperine, (+)-N-methylcorydine, stepharanine, (+)-xanthoplanine, dehydrodiscretine, jatrorrhizine and palmatine. 3,4-Dihydro-6,7-dimethoxy-2-methyl-isoquinolinium and N-methylpurpuerine were isolated as natural products for the first time. Their structures were determined on the basis of spectroscopic evidence.
Subject(s)
Alkaloids/chemistry , Annonaceae/chemistry , Isoquinolines/chemistry , Alkaloids/isolation & purification , Isoquinolines/isolation & purification , Mass Spectrometry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Bark/chemistry , Plant Roots/chemistry , Spectrophotometry, UltravioletABSTRACT
Two new C-benzylated dihydrochalcones, isochamuvaritin (1) and acumitin (2), have been isolated from the African medicinal plant Uvaria acuminata, together with the previously reported benzylbenzoate (3), uvaretin (4), isouvaretin (5), diuvaretin (6), and uvangoletin (7). The structural elucidation of compounds 1 and 2 in spectroscopic studies is described. C-Benzylated dihydrochalcones, especially 1, 2, 4, and 6, showed considerable cytotoxicity toward human promyelocytic leukemia HL-60 cells.
