Benzeneboronate of catecholic carboxyl methyl esters, N-acetyldopamine, coumarin and catechol estrogens were prepared as crystalline derivatives in high yield. Related catechol compounds with extra polar functional group(s) (OH, NH2) do not form or only partially form unstable cyclic boronate derivatives.
Crude glycoside extracts from the plant, Sarcolobus globosus, were tested on the rat phrenic nerve-diaphragm, chick biventer cervicis and frog rectus abdominis preparations. Nerve-stimulated twitches were inhibited by the extract. The muscle paralysis was not similar to that by curare-like blockers as it was not reversed by neostigmine or by a tetanus. Although contractures to acetylcholine or carbachol were not affected by 0.6 mg/ml of the extract, higher concentration of the extracts (3 mg/ml) depressed the log dose-response curve of acetylcholine and carbachol. The results suggest that the neuromuscular blocking effect of the extracts is either dose-dependent or due to a mixture of toxins with presynaptic or postsynaptic actions.
A new dienamide, (2E,4E)-7-(3',4'-dimethoxyphenyl)-N-ethyl-6-(R)-hydroxyhepta- 2,4-dienamide, named (-)-kunstleramide (1), were isolated from the bark of Beilschmiedia kunstleri Gamble together with one neolignan: (+)-kunstlerone (2) and seven known alkaloids: (+)-nornuciferine (3), (-)-isocaryachine (4), (+)-cassythicine (5), (+)-laurotetanine (6), (+)-boldine (7), noratherosperminine (8), (+)-N-demethylphyllocaryptine (9). Their structures were established from spectroscopic techniques, most notably 1D- and 2D-NMR, UV, IR, OR, circular dichroism (CD) spectra and LCMS-IT-TOF. (-)-Kunstleramide (1) exhibited very poor dose-dependent inhibition of DPPH activity, with an IC₅₀ value of 179.5 ± 4.4 μg/mL, but showed a moderate cytotoxic effect on MTT assays of A375, A549, HT-29, PC-3 and WRL-68 with EC₅₀ values of 64.65, 44.74, 55.94, 73.87 and 70.95 µg/mL, respectively.
Plants of the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders. Rauvolfia reflexa, a member of the family, has been used as an antidote for poisons and to treat malaria. The dichloromethane, ethanol and methanol extracts from the leaves of Rauvolfia reflexa showed potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, with IC50 values in the 8.49 to 52.23 g/mL range. Further cholinesterase inhibitory-guided isolation of these extracts afforded four bioactive compounds, namely: (E)-3-(3,4,5-trimethoxyphenyl)acrylic acid (1), (E)-methyl 3-(4-hydroxy-3,5-dimethoxyphenyl) acrylate (2), 17-methoxycarbonyl-14-heptadecaenyl-4-hydroxy-3-methoxycinnamate (3) and 1,2,3,4-tetrahydro-1-oxo-β-carboline (4). The isolated compounds showed moderate cholinesterase inhibitory activity compared to the reference standard, physostigmine. Compounds 1 and 2 showed the highest inhibitory activity against AChE (IC50 = 60.17 µM) and BChE (IC50 = 61.72 µM), respectively. Despite having similar molecular weight, compounds 1 and 2 were structurally different according to their chemical substitution patterns, leading to their different enzyme inhibition selectivity. Compound 2 was more selective against BChE, whereas compound 1 was a selective inhibitor of AChE. Molecular docking revealed that both compounds 1 and 2 were inserted, but not deeply into the active site of the cholinesterase enzymes.
Three independent mol-ecules of the title estrone derivative and a mol-ecule of methanol comprise the asymmetric unit of the title compound [systematic name: 13-methyl-6,7,8,9,11,12,13,14,15,16-deca-hydro-cyclo-penta-[a]phenanthren-3-ol-meth-an-ol (3/1)], 3C(18)H(24)O·CH(3)OH. Two of the estrone mol-ecules exhibit 50:50 disorder (one displays whole-mol-ecule disorder and the other partial disorder in the fused five- and six-membered rings) so that five (partial) mol-ecular conformations are discernable. The conformation of the six-membered ring abutting the aromatic ring is close to a half-chair in all five components. The conformation of the six-membered ring fused to the five-membered ring is based on a chair with varying degrees of distortion ranging from minor to significant. Two distinct conformations are found for the five-membered ring: in four mol-ecules, the five-membered ring is twisted about the bond linking it to the six-membered ring, and in the other, the five-membered ring is an envelope with the quaternary C atom being the flap atom. The crystal packing features O-H⋯O hydrogen bonding whereby the four mol-ecules comprising the asymmetric unit are linked into a supra-molecular chain along the b axis.
Two independent mol-ecules comprise the asymmetric unit of the title cholestane derivative, C(29)H(49)NO(3) {systematic name: (3S,8S,9S,10R,13R,14S,17R)-17-[(1R)-1,5-dimethyl-hex-yl]-6-hy-droxy-imino-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra-deca-hydro-1H-cyclo-penta-[a]phenanthren-3-yl ace-tate}. The major differences between the mol-ecules relate to the relative orientations of the terminal acetyl [C-C-O-C torsion angles = -158.8 (3) and -81.7 (3)°] and alkyl groups [C-C-C-C = 168.9 (3) and 65.8 (4)°]. In the crystal, the independent mol-ecules associate via pairs of O-H⋯N hydrogen bonds, forming dimeric aggregates. Supra-molecular layers in the ab plane are mediated by C-H⋯O inter-actions.
In the title cholestane derivative, C(28)H(48) [systematic name: (1S,2S,7R,10R,11R,14R,15R)-2,5,10,15-tetra-methyl-14-[(2R)-6-methyl-heptan-2-yl]tetra-cyclo-[8.7.0.0(2,7).0(11,15)]hepta-dec-4-ene], the cyclo-hexene ring adopts a half-chair conformation. The parent 5α-cholest-2-ene and the equivalent fragment of the title compound are almost superimposable (r.m.s. deviation = 0.033 Å).
The asymmetric unit of the title compound {systematic name: (3S,8S,9S,10R,13R,14S,17R)-17-[(E,2R,5S)-5-ethyl-6-methyl-hept-3-en-2-yl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodeca-hydro-1H-cyclo-penta-[a]phenanthren-3-yl p-toluene-sulfonate}, C(36)H(54)O(3)S, comprises two independent mol-ecules that differ significantly in terms of the relative orientations of the peripheral groups; the conformation about the C=C bond of the side chain is E. In the crystal, mol-ecules associate into linear supra-molecular chains aligned along the a axis via C-H⋯O inter-actions.
In the title anhydro-scymnol tetra-acetate, C(35)H(54)O(9), the fused chair conformation of the cyclo-hexane A/B ring junction is cis with a 5β-H configuration. The compound has a trimethyl-ene oxide ring at position 24,26 and four acetate groups at the 3α,7α,12α,27 positions.
In the title steroid derivative, C(23)H(37)IO, the fused cyclo-propane unit that comprises part of the A ring has a β-configuration, and the associated cyclo-pentane ring has an envelope conformation.
In the title compound (5S,8R,9R,10R,13S,14S,17R,20R)-24-bromo-5β-cholane, C(24)H(41)Br, the fused-chair conformation of the cyclo-hexane A/B ring junction is cis with a 5β-H configuration.
In the title steroid derivative, C(25)H(40)O(3), the fused cyclo-propane unit that corresponds to a part of the A ring has a β-configuration and the associated cyclo-pentane ring an envelope-shaped conformation.
In the crystal structure of 2-bromo-beclometasone dipropionate [systematic name: (8S,9R,10S,11S,13S,14S,16S,17R)-2-bromo-9α-chloro-11-hydr-oxy-10,13,16-trimethyl-3-oxo-17-[2-(propion-yloxy)acet-yl]-6,7,8,9,10,11,12,13,14,15,16,17-dodeca-hydro-3H-cyclo-penta-[a]phenanthren-17-yl propionate], C(28)H(36)BrClO(7), the six-membered ring with the 1,4-diene-3-one composition is planar (r.m.s. deviations = 0.03 and 0.04 Å for the two independent mol-ecules), whereas the remaining six-membered rings have chair conformations. Each of the independent mol-ecules self-associates via O-H⋯O(propionate) hydrogen bonding, generating a supra-molecular chain running along the b axis. The crystal is twinned, with the monoclinic unit cell emulating an orthorhomic crystal system; the major twin component constitutes approximately 60%.
In the crystal structure of (8S,9R,10S,11S,13S,14S,16S,17R)-9α-bromo-11-hydr-oxy-10,13,16-trimethyl-3-oxo-17-[2-(propion-yloxy)acet-yl]-6,7,8,9,10,11,12,13,14,15,16,17-dodeca-hydro-3H-cyclo-penta-[a]phenanthren-17-yl propionate monohydrate, C(28)H(37)BrO(7)·H(2)O, which has a 9α-Br atom in place of the 9α-Cl atom of monohydrated beclometasone dipropionate, one six-membered ring is planar (r.m.s. deviation = 0.02 Å) owing to its 1,4-diene-3-one composition, whereas the two other six-membered rings each have a chair conformation. The organic mol-ecule and water mol-ecules engage in hydrogen-bonding inter-actions, generating a helical chain running along the c axis of the ortho-rhom-bic unit cell.
The title compound, C(28)H(34)Cl(2)O(7), is a derivative of the glucocorticoid steroid beclomethasone dipropionate. It features an expoxide linkage [angle at oxygen = 96.6 (2)°]. The dichlorocyclohexenone ring adopts an envelope conformation, with the C atom bearing the two Cl substituents representing the flap. The dichloro-methyl C atom deviates by 0.471 (4) Å from the plane defined by the other five atoms, whose maximum r.m.s. deviation is 0.04 Å.
In the title compound, C(18)H(21)IO, the cyclo-hexane ring adopts a chair conformation, whereas the cyclo-pentane ring and the ten-membered tetra-line portions each adopt an envelope conformation. For the five-membered ring, the methine C atom deviates by 0.638 (4) Å (r.m.s. of the four other atoms is 0.005 Å) and for the ten-membered ring, the methine C atom constituting the flap deviates by 0.671 (3) Å (r.m.s. of the other nine atoms is 0.066 Å).
The title compound, C(30)H(34)O(5), crystallizes with two symmetry-independent mol-ecules in the asymmetric unit. In the crystal structure, the two independent mol-ecules are disposed about a pseudo-center of inversion. An intra-molecular O-H⋯O hydrogen bond is observed in each independent mol-ecule. The crystal structure is stabilized by C-H⋯O hydrogen bonds.
Five morphinoid alkaloids have been isolated from Dehaasia longipedicellata, namely (-) pallidine, a new alkaloid (+) pallidinine (1), (+)-milonine, (-) 8,14-dehydrosalutaridine and (-) sinoacutine.
Bioassay-guided fractionation of an ethyl acetate extract of Fissistigma lanuginosum led to the isolation of the known chalcone pedicin [1], which inhibited tubulin assembly into microtubules (IC50 value of 300 microM). From the same EtOAc fraction, two new condensed chalcones, fissistin [2] and isofissistin [3], which showed cytotoxicity against KB cells, were also obtained, together with the inactive dihydropedicin [4] and 6,7-dimethoxy-5,8-dihydroxyflavone [5]. In addition, the aminoquinones 6, 8, and 9 were isolated from the alkaloid extract. These compounds were artifacts, prepared by treatment of 1, 4, and 2, respectively, with NH4OH. The structures of the new compounds were elucidated by spectral methods, especially 2D nmr.
Interleukin-6 is one of the factors affecting sensitivity to cytotoxic agents. Therefore, the current study was designed to investigate the role of IL-6 and IL6 receptors in the cytotoxic effects of zerumbone in ovarian and cervical cancer cell lines (Caov-3 and HeLa, respectively). Exposure of both cancer cells to zerumbone or cisplatin demonstrated growth inhibition at a dose-dependent manner as determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,Sdiphenyltetrazolium bromide) reduction assay. Both laser scanning confocal microscopy and TUNEL assay showed typical apoptotic features in treated cells. The studies conducted seems to suggest that zerumbone induces cell death by stimulating apoptosis better than cisplatin, based on the significantly higher percentage of apoptotic cells in zerumbone's treated cancer cells as compared to cisplatin. In addition, zerumbone and cisplatin arrest cancer cells at G2/M phase as analyzed by flow cytometry. Our results indicated that zerumbone significantly decreased the levels of IL-6 secreted by both cancer cells. In contrast, HeLa and Caov-3 cells were still sensitive to cisplatin and zerumbone, even in the presence of exogenous IL-6. However, membrane-bound IL-6 receptor is still intact after zerumbone treatment as demonstrated using an immune-fluorescence technique. This study concludes that the compound, zerumbone inhibits both cancer cell growth through the induction of apoptosis, arrests cell cycle at G2/M phase and inhibits the secretion levels of IL-6 in both cancer cells. Therefore, zerumbone is a potential candidate as a useful chemotherapeutic agent in treating both cervical and ovarian cancers in future.