- Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis
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A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 μM and 16.40 μM, respectively. The intracellular amastigotes assays showed IC50 = 22.00 μM (22) and 17.00 μM (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase.
- De Melos, Jorge Luiz R.,Torres-Santos, Eduardo Caio,Fai?es, Viviane Dos S.,De Nigris Del Cistia, Catarina,Sant'Anna, Carlos Maurício R.,Rodrigues-Santos, Cláudio Eduardo,Echevarria, Aurea
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p. 409 - 417
(2015/09/28)
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- A facile two-step synthesis of 2-arylbenzofurans based on the selective cross McMurry couplings
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(Chemical Equation Presented) A novel two-step synthesis of 2-arylbenzofurans has been developed. It involves a selective cross McMurry coupling of a salicylaldehyde or substituted salicylaldehyde with an aromatic aldehyde and a sequential oxidative cyclization of the resulting ortho-vinylphenols. Utilizing this synthetic protocol, a variety of 2-arylbenzofurans including cicerfuran (5) have been efficiently synthesized.
- Duan, Xin-Fang,Zeng, Jing,Zhang, Zhan-Bin,Zi, Guo-Fu
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p. 10283 - 10286
(2008/04/05)
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- Synthesis of cicerfuran, an antifungal benzofuran, and some related analogues
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Routes were investigated for the synthesis of cicerfuran, a hydroxylated benzofuran from wild chickpea implicated in resistance to Fusarium wilt, and some of its analogues. A novel method is described for the synthesis of oxygenated benzofurans by epoxidation and cyclisation of 2′-hydroxystilbenes. The stilbene intermediates required could be synthesised by palladium-catalysed coupling of styrenes with mono-oxygenated aryl halides but not with di-oxygenated aryl halides. Stilbenes corresponding to the latter were synthesised by Wittig reactions.
- Aslam, Shazia N.,Stevenson, Philip C.,Phythian, Sara J.,Veitch, Nigel C.,Hall, David R.
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p. 4214 - 4226
(2007/10/03)
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- Endothelin receptor antagonists
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Novel N-phenyl imidazole derivatives, pharmaceutical compositions containing these compounds and their use as endothelin receptor antagonists are described.
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- Total Synthesis of Carpacin and Its Geometric Isomer as a Cancer Chemopreventer
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Carpacin (1a), an antidepressant in Asiatic folk medicine from the Carpano tree, is achieved in which the longest linear sequence is only four steps in over all yield 67 percent from commercially available Sesamol. The key transformations in the synthesis are the selective palladium-catalyzed coupling reactions of aryl bromide with Grignard reagents. The first preparation of its geometric isomer (1b) is described. Highlights of the synthesis include Pd-ctalyzed coupling, selective hydrogenation, and Wittig reactions. Carpacin was examined as a potential inhibitor of carcinogenesis.
- Tseng, Tsui-Hwa,Tsheng, Yen-Min,Lee, Yean-Jang,Hsu, Hsing-Ling
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p. 1165 - 1170
(2007/10/03)
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- ENDOTHELIN RECEPTOR ANTAGONISTS
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Novel pyridines, pyrimidines, pyrazines, pyridazines and triazines, pharmaceutical compositions containing these compounds and their use as endothelin receptor antagonists are described.
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- ENDOTHELIN RECEPTOR ANTAGONISTS
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Novel indane and indene derivatives are described which are endothelin receptor antagonists.
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- Synthesis of Alkoxy-Substituted Diaryl Compounds and Correlation of Ring Separation with Inhibition of Tubulin Polymerization: Differential Enhancement of Inhibitory Effects under Suboptimal Polymerization Reaction Conditions
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A number of cytostatic compounds (2-4, 7, and 8), which can be described as "diaryl", inhibit tubulin polymerization, cause cells to accumulate in mitotic arrest, and competitively inhibit the binding of colchicine to tubuline.They differ, however, in the separation of the two aryl moieties.To attempt to understand this variability we prepared a series of analogues modeled on 3 and 4 ("benzodioxole series") and on 7 and 8 ("combretastatin series") which differed only in the number of methylene units (ranging from none to four) separating the aryl moieties.These compounds were evaluated for their effects on tubulin polymerization, colchicine binding, and the growth of L1210 murine leukemia cells.In terms of inhibitory effects on tubulin polymerization, for the combretastatin series there was an optimal separation of the two phenyl rings by a two-carbon bridge (compound 24), with progressively decreasing inhibitory activity when the separation was by one carbon (20), three carbons (25), or four carbons (28) (the biphenyl analogue 16 was inactive).The benzodioxole series, however, did not permit us to generalize this finding, because the least active agents prepared (39 and 40) had a two-carbon bridge, while those with one- (5 and 6) and three-carbon (46 and 47) bridges were nearly equivalent in potency.Submicromolar (IC50 values for inhibition of L1210 cell growth were only obtained for compounds 20 (IC50 0.2 μM), 24 (0.07 μM), and 25 (0.4 μM).While evaluating the effects of these agents on tubulin polymerization, we noted with the combretastatin series and with several standard agents that apparent potency (in terms of IC50 values) was always lower if the reaction was performed at 30 deg C, with 0.25 mM MgCl2, than at 37 deg C, with 1.0 mM MgCl2.This enhancement of IC50 values in the former system as compared with the latter was particularly dramatic for the less active agents (e.g., 28) as compared with the more active (e.g., 24).
- Getahun, Zelleka,Jurd, Leonard,Chu, Ping S.,Lin, Chii M.,Hamel, Ernest
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p. 1058 - 1067
(2007/10/02)
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- Total Synthesis of Isoflavones: Jamaicin, Calopogonium Isoflavone-B, Pseudobaptigenin, and Maxima Substance-B. Friedel-Crafts Acylation Reactions with Acid-Sensitive Substrates
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The Friedel-Crafts acylation reaction was studied on several acid-sensitive substrates.Under the proper conditions of varying Lewis acids, solvents, and reaction temperatures, the acylation indeed took place, thus obviating the necessity for functional group protection-deprotection sequences.By use of these procedures, the naturally occuring isoflavones jamaicin (1), calopogonium isoflavone-B (2), maxima substance-B (30), and pseudobaptigenin (31) were synthesized and characterized.
- Schuda, Paul Francis,Price, William A.
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p. 1972 - 1979
(2007/10/02)
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- New Sesamol Ethers as Pyrethrum Synergists
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Several new methylenedioxyphenyl (MDP) ethers were synthesised from sesamol and methoxy substituted sesamols and screened as pyrethrum synergists.In general, the synergistic activity increased with the methoxyl substituents and decreased in the corresponding alkenyl analogs.The synergistic activity of alkyl ethers was found to vary with the alkyl chain, n-propyl ethers showing the maximum.In the case of alkenyl ethers, the activity followed the order γ,γ-dimethyl allyl > β-methallyl > allyl and showed no correlation between Rm and synergistic activity.
- Devakumar, C.,Saxena, V. S.,Mukerjee, S. K.
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p. 725 - 730
(2007/10/02)
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- REVISED STRUCTURE AND SYNTHESIS OF PIPEROLEIN ACIDS, GUINEENSINE AND WISANINE FROM PIPER GUINEENSE
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The structures of piperolein acids guineensine and wisanine have been confirmed by synthesis.UV irradiation of trans piperolein B acid ester gave the cis-isomer reported in the literature as the trans-isomer.The trans-2, trans-4 ethylenic bonds in guineensine and wisanine were introduced by reacting piperolein B aldehyde and 2-methoxy piperonal with the appropriate Wittig or Reformatsky reagent.
- Okwute, S. K.,Okogun, J. I.,Okorie, D. A.
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p. 2541 - 2546
(2007/10/02)
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- Studies on the chemical constituents of rutaceous plants. XLIX. Development of a versatile method for the synthesis of antitumor-active benzo[c]phenanthridine alkaloids. (1). Preparation of various 2,4-bisaryl-4-oxobutyronitriles and 2,4-bisaryl-4-oxobutyramides
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For the sake of establishment of a versatile synthetic method for benzo[c]phenanthridine alkaloids, improvement of the Robinson synthetic method was examined. Thirteen chalcones (7a-m) were prepared by condensation of two acetophenone derivatives (15 and 16) with eleven benzaldehyde derivatives (19a-k) as fundamental starting materials. Hydrocyanation of these chalcones (7a-1) except one (7m) gave the corresponding 2,4-bisaryl-4-oxobutyronitriles (8a-1). Eleven 2,4-bisaryl-4-oxobutyramides (9a-k) were also prepared.
- Ishii,Ishikawa,Deushi,et al.
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p. 3024 - 3038
(2007/10/02)
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