ABSTRACT
The crystal structures of four thio-phene-carbohydrazide-pyridine derivatives, viz. N'-[(E)-pyridin-3-yl-methyl-idene]thio-phene-2-carbohydrazide, C11H9N3OS, (I), N'-[(E)-pyridin-2-yl-methyl-idene]thio-phene-2-carbohydrazide, C11H9N3OS, (II), N-methyl-N'-[(E)-pyridin-2-yl-methyl-idene]thio-phene-2-carbohydrazide, C12H11N3OS, (III) and N'-[(E)-pyridin-2-yl-methyl-idene]-2-(thio-phen-2-yl)ethano-hydrazide, C12H11N3OS, (IV) are described. The dihedral angles between the thio-phene ring and the pyridine ring are 21.4â (2), 15.42â (14), 4.97â (8) and 83.52â (13)° for (I)-(IV), respectively. The thio-phene ring in (IV) is disordered over two orientations in a 0.851â (2):0.149â (2) ratio. Key features of the packing include N-Hâ¯Np (p = pyridine) hydrogen bonds in (I), which generate C(7) chains propagating in the [001] direction; N-Hâ¯Np links also feature in (II), but in this case they lead to C(6) [001] chains; in (IV), classical amide (C4) N-Hâ¯O links result in [010] chains; in every case adjacent mol-ecules in the chains are related by 21 screw axes. There are no classical hydrogen bonds in the extended structure of (III). Various weak C-Hâ¯X (X = O, N, S) inter-actions occur in each structure, but no aromatic π-π stacking is evident. The Hirshfeld surfaces and fingerprint plots for (I)-(IV) are compared.
ABSTRACT
The syntheses and crystal structures of five 2-benzyl-idene-1-benzosuberone [1-benzosuberone is 6,7,8,9-tetra-hydro-5H-benzo[7]annulen-5-one] derivatives, viz. 2-(4-meth-oxy-benzyl-idene)-1-benzosuberone, C19H18O2, (I), 2-(4-eth-oxy-benzyl-idene)-1-benzosuberone, C20H20O2, (II), 2-(4-benzyl-benzyl-idene)-1-benzosuberone, C25H22O2, (III), 2-(4-chloro-benzyl-idene)-1-benzosuberone, C18H15ClO, (IV) and 2-(4-cyano-benzyl-idene)-1-benzosuberone, C19H15NO, (V), are described. The conformations of the benzosuberone fused six- plus seven-membered ring fragments are very similar in each case, but the dihedral angles between the fused benzene ring and the pendant benzene ring differ somewhat, with values of 23.79â (3) for (I), 24.60â (4) for (II), 33.72â (4) for (III), 29.93â (8) for (IV) and 21.81â (7)° for (V). Key features of the packing include pairwise C-Hâ¯O hydrogen bonds for (II) and (IV), and pairwise C-Hâ¯N hydrogen bonds for (V), which generate inversion dimers in each case. The packing for (I) and (III) feature C-Hâ¯O hydrogen bonds, which lead to [010] and [100] chains, respectively. Weak C-Hâ¯π inter-actions consolidate the structures and weak aromatic π-π stacking is seen in (II) [centroid-centroid separation = 3.8414â (7)â Å] and (III) [3.9475â (7)â Å]. A polymorph of (I) crystallized from a different solvent has been reported previously [Dimmock et al. (1999 â¸) J. Med. Chem. 42, 1358-1366] in the same space group but with a packing motif based on inversion dimers resembling that seen in (IV) in the present study. The Hirshfeld surfaces and fingerprint plots for (I) and its polymorph are com-pared and structural features of the 2-benzyl-idene-1-benzosuberone family of phases are surveyed.
ABSTRACT
A 1:1 epimeric mixture of 3-[(4-nitro-benzyl-idene)amino]-2(R,S)-(4-nitro-phen-yl)-5(S)-(propan-2-yl)imidazolidin-4-one, C19H19N5O5, was isolated from a reaction mixture of 2(S)-amino-3-methyl-1-oxo-butane-hydrazine and 4-nitro-benz-alde-hyde in ethanol. The product was derived from an initial reaction of 2(S)-amino-3-methyl-1-oxo-butane-hydrazine at its hydrazine group to provide a 4-nitro-benzyl-idene derivative, followed by a cyclization reaction with another mol-ecule of 4-nitro-benzaldehyde to form the chiral five-membered imidazolidin-4-one ring. The formation of the five-membered imidazolidin-4-one ring occurred with retention of the configuration at the 5-position, but with racemization at the 2-position. In the crystal, N-Hâ¯O(nitro) hydrogen bonds, weak C-Hâ¯O(carbon-yl) and C-Hâ¯O(nitro) hydrogen bonds, as well as C-Hâ¯π, N-Hâ¯π and π-π inter-actions, are present. These combine to generate a three-dimensional array. Hirshfeld surface analysis and PIXEL calculations are also reported.
ABSTRACT
The crystal structures of four (E)-meth-oxy-benzaldehyde oxime derivatives, namely (2-meth-oxy-benzaldehyde oxime, 1, 2,3-di-meth-oxy-benzaldehyde oxime, 2, 4-di-meth-oxy-benzaldehyde oxime, 3, and 2,5-di-meth-oxy-benzaldehyde oxime, 4, are discussed. The arrangements of the 2-meth-oxy group and the H atom of the oxime unit are s-cis in compounds 1-3, but in both independent mol-ecules of compound 4, the arrangements are s-trans. There is also a difference in the conformation of the two mol-ecules in 4, involving the orientations of the 2- and 5-meth-oxy groups. The primary inter-molecular O-H(oxime)â¯O(hy-droxy) hydrogen bonds generate C(3) chains in 1 and 2. In contrast, in compound 3, the O-H(oxime)â¯O(hy-droxy) hydrogen bonds generate symmetric R 2 2(6) dimers. A more complex dimer is generated in 4 from the O-H(oxime)â¯O(hy-droxy) and C-H(2-meth-oxy)â¯O(hy-droxy) hydrogen bonds. In all cases, further inter-actions, C-Hâ¯O and C-Hâ¯π or π-π, generate three-dimensional arrays. Hirshfeld surface and fingerprint analyses are discussed.
ABSTRACT
The crystal structures of three salicyaldoxime compounds, namely 2-hy-droxy-4-methyl-benzaldehyde oxime, C8H9NO2, 1, 2,4-di-hydroxy-benzaldehyde oxime, C7H7NO3, 2, and 2-hy-droxy-4-meth-oxy-benzaldehyde oxime, C8H9NO3, 3, are discussed. In each compound, the hydroxyl groups are essentially coplanar with their attached phenyl group. The inter-planar angles between the C=N-O moieties of the oxime unit and their attached phenyl rings are 0.08â (9), 1.08â (15) and 6.65â (15)° in 1, 2 and 3, respectively. In all three mol-ecules, the 2-hy-droxy group forms an intra-molecular O-Hâ¯N(oxime) hydrogen bond. In compound (1), inter-molecular O-H(oxime)â¯O(hydrox-yl) hydrogen bonds generate R 2 2(14) dimers, related by inversion centres. In compound 2, inter-molecular O-H(oxime)â¯O(4-hy-droxy) hydrogen bonds generate C9 chains along the b-axis direction, while O-H(4-hydrox-yl)â¯O(2-hydrox-yl) inter-actions form zigzag C6 spiral chains along the c-axis direction, generated by a screw axis at 1, y, 1/4: the combination of the two chains provides a bimolecular sheet running parallel to the b axis, which lies between 0-1/2 c and 1/2-1 c. In compound 3, similar C9 chains, along the b-axis direction are generated by O-H(oxime)â¯O(4-meth-oxy) hydrogen bonds. Further weaker, C-Hâ¯π (in 1), π-π (in 2) and both C-Hâ¯π and π-π inter-actions (in 3) further cement the three-dimensional structures. Hirshfeld surface and fingerprint analyses are discussed.
ABSTRACT
Mitoxantrone is an anthracene-based anticancer agent whose efficacy in treating autoimmune diseases is believed to be due to cytotoxicity and inhibition of proliferation of cells. Several novel anthraquinone derivatives, analogs of mitoxantrone, were designed and synthesized. Lipophilic and functionalized mitoxantrone analogs were prepared by a simple methodology and the cytotoxicity and the inhibitory effect on nitric oxide release of these compounds were demonstrated in vitro on J774A.1 macrophages. Interestingly compounds 3, 4, 5, 6, 7, and 8 exhibited reduction in NO release (62.4%, 92.6%, 73.4%, 58.4%, 57.8% and 53.4%, respectively) in comparison to NG-n-methyl-arginine treated control, without cytotoxicity. In conclusion, anthraquinone derivatives were prepared in a good yield and showed promissory antiinflammatory properties.
Subject(s)
Anthraquinones/toxicity , Macrophages/drug effects , Animals , Anthraquinones/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/toxicity , Cell Line , Cell Proliferation/drug effects , Humans , Molecular Structure , Nitric Oxide/biosynthesisABSTRACT
The present study investigated the effects of the anthraquinone derivative (O,O'-bis-(3'-iodopropyl)-1,4-dihidroxyanthraquinone - DIPDHAQ), mitoxantrone analog, in an experimental autoimmune encephalomyelitis (EAE) model. The results showed that DIPDHAQ treatment improved the clinical signs of the disease (n=10; vehicle: 3.8 ± 0.3; DIPDHAQ: 1.4 ± 0.9). The improvement was associated with a decrease of inflammatory cells, demyelination, IL-17, IFN-γ, IL-12p40, IL-6, TGF-ß, CCL5 and CCL20 levels in the spinal cord. DIPDHAQ presented a low cytotoxicity when in vitro assays were performed. Therefore, the findings suggest a major role for DIPDHAQ in multiple sclerosis, disease characterized as an autoimmune inflammatory disorder against myelin proteins of the brain and spinal cord. The attenuation of inflammation and consequently improvement of clinical signs, involving a decrease of pro-inflammatory cytokines and the low cytotoxicity of DIPDHAQ, suggest that this compound could be used as an alternative treatment for autoimmune diseases in the central nervous system.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Macrophages, Peritoneal/drug effects , Mitoxantrone/analogs & derivatives , Multiple Sclerosis/drug therapy , Spinal Cord/drug effects , Animals , Cell Line , Cell Movement/drug effects , Cell Survival/drug effects , Cytokines/metabolism , Encephalomyelitis, Autoimmune, Experimental/immunology , Female , Humans , Immunity/drug effects , Immunomodulation , Inflammation Mediators/metabolism , Macrophages, Peritoneal/pathology , Mice , Mice, Inbred C57BL , Mitoxantrone/therapeutic use , Multiple Sclerosis/immunology , Spinal Cord/metabolism , Spinal Cord/pathologyABSTRACT
In this work, 17 new N-acylhydrazone derivatives of amino acids have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. The compounds 8b, 8e, 8f, 9a-d, and 10c exhibited an important minimum inhibitory concentration activity between 12.5 and 50 µg/mL, which can be compared with that of the tuberculostatic drug d-cycloserine (20 µg/mL).
Subject(s)
Amino Acids/chemistry , Antitubercular Agents/chemical synthesis , Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Antitubercular Agents/chemistry , Cycloserine/pharmacology , Hydrazones/chemical synthesis , Hydrazones/chemistry , Hydrazones/pharmacology , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
In this work, a number of lipidic amino alcohols wereas synthesized and evaluated in vitro on cultures of Leishmania amazonensis and Leishmania chagasi. Nine amino alcohols showed inhibition of L. chagasi growth, and seven of them showed inhibition of L. amazonensis with IC(50) below 10 microm. Compound 11f was more active than the reference drug amphotericin B against L. chagasi promastigote forms.
Subject(s)
Amino Alcohols/chemical synthesis , Leishmania/drug effects , Trypanocidal Agents/chemical synthesis , Amino Alcohols/chemistry , Amino Alcohols/pharmacology , Amphotericin B/pharmacology , Humans , Leishmania/growth & development , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacologyABSTRACT
A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol were synthesized and tested for their antitubercular activity. Compounds 3, 8 and 9 were found to be the most active (MIC of 6.25 microg/mL). Nine other compounds displayed activity against Mycobacterium tuberculosis, with a MIC of 12.5 microg/mL.
Subject(s)
Amino Alcohols/pharmacology , Antitubercular Agents/pharmacology , Diamines/pharmacology , Mycobacterium tuberculosis/drug effects , Amino Alcohols/chemical synthesis , Antitubercular Agents/chemistry , Diamines/chemical synthesis , Microbial Sensitivity TestsABSTRACT
A series of diamines and amino alcohols derived from 1-dodecanol, 1-tetradecanol, 1,2-dodecanediol and 1,2-tetradecanediol were synthesized and tested for their antitubercular activity. Compounds 3, 8 and 9 were found to be the most active (MIC of 6.25 µg/mL). Nine other compounds displayed activity against Mycobacterium tuberculosis, with a MIC of 12.5 µg/mL.
Subject(s)
Amino Alcohols/pharmacology , Antitubercular Agents/pharmacology , Diamines/pharmacology , Mycobacterium tuberculosis/drug effects , Amino Alcohols/chemical synthesis , Antitubercular Agents/chemistry , Diamines/chemical synthesis , Microbial Sensitivity TestsABSTRACT
We report in this work the preparation and the in vitro antileishmanial activity of a series of long chains N-monoalkylated diamines and two pyridinediamine derivatives. Several compounds, tested for their in vitro antiproliferative activity against Leishmania amazonensis and Leishmania chagasi, displayed a good inhibition of parasite growth, with IC(50) below 10 microM. Compounds 10 (N-dodecyl-1,2-ethanediamine), 15 (N-decyl-1,3-propanediamine) and 20 (N-dodecyl-1,4-butanediamine) were 7.3, 2.6 and 3.6 times, respectively, more active than the reference drug amphotericin B against L. chagasi promastigote forms.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/pharmacology , Diamines/chemistry , Diamines/pharmacology , Leishmania/drug effects , Animals , Molecular StructureABSTRACT
Fluoroquinolone (FQ) has a broad spectrum of activity against several bacteria, mycobacteria, parasites, and other diseases. Moxifloxacin and gatifloxacin are a new generation of fluoroquinolone agents with improved activity against Gram-negative and positive bacteria. As lipophilicity is an important consideration in the design and activity of novel antibacterial agents, we report in this work the synthesis and biological evaluation of 12 lipophilic moxifloxacin or gatifloxacin derivatives, by reaction of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid 13 with several N-monoalkyl 1,2-ethanediamine or 1,3-propanediamine.