In the title compound, C9H13N3O4, an ester of the anti-infection drug secnidazole, the dihedral angle between the nitroimidazole mean plane (r.m.s. deviation = 0.028 Å) and the pendant acetate group is 43.17 (11)°. In the crystal, inversion dimers linked by pairs of C—H⋯O interactions generate R
2(10) loops and further C—H⋯O hydrogen bonds link the dimers into  chains. Weak aromatic π–π stacking interactions with a centroid–centroid distance of 3.7623 (11) Å are also observed.
The title phenylhydrazine derivative, C16H16N2O4, has a crystallographically imposed centre of symmetry. Except for the methyl group, all non-H atoms are almost coplanar (r.m.s. deviation = 0.0095 Å). Intramolecular O—H⋯N hydrogen bonds are observed, generating S(6) graph-set ring motifs.
In the molecule of the title difluorobenzamide derivative, C10H7F2NO, the angle formed by the least-squares mean line through the prop-2-ynyl group [maximum deviation = 0.011 (3) Å] and the normal to the benzene ring is 59.03 (7)°. In the crystal, molecules are linked via N—H⋯O and C—H⋯F hydrogen bonds into layers parallel to the ac plane.
The asymmetric unit of the title compound, C10H6N2S2, contains two crystallographically independent but conformationally similar molecules. The fused thiophene ring cores are almost planar [maximum deviation = 0.027 (3) Å] with the thiophene rings forming dihedral angles of 0.5 (4)° in one molecule and 1.91 (4)° in the other. The crystal packing is stabilized only by van der Waals interactions.
The derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application.
A new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br2/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3–9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and β-glucuronidase and α-glucosidase inhibitory activities. Compound 3 (IC50 = 56.26 ± 3.18 μM) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50 = 105.9 ± 1.1 μM). Compounds 8a (IC50 = 13.2 ± 0.34 μM) and 8b (IC50 = 14.1 ± 0.28 μM) found as potent inhibitor of α-glucusidase several fold more active than the standard acarbose (IC50 = 841 ± 1.73 μM). Most promising results were obtained in β-glucuronidase enzyme inhibition assay. Compounds 5 (IC50 = 0.13 ± 0.019 μM), 6 (IC50 = 19.9 ± 0.285 μM), 8a (IC50 = 1.2 ± 0.0785 μM) and 9 (IC50 = 0.003 ± 0.09 μM) showed a potent inhibition of β-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM).
Synthesis, characterization, and in vitro biological activity of a series of thieno[2,3-b]thiophene have been investigated.
Thienothiophene; Oxazole; Imidazole; Thiazole; Bisheterocycles; β-glucuronidase inhibition; α-glucosidase inhibition; DPPH radical scavenging activity; Ctotoxicity; Cancer cell line
In the title compound, C16H17NO3S, a thiophene derivative with amino phenyl, acetyl, methyl and ethyl carboxyl susbtituents attached to a central thiophene ring, the phenyl and thiophene rings form a dihedral angle of 36.92 (9) Å. The molecular conformation is stabilized by an intramolecular N—H⋯O hydrogen bond, which forms an S(6) ring motif.
In the molecule of the title compound, C13H14O4, the benzene ring forms dihedral angles of 18.60 (7) and 81.36 (8)° with the two arms of the malonate moiety. The crystal structure features C—H⋯O interactions, which form chains running parallel to the b axis.
In the molecule of the title compound, C7H9N3O3, the nitro and carbonyl groups are tilted with respect to the imidazole ring by 9.16 (6) and 65.47 (7)°, respectively. Neighbouring chains are linked via C—H⋯N and C—H⋯O hydrogen bonds forming two-dimensional slab-like networks lying parallel to (01-1).
In the title compound, C16H16N2O3·H2O, the dihedral angle between the benzene rings is 30.27 (7)°. In the crystal, the components are linked by N—H⋯O, O—H⋯O and C—H⋯O interactions into a three-dimensional network.
In the title benzoylhydrazide derivative, C17H18N2O, the dihedral angle between the benzene rings is 88.45 (8)° and the azomethine double bond adopts an E conformation. In the crystal, molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming a chain along the b axis.
In the title compound, C14H10ClNOS, the dihedral angle between the benzothiazole ring system and the methoxy-substituted benzene ring is 8.76 (16)°. In the crystal, molecules are stacked in columns along the c axis and no significant intermolecular interactions are observed.
In the title compound, C24H24N2O3S, the phenyl rings form dihedral angles of 55.65 (11) and 79.60 (11)° with the plane of the thiophene ring. The molecular conformation is stabilized by an intramolecular N—H⋯O hydrogen bond, generating an S(6) ring motif. In the crystal, centrosymmetrically related molecules are linked into dimers by two pairs of C—H⋯O interactions.
The asymmetric unit of the title compound, 2C2H6N5
2−, contains two 3,5-diamino-4H-1,2,4-triazolium cations and one squarate dianion. The squaric acid molecule donated one H atom to each of the two 3,5-diamino-1,2,4-triazole molecules at their N atoms. The squaric acid dianion has four C—O bonds which are shorter than a normal single C—O bond (1.426 Å) and are slightly longer than a normal C=O bond (1.23 Å), which indicates the degree of electron delocalization in the dianion. In the crystal, the cations and dianions are linked by N—H⋯N and N—H⋯O hydrogen bonds into a three-dimensional network.
In the title hydrazone derivative, C15H13ClN2O2, the dihedral angle between the benzene rings is 2.36 (2)°. An intramolecular N—H⋯O hydrogen bond is present. In the crystal, N—H⋯O and C—H⋯O hydrogen bonds link the molecules into chains running parallel to the b axis.
In the title hydrazone derivative, C15H14N2O5, the benzene rings are twisted by 7.55 (8)° with respect to each other. The azomethine double bond adopts an E conformation. The molecular structure is stabilized by intramolecular O—H⋯N and N—H⋯O hydrogen bonds, generating S6 ring motifs. In the crystal, molecules are linked into a three-dimensional network by O—H⋯O hydrogen bonds.
In the title compound, C29H21O3P, a coumarin-substitued ylid, the P atom is linked to three benzene rings and a planar coumarin moiety via a methylenecarbonyl group. The bond lengths in the P=C–C=O fragment clearly indicate a delocalized system involving the olefinic and carbonyl bonds. The molecular structure is stabilized by an intramolecular C—H⋯O interaction that results in an S7 graph-set ring motif. In the crystal, molecules are linked into a three-dimensional framework by C—H⋯O hydrogen bonds.
The title molecule, C10H10N4O2, is almost planar and adopts an E configuration of the azomethine [C=N = 1.298 (2) Å] double bond. The benzene ring is attached to an essentially planar (r.m.s. deviation = 0.0226 Å) amidine moiety (N=CN/Me2), the dihedral angle between the two mean planes being 18.42 (11)°. The cyano group lies in the plane of the benzene ring [the C and N atoms deviating by 0.030 (3) and 0.040 (3) Å, respectively], while the nitro group makes a dihedral angle 5.8 (3)° with the benzene ring. There are two distinct intermolecular hydrogen bonds, C—H⋯O and C—H⋯N, that stabilize the crystal structure; the former interactions result in centrosymmetric dimers about inversion centers resulting in ten-membered rings, while the later give rise to chains of molecules running parallel to the b axis.
Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures.
Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2–5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1–7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 μg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay.
Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs.
Oxymetholone; Anabolic steroid; Biotransformation; de novo Hydroxylation; Immunomodulation; T-Cell proliferation inhibition; Anti-inflammation; Inhibition of reactive oxygen species production; 3T3 Fibroblast cells
In the title molecule, C16H14N4O4, the quinazoline ring is substantially planar (r.m.s. deviation = 0.0129 Å) and forms a dihedral angle of 2.73 (8)° with the benzene ring. The conformation of the molecule is stabilized by an intramolecular C—H⋯N hydrogen bond. In the crystal, molecules are linked into chains running parallel to the b axis by C—H⋯O hydrogen bonds. In addition, π–π stacking is observed between dimethoxy-substituted and nitro-substituted benzene rings, with centroid–centroid distances in the range 3.6438 (10)–3.7148 (10) Å.
The molecule of the title compound, C14H11ClN2O2 adopts an E conformation of the azomethine double bond and the dihedral angle between the benzene rings is 38.96 (13)°. In the crystal, molecules are linked by N—H⋯O and O—H⋯O (with the ketone O atom as acceptor) and C—H⋯O (with the hydroxy O atom as acceptor) hydrogen bonds, forming a three-dimensional network.
In the title compound, C16H15N3O, the dihedral angle between the indole ring system (r.m.s. deviation = 0.020 Å) and the phenyl ring is 14.49 (9)°. The molecular conformation is supported by an intramolecular C—H⋯O interaction, which closes an S(7) ring. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R
The molecule of the title compound, C16H16N2O4, adopts an E conformation about the azomethine C=N double bond. The dihedral angle formed by the benzene rings is 18.88 (9)°. The molecular conformation is stabilized by an intramolecular O—H⋯N hydrogen bond, which forms an S(6) ring. In the crystal, the molecules are linked into chains parallel to  by N—H⋯O hydrogen bonds. The chains are further connected into a three-dimensional network by π–π stacking interactions with centroid–centroid distances of 3.6538 (10) and 3.8995 (11) Å.
The title compound, C15H14N2O4 adopts an E conformation about the azomethine double bond. Intramolecular N—H⋯O and O—H⋯N hydrogen bonds generate S(6) rings and help to establish the molecular conformation. The dihedral angle between the benzene rings is 17.84 (10)°. In the crystal, molecules are linked by O—H⋯O and C—H⋯O hydrogen bonds into a two-dimensional network with a herring-bone pattern arranged parallel to the bc plane.
In the title compound, C15H14N2O5, the central amide C—C(=O)—N—C unit forms dihedral angles of 28.17 (13) and 26.47 (13)° with the two benzene rings, whereas the two benzene rings are almost coplanar, making a dihedral angle of 4.52 (13)°. The two methoxy and the nitro substituents are almost coplanar with their attached benzene rings, with C—O—C—C torsion angles of −1.3 (4) and −4.6 (4)°, and an O—N—C—C torsion angle of 17.1 (3)°. In the crystal, molecules are linked via C—H⋯O and N—H⋯O interactions, forming a tape running along the b axis.
In the title compound, C16H14ClNO3S, the dihedral angle between the almost-planar benzothiazole ring system [maximum deviation = 0.012 (3) Å] and the aromatic ring of the trimethoxyphenyl group is 15.56 (6)°. In the crystal, the molecules are arranged into layers parallel to the bc plane, held together only by weak van der Waals forces.