of DHFR of M. tuberculosis reveals opportunities for the design of novel tuberculosis drugs . DHFR catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, and this is essential for the synthesis of thymidylate, purines, and several amino acids. Inhibition of the enzyme’s activity leads to the arrest of DNA synthesis and cell death. Hence, the inhibitors of this enzyme may control the population of this mycobacterium. The crystal structure of Staphylococcus Gyrase in complex with novobiocin (PDB code: 4URO) was used in docking studies to describe the antibacterial role . DNA gyrase of bacteria is an essential topoisomerase that supercoils DNA through a process of strand breakage/resealing and DNA wrapping . DNA gyrase is also the target for quinolone-based antibacterial agents which act by subverting the enzyme into a DNA damaging agent. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase activity. The anti-melanoma activity was predicted using the interaction data between CR2 and Human B-Raf Kinase (PDB code: 3C4C), which is co- crystallized with an inhibitor named PLX4720 . The binding modes of the compound with the protein targets were studied using a well- known generic algorithm based iGemDock v2. 1. The pharmacological interactions between the compound and the targets were studied for the better understanding of ligand binding mechanisms. iGemDock is an interactive graphical generic evolutionary method for molecular docking for computing ligand conformations and orientations relative to the active site of target proteins . The binding sites for the three targets were prepared by considering a radius of 8 Å with co-crystal ligands as the center. The co-crystal ligands were also included in the docking procedure to check the efficacy of the protocol followed. All ligands were prepared for the correctness of their structures
analogue of compound (I). The compound (1-phenylsulfonyl- 1H-indol-2-yl)(thiophen-2-yl)methanone (ULINEJ; Kamala- Kumar et al., 2011), which crystallizes in space group P1, is the closest analogue of compound (II). The packing of compounds (I) and (II) feature C—H O and C—H S interactions, but the related structures exhibit C—H O and C—H interactions. In the latter structures, the sulfonyl-bound phenyl ring is almost orthogonal to the indole ring system, making dihedral angles of 84.89 (7) and 54.91 (11) , respectively,
In the crystal array three intramolecular interactions C3—H3···F1 (2.969 Å), C16—H16···F3 (3.029 Å) and C26— H26···F2 (2.989 Å) of type hydrogen bonds are observed, and in the crystal packing intermolecular contacts of non- classical hydrogen bonds are observed growing along the a, b and c axes, resulting in a complex supramolecular array (Fig. 2).
The indole derivatives are known to exhibit anti-bacterial and anti-tumour activities (Okabe & Adachi, 1998; Schollmeyer et al., 1995). We herein report the crystal structure of the title compound (I), (Fig. 1). The geometric parameters of (I) are comparable with the reported similar structures (Chakkaravarthi et al., 2007, 2008). The phenyl ring forms a dihedral angle of 75.07 (8)° with the indole ring system. The five-membered (N1/C7/C12–C14) and six-
Indole derivatives exhibit antitumour (Andreani et al., 2001) and antiviral (Kolocouris et al., 1994) activities. The molecular structure of the title compound is illustrated in Fig. 1. The geometric parameters of the title molecule agree well with the reported similar structures (Chakkaravarthi et al. 2007, 2008). The torsion angles O1—S1—N1—C7 and O2—S1—N1—C14 [-48.0 (3)° and 38.3 (3)°, respectively] indicate the syn-conformation of the sulfonyl moiety.
chromatography. After the reaction was complete, the solvent was removed in vacuo and the residue was separated by column chromatography (silica gel, petroleum ether/ethyl acetate = 5:1) to give the title compound, (I). 20 mg of (I) was dissolved in 15 ml chloroform, the solution was kept at room temperature for 15 d by natural evaporation to give colorless single crystals of (I), suitable for X-ray analysis. M.p. 487–488 K; IR (KBr, cm −1 ): 3493 (N—H), 1694, 1682
(0.33 g, 2.43 mmol) and benzyl chloride (0.20 g, 1.58 mmol) were added and the reaction mixture was stirred at room temperature for 12 h. after completion of starting material (monitored by TLC), the reaction mass was poured over crushed ice containing Conc. HCl (3 ml) and extracted with ethyl acetate (20 ml). The combined organic extracts were washed with water (3 ml), brine solution (3 ml) and dried (Na 2 SO 4 ). Removal of solvent followed by recrystallization of
The total puckering amplitudes (Cremer & Pople, 1975) of the rings A, B, C give a quantitative evaluation of puckering and asymmetry parameters. Ring A is in a half-chair conformation, with lowest asymmetry parameter (Nardelli, 1983) C 2 [C10] = 0.0047 (8) and puckering parameters q 2 =
The H atoms were positioned geometrically and were treated as riding on their parent atoms, with aromatic CÐH distances of 0.93 AÊ, methylene CÐH distances of 0.98 AÊ, ethylene CÐH distances of 0.97 AÊ and NÐH distances of 0.86 AÊ. U iso = 1.5U eq (C) for methyl H
The total puckering amplitudes (Cremer & Pople, 1975) of rings A, B and C give a quantitative evaluation of the puck- ering and asymmetry parameters. Ring A is in a half-chair conformation, with the lowest asymmetry parameter (Nardelli, 1983) C 2 [C10 = 0.0039 (7)]. Pyrrolidine ring B is
and φ = 180 (15)°. The indole ring system (N1/C1–C7/C14) is essentially planar, with the maximum deviations of 0.014 (2) Å for N1 and 0.012 (3) Å for C5. The phenyl (C8–C13) and 1,3-thiazolidine (S1/N3/C16/C17/C19) rings are inclined at the dihedral angles of 56.14 (15) and 57.03 (12) °, respectively, to the indole ring system. The torsion angle of the N3– N2–C15–C14 bridge between the indole ring and the thiazolidine ring system is -165.8 (2) °.
Heterocycles containing the 1,3-thiazole ring system exhibit a wide spectrum of biological activities, including acting as antiviral and antifungal agents, and this system has been identified as a central structural element of a number of biologically active natural products (Zabriskie et al., 1988) and of pharmacologically active compounds (Metzger, 1984). Thiadiazole and its derivatives are also used for biological activities such as antiviral, antibacterial, antifungal and anti- tubercular. Indole and its derivatives form a class of toxic recalcitrant N-heterocyclic compounds that are considered as pollutants (Florin et al., 1980). Azo dyes have wide applic- ability as optical materials and their structures have also attracted considerable attention (Biswas & Umapathy, 2000). To the best of our knowledge, few structures of azoindole derivatives have been reported to date (Bruni et al., 1995; Seferog˘lu et al., 2006a,b,c; Seferog˘lu et al., 2006). This study was undertaken in order to ascertain the crystal structure of (I).
The title compound was synthesized by reaction of iodine (942 mg, 3.70 mmol) with N-(2-(2-hydroxybut-3-yn-2- yl)phenyl-4-methyl)benzenesulfonamide (584.9 mg,1.854 mmol) in the presence of methanol (20 ml) as a solvent. The resulting mixture was stirred for 6 h at 60°C. The reaction was then quenched by adding a saturated aq. solution of Na 2 S 2 O 3 and extracted with ethyl acetate (3×20 mL). The combined organics were then washed with aq. NaHCO 3 and
ring. The supramolecular aggregation is completed by weak C—H interactions of the methylene and phenyl groups with the benzene and pyrrole rings of the indole ring system. The methyl groups of the trimethylsilyl unit are equally disordered over two sets of sites.
Data collection: CrystalClear (Rigaku/MSC, 2005); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).
Azo derivatives are used extensively in analytical chemistry and in the dyestuff industry as metallochromic and acid–base indicators (Rau, 1990; Zollinger, 1987). They are also used in the fields of nonlinear optics and optical data storage (Clark & Hester, 1991; Bach et al., 1996; Taniike et al., 1996). Azo dyes have wide applicability as optical materials and so their structures have also attracted considerable attention (Biswas & Umapathy, 2000; Willner & Rubin, 1996). Indole and its derivatives form a class of toxic recalcitrant N-heterocyclic compounds that are considered as pollutants (Florin et al., 1980; Ishiguro & Sugawara, 1978), and aryl azoindoles form yellow or orange dyes (Aldemir et al., 2003). Many azo-dye breakdown products are carcinogenic, toxic or mutagenic to life (Ochiai et al., 1986). Although there are many publications on the industrial applications of azo dyes (Tsuda et al., 2000), to the best of our knowledge the structures of azoindole-type derivatives have not been reported to date. This study was undertaken in order to ascertain the crystal structure of the title phenyldiazenylindole dye, (I).
ring system. The molecular structure is stabilized by a weak intramolecular C—H O hydrogen bond. The crystal struc- ture exhibits weak intermolecular C—H interactions and – interactions between the indole groups [centroid– centroid distance between the five-membered and six- membered rings of the indole group = 3.7617 (18) A ˚ ].