Crystal structure and docking studies of hexahydrocycloocta[b]pyridine-3-carbonitriles

R Vishnupriya, A.V.K.M. Kowsalyadevi, Janakiraman Suresh, S Maharani, R Ranjith Kumar

Abstract


The crystal structures of two new isomorphous pyridine structures, 2-ethoxy-4-(2-flurophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ia) and 2-methoxy-4-(4-isopropylphenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine-3-carbonitrile (Ib) were elucidated by single crystal X ray diffraction. Compound (Ia) C20H21FN2O, crystallizes in the monoclinic system, space group P21/nwith a = 7.0738 (3) Å, b = 17.3519(8) Å, c = 14.4239 (7) Å, b = 91.837 (2)° and Z = 4. The compound (Ib), C22H25N2O, crystallizes in the same crystal system as compound (Ib), space group P21/c with a = 9.7123(6) Å, b = 20.6046(9) Å, c = 10.4657(6) Å,  b = 117.208 (3)° and Z = 4. The central heterocyclic ring adopts a planar conformation and the cyclooctane ring adopts a twisted boat chair conformation in both (Ia) and (Ib).   The synthesized compounds were screened for their anti-tuberculosis activity and were used to identify lead structures through docking studies, by automated docking. This approach was used to determine the orientation of inhibitors bound in the active site with the enzyme N-acetyl-gamma-glutamyl-phosphate reductase that is involved in arginine biosynthesis in M. tuberculosis (MtbAGPR). Details of the preparation, crystal structure determination, intra and inter molecular interactions of the compounds and their docking studies are given.


Keywords


Twisted boat Chair conformation, Intermolecular interactions, Chain motif, Antituberculosis activity, Molecular docking.

References


Allen FH 2002 The Cambridge Structural Database: a quarter of a million crystal structures and rising Acta Cryst B 58 380-388

Allen FH, Kennard O, Watson DG, Brammer L, Orpen AG & Taylor R 1987 J Chem Soc Perkin Trans. 2 S1–19

Balzani S & Campagna S 2007 Photochemistry and Photophysics of Coordination Compounds I & II (Topics in Current Chemistry), vol. 280-281. Berlin: V. Springer Verlag

Bernstein J, Davis RE, Shimoni L & Chang NL 1995 Patterns in Hydrogen Bonding: Functionality and Graph Set Analysis in Crystals. Angew Chem Int Ed Engl 34 1555-1573

Black SN, Davey R J, Slawin AMZ & Williams DJ 1992 Acta Cryst C 48 323-325

Bolte M 1998 3-Methoxy-2,4,6-triphenylpyridine at 173K Acta Cryst C 54 132-134

Bruker 2004 APEX2 and SAINT. Bruker AXS Inc, Madison, Wisconsin, USA

Cherney LT, Cherney MM, Garen CR, Chunying Niu , Fatemeh Moradian & Michael James NG 2007 Crystal Structure of N-acetyl-g-glutamyl-phosphate Reductase from Mycobacterium tuberculosis in Complex with NADP+ J Mol Biol 367 1357 - 1369

DeLano WL 2002 The PyMOL Molecular Graphics System . DeLanoScientific, San Carlos, CA, USA

Desai B , Sureja D , Naliapara Y , Shah A & Saxena AK 2001 Synthesis and QSAR studies of 4-substituted phenyl-2,6-dimethyl-3, 5-bis-N-(substituted phenyl)carbamoyl-1,4-dihydropyridines as potential antitubercular agents. Bioorg Med Chem 9 1993

Errey JC & Blanchard JS 2005 Functional characterization of a novel ArgA from Mycobacterium tuberculosis. J Bacteriol 187 3039-3044

Farrugia LJ 1997 ORTEP-3 for windows-a version of ORTEPIII with a graphical user interface (GUI). J Appl Cryst 30 568

Fun HK, Yeap CS, Ragavan RV, Vijayakumar V & Sarveswari S 2010 4,5,6,7,8,9-Hexahydro-2H-cycloocta[c]pyrazol-1-ium-3-olate Acta Cryst E 66 o3019

Goldman DS 1954 On the mechanism of action of isonicotinic acid hydrazide J Am Chem Soc 76 2841

Goodsell DS, Morris GM & Olson AJ 1998 Automated docking of flexible ligands: Applications of autodock. J Mol Recog 9 1-5

Gordhan BG, Smith DA, Alderton H, McAdam RA, Bancroft GJ & Mizrahi V 2002 Construction and phenotypic characterization of an auxotrophic mutant of Mycobacterium tuberculosis defective in L-arginine biosynthesis. Infect Immun 70 3080-3084

Granich R, Wares F, Suvanand S & Chauhan LS 2003 Tuberculosis control in India. Lancet Infect Dis 3 535-536

Hannon MJ & Childs LJ 2006 Helices and Helicates: Beautiful Supramolecular Motifs with Emerging Applications. Supramol Chem 16 7-22

Hussain Z, Fleming FF, Norman RE & Chang SC 1996 Acta Cryst C 52 1010-1012

Kaes C, Katz A & Hosseini MW 2000 Bipyridine: The Most Widely Used Ligand. A Review of Molecules Comprising at Least Two 2,2’- Bipyridine Units. Chem 100 3553-3590

Patel UH, Dave CG, Jotani MM & Shah HC 2002a 1,3-Dimethyl-2-oxo-4,6-diphenyl-1,2,3,4-tetrahydropyridine-3-carbonitrile. Acta Cryst C 58 o191-o192

Perez-Medina LA, Merriella RP & McElvain SM 1947 J Am Chem Soc 69 2574-2579

Quail JW, Doroud A, Pati HN, Das U & Dimmock JR 2005 (E,E)-2-(4-Fluorophenylmethylene)-6-(4-Nitrophen-ylmeThylene)Cyclohexanone. Acta Crystallographica E 61 o1774-o1776

Ramesh P, Subbiahpandi A, Thirumurugan P, Perumal PT & Ponnuswamy MN 2009 Acta Cryst E 65 o450

Ramesh P, Sundaresan SS, Thirumurugan P, Perumal PT & Ponnuswamy MN 2009 Acta Cryst E 65 o996-o997

Schalley CA, Lützen A & Albrecht M 2004 Approaching Supramolecular Functionality Chem Eur J 10 1072-1080

Sheldrick GM 2008 A short history of SHELX. Acta Cryst A 64 112-122

Smith AP, Fraser CL, McCleverty JA & Meyer TJ 2004 Comprehensive Coordination Chemistry II Vol 1. Oxford: Elsevier

Spek AL 2009 Structure validation in chemical crystal-lography Acta Cryst D 65 148-155

Suresh J, Suresh Kumar R, Perumal S & Natarajan S 2007 1'-Methylcyclooctane-1-spiro-3'-pyrrolidine-2'-spiro-3''-indoline-2,2''-dione and 1,1'-dimethylpiperidine-3-spiro-3'-pyrrolidine-2'-spiro-3''-indoline-2'',4-dione Acta Cryst C 63 o538-o542

Ubiali D, Pagani G, Pregnolato M, Piersimoni C, Munoz JP, Gascon AR & Terreni M 2002 New N-alkyl-1, 2-dihydro-2-thioxo-3-pyridine carbothioamides as antituberculous agents with improved pharmacokinetics. Bioorg Med Chem Lett 12 2541

Winder FG & Collins P 1969 The effect of isoniazid on nicotinamide nucleotide concentrations in tubercle bacilli. A correction and further observations. Am Rev Respir Dis 100 101

Wolf LK 2009 Digital Briefs C&EN 87 31

Xiong Y, Gao WY, Deng KZ, Chen HX & Wang SJ 2007 5,6-dihydroxy- 1,2,3,13- tetramethoxy -6,7-dimethyl- 5,6,7,8 – tetrahydrobenzo [3,4] cycloocta [1,2-f] [1,3] – benzodioxol-5-yl benzoate sesquihydrate Acta Cryst E 63 o333-o334


Full Text: PDF

Refbacks

  • There are currently no refbacks.


Copyright © 2017 Lorem Ipsum Press