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Drug Res (Stuttg) 2016; 66(08): 436-443
DOI: 10.1055/s-0042-109392
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

QSAR Studies and Design of Some Tetracyclic 1,4-Benzothiazines as Antimicrobial Agents

S. Mor
1   Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India
,
S. Nagoria
1   Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India
,
A. Kumar
2   Department of Phamaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India
,
A. Kumar
3   Department of Bio & Nano Technology, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India
,
C. P. Kaushik
1   Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, India
› Author Affiliations
Further Information

Publication History

received 27 April 2016

accepted 24 May 2016

Publication Date:
07 July 2016 (online)

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Abstract

A quantitative structure-activity relationship (QSAR) analysis has been performed on a series of 20 tetracyclic 1,4-benzothiazines (1a–1t) with antimicrobial activity to explain the observed biological activity trend on structural basis. Multiple linear regression (MLR) method was employed to establish statistically significant QSAR models. The developed models are robust, predictive and free from chance correlation with good fitting ability and sufficient generalizability. These studies revealed the dominance of WHIM parameters in describing antimicrobial activity of the title compounds. Further, design of some more active compounds is presented.

Key words

antibacterial drugs - antifungal drugs - chemistry - WHIM parameters
 

  • References

  • 1 Gupta RR Phenothiazines and 1,4-benzothiazines. In: Gupta RR. (Ed.). Chemical and biomedical aspects. Vol. 4 of Bioactive molecules. Amsterdam: Elsevier; 1988: 163-260
    Google Scholar
  • 2 Shamsuzzaman DAM, Khanam H, Gatoo MA. Anticancer and antimicrobial evaluation of newly synthesized steroidal 5,6 fused benzothiazines. Arab J Chem 2014; 7: 461-468
    CrossrefPubMedGoogle Scholar
  • 3 Zieba A, Sochanik A, Szurko A et al. Synthesis and in vitro antiproliferative activity of 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts. Eur J Med Chem 2010; 45: 4733-4739
    CrossrefPubMedGoogle Scholar
  • 4 Krapcho J, Somerset NJ (Aminoalkoxy-benzylidene)-2H-benzothiazine-3(4H)-ones and related compounds. US Patent 3,715,353, 1973
    PubMed
  • 5 Gowda J, Khader AMA, Kalluraya B et al. Synthesis, characterization and pharmacological activity of 4-{[1-substituted aminomethyl-4-arylindeneamino-5-sulfanyl-4,5-dihydro-1H-1,2,4-triazol-3-yl]methyl}-2H-1,4-benzothiazin-3(4H)-ones. Eur J Med Chem 2011; 46: 4100-4106
    CrossrefPubMedGoogle Scholar
  • 6 Hirasawa A, Haruno A, Matsuzaki T et al. Effects of a new antiarrhythmic drug, SD-3212, on canine ventricular arrhythmia models. Jpn Heart J 1992; 33: 851-861
    CrossrefPubMedGoogle Scholar
  • 7 Park JS, Rhee SD, Kang NS et al. Anti-diabetic and anti-adipogenic effects of a novel selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344). Biochem Pharmacol 2011; 81: 1028-1035
    CrossrefPubMedGoogle Scholar
  • 8 Kajino M, Mizuno K, Tawada H et al. Synthesis and biological activities of new 1,4-benzothiazines. Chem Pharm Bull 1991; 39: 2888-2895
    CrossrefPubMedGoogle Scholar
  • 9 Matsuoka H, Ohi N, Mihara M et al. Antirheumatic agents: Novel methotrexate derivatives bearing a benzoxazine or benzothiazine moiety. J Med Chem 1997; 40: 105-111
    CrossrefPubMedGoogle Scholar
  • 10 Barazarte A, Lobo G, Gamboa N et al. Synthesis and antimalarial activity of pyrazolo and pyrimido benzothiazine dioxide derivatives. Eur J Med Chem 2009; 44: 1303-1310
    CrossrefPubMedGoogle Scholar
  • 11 Grandolini G, Perioli L, Ambrogi V. Synthesis of some new 1,4-benzothiazine and 1,5-benzothiazepine tricyclic derivatives with structural analogy with TIBO and their screening for anti-HIV activity. Eur J Med Chem 1999; 34: 701-709
    CrossrefPubMedGoogle Scholar
  • 12 Guleria A, Jangid DK, Gautam N et al. Synthesis and antitubercular screening of some novel 4H-1,4-benzothiazines and their sulfones under environment benign solvent free conditions as future anti-tubercular agents. Comb Chem High Throughput Screening 2015; 18: 48-52
    CrossrefPubMedGoogle Scholar
  • 13 King DJ, Wager E. Haematological safety of antipsychotic drugs. J Psychopharmacol 1998; 12: 283-288
    CrossrefPubMedGoogle Scholar
  • 14 Kumar M, Sharma K, Samarth RM et al. Synthesis and antioxidant activity of quinolinobenzothiazinones. Eur J Med Chem 2010; 45: 4467-4472
    CrossrefPubMedGoogle Scholar
  • 15 Liso G, Trapani G, Berardi V et al. Adducts of 2-aminothiophenol with acetylenic nitriles or esters and their conversion into benzothiazoles and/or 1,4-benzothiazines. J Heterocycl Chem 1980; 17: 793-796
    CrossrefPubMedGoogle Scholar
  • 16 Patmore EL, Chafetz H. Conversion of enamines to saturated amines. J Org Chem 1967; 32: 1254-1255
    CrossrefPubMedGoogle Scholar
  • 17 Sharma PR, Gupta V, Gautam DC et al. Synthesis of 7-bromo/5,6-dimethyl-4H-1,4-benzothiazines and their conversion into sulfones. Phosphorus, Sulfur Silicon Relat Elem 2003; 178: 1483-1488
    CrossrefPubMedGoogle Scholar
  • 18 Ajani OO. Functionalized 1,4-Benzothiazine: A Versatile Scaffold with Diverse Biological Properties. Arch Pharm Chem Life Sci 2012; 345: 841-851
    CrossrefPubMedGoogle Scholar
  • 19 Suresh N. Human androgen receptor inhibitors: Computational 3D QSAR studies to design lead compounds for treatment of prostate cancer. Turk J Biochem 2013; 38: 262-269
    PubMedGoogle Scholar
  • 20 Lal K, Kaushik CP, Kumar A. Antimicrobial evaluation, QSAR and docking studies of amide-linked 1,4-disubstituted 1,2,3-bistriazoles. Med Chem Res 2015; 24: 3258-33271
    CrossrefPubMedGoogle Scholar
  • 21 Mor S, Nagoria S. An efficient and convenient synthesis, characterization and antimicrobial evaluation of some new tetracyclic 1,4-benzothiazines. Synth Commun 2016; 46: 169-178
    CrossrefPubMedGoogle Scholar
  • 22 Marvin Sketch 5.10.1 Chem Axon Ltd. 1998–2012 http://www.chemaxon.com
    PubMed
  • 23 Yap CW. PaDEL-Descriptor: An open source software to calculate molecular descriptors and fingerprints. J Comput Chem 2011; 32: 1466-1474
    CrossrefPubMedGoogle Scholar
  • 24 Golbraikh A, Tropsha A. Beware of q2!. J Mol Graph Model 2002; 20: 269-276
    CrossrefPubMedGoogle Scholar
  • 25 Long W, Xiang J, Wu H et al. QSAR modeling of iNOS inhibitors based on a novel regression method: Multi-stage adaptive regression. Chemom Intell Lab Syst 2013; 128: 83-88
    CrossrefPubMedGoogle Scholar
  • 26 Agrawal VK, Sharma R, Khadikar PV. QSAR studies on antimalarial phenyl analogues and their Nω-Oxides. Bioorg Med Chem 2002; 10: 1361-1366
    CrossrefPubMedGoogle Scholar
  • 27 Todeschini R, Lasagni M, Marengo EJ. New molecular descriptors for 2D- and 3D-structures. Theory. J Chemom 1994; 8: 263-272
    CrossrefPubMedGoogle Scholar
  • 28 Todeschini R, Gramatica P. New 3D molecular descriptors: The WHIM theory and QSAR applications. Perspect Drug Discov Des 1998; 9–11: 355-380
    PubMedGoogle Scholar
  • 29 Todeschini R, Gramatica P. The Whim theory: New 3D molecular descriptors for QSAR in environmental modeling. SAR QSAR Environ Res 1997; 7: 89-115
    CrossrefPubMedGoogle Scholar
  • 30 Gramatica P. Principles of QSAR models validation: internal and external. QSAR Comb Sci 2007; 26: 694-701
    CrossrefPubMedGoogle Scholar
  • 31 Furusjo E, Svenson A, Rahmberg M et al. The importance of outlier detection and training set selection for reliable environmental QSAR predictions. Chemosphere 2006; 63: 99-108
    CrossrefPubMedGoogle Scholar