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Drug Res (Stuttg) 2015; 65(1): 5-8
DOI: 10.1055/s-0033-1364001
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Synthesis and Biological Activity of Piperazine Derivatives of Phenothiazine

A. M. Amani
1   Department of Chemistry, Shiraz University of Technology, Shiraz, Iran
› Author Affiliations
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Publication History

received 13 December 2013

accepted 29 December 2013

Publication Date:
27 January 2014 (online)

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Abstract

Some novel piperazine derivatives of phenothiazine were synthesized. The structures of the synthesized compounds were characterized by elemental analysis, FT-IR, 1H- and 13C-NMR and Mass Spectroscopy. The compounds were evaluated for antibacterial, antifungal and antitubercular activity by cup plate, disc diffusion and Lowenstein-Jensen medium methods respectively. All the compounds showed good antibacterial activity against Staphylococcus aureus and Bacillus subtilis. Compound V showed equipotent antibacterial activity with streptomycin standard and showed better antibacterial activity against gram positive bacteria profile than gram negative bacteria. Zone of inhibition was not found for the compounds against Escherichia coli and Pseudomonas aeruginosa. All the compounds exhibited good antifungal activity against Aspergillus species and no activity against Candida albicans. All the compounds at a concentration of 100, 10 and 1 µg/L showed inhibition against the growth of Mycobacterium tuberculosis.

Key words

phenothiazine derivatives - antibacterial - antifungal - antitubercular
 

  • References

  • 1 Jaszczyszyn A, Gsiorowski K, Switek P et al. Chemical structure of phenothiazines and their biological activity. Pharmacological Reports 2012; 64: 16-23
    CrossrefPubMedGoogle Scholar
  • 2 Borbely AA, Hinkkanen ML. Synthesis and antifungal activity of some substituted phenothiazines and related compounds. Mod Pharmacol Toxicol 1979; 16: 403-426
    PubMedGoogle Scholar
  • 3 Reld WR, Wright JR, Kollofe HG et al. Synthesis and antimicrobial activity of 10 N{[(Aryl)-amino]-methyl}3-methoxy-10,10adihydro-4a-H-phenothiazine-9-carboxylic acid. J Am Chem Soc 1948; 70: 3100
    CrossrefPubMedGoogle Scholar
  • 4 Foye O. Principles of Medicinal Chemistry. 3rd, Lippincott Williams & Wilkins Publishers 2012;
    PubMedGoogle Scholar
  • 5 Mosnaim AD, Ranade VV, Wel ME et al. Phenothiazine molecule provides the basic chemical structure for various classes of pharmacotherapeutic agents. Am J Ther 2006; 13: 261-273
    CrossrefPubMedGoogle Scholar
  • 6 Shibl AM, Hammouda Y, Al-Sowaygh I. Comparative effects of selected phenothiazine tranquilizers and antihistaminics on bacterial cells and possible interactions with antibiotics. J Pharm Sci 1984; 73: 841-843
    CrossrefPubMedGoogle Scholar
  • 7 Tilak SR, Tyagi R, Goel B et al. Synthesis and Anti-Inflammatory Activity of Some Potential Cyclic Phenothiazines. Indian drugs 1998; 35: 221
    PubMedGoogle Scholar
  • 8 Dominguez JN, Lopez S, Charris J et al. Synthesis and antimalarial effects of phenothiazine inhibitors of a Plasmodium falciparum cysteine protease. J Med Chem 1997; 40: 2726-2732
    CrossrefPubMedGoogle Scholar
  • 9 Lin G, Midha KK, Hawes EM. Synthesis of the piperidinone metabolites of piperidine type phenothiazine antipsychotic drugs via ruthenium tetroxide oxidation. J Heterocycl Chem 1991; 28: 215
    CrossrefPubMedGoogle Scholar
  • 10 Raval J, Desai KK. Synthesis and antimicrobial activity of new triazolopyridinyl phenothiazines. ARKIVOC 2005; xiii: 21
    PubMedGoogle Scholar
  • 11 Viveros M, Amaral L. Design, synthesis, characterization and antitubercular activity of some 2-heterocycle-substituted phenothiazines. Int J Antimicrob Ag 2001; 17: 225
    CrossrefPubMedGoogle Scholar
  • 12 Kristiansen AL. Phenothiazines: an alternative to conventional therapy for the initial management of suspected multidrug resistant tuberculosis. A call for studies. Int J Antimicrob Ag 2000; 14: 173
    CrossrefPubMedGoogle Scholar
  • 13 Motohasho N, Kawase M, Saito S et al. Antitumor potential and possible targets of phenothiazine-related compounds. Curr Drug Targets 2000; 1: 237-245
    CrossrefPubMedGoogle Scholar
  • 14 Motohashi N, Kawase M, Saito S et al. Synthesis and biological activity of N-acylphenothiazines. Int J Antimicrob Ag 2000; 14: 203-207
    CrossrefPubMedGoogle Scholar
  • 15 Leancer D, Mitscher LA. Organic chemistry of drug synthesis 2000; 1: 372-392
    PubMed
  • 16 Madrid PB, Polgar WE, Tolla L et al. Synthesis and antitubercular activity of phenothiazines with reduced binding to dopamine and serotonin receptors. Bioorg Med Chem Letters 2007; 17: 3014-3017
    CrossrefPubMedGoogle Scholar
  • 17 Shanmugakumar SD, Amerjothy S, Balakrishna K. Pharmacognostical, antibacterial and antifungal potentials of the leaf extracts of Pithecellobium dulce Benth. Phcog Mag 2006; 2: 163-167
    PubMedGoogle Scholar
  • 18 George S, Parameshwaran MK, Chakraborti AR et al. Synthesis and evaluation of the biological activities of some 3-{[5-6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2 H-indol-2-one derivatives. Acta Pharma 2008; 58: 119-129
    PubMedGoogle Scholar
  • 19 Cambau E, Truffot-Pernot C, Boulahbal F et al. Mycobaterial growth indicator tube versus the proportion method on Lowenstein-Jensen medium for antibiotic susceptibility testing Mycobaterium tuberculosis. Clin Micro Inf Dis 2000; 12: 938-942
    PubMedGoogle Scholar