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Design, synthesis, and antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton

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Abstract

Herein we report a feasible study concerning the design, synthesis, and in vitro antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton. The reaction pathway is efficient and straight, involving the direct N-acylation of diazine with homodrimane sesquiterpenoids bearing acyl chlorides or organic acids functionality. A reliable explication and a feasible reaction mechanism for the obtained compounds are presented. The in vitro antimicrobial activity of the homodrimane sesquiterpenoids with and without diazine skeleton has been evaluated. All the tested compounds have an excellent antibacterial activity against Gram-positive strains S. aureus and B. cereus. SAR correlations concerning antimicrobial activity are reported.

Graphical Abstract

The design, synthesis, and in vitro antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton are described. Antimicrobial tests prove that some homodrimane sesquiterpenoids have an excellent biological activity.

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References

  • Abdel-Aziz M, Bdel-Rahman HMA (2010) Synthesis and anti-mycobacterial evaluation of some pyrazine-2-carboxylic acid hydrazide derivatives. Eur J Med Chem 45:3384–3388

    Article  CAS  PubMed  Google Scholar 

  • Allouche N, Apel C, Martin MT, Dumontet V, Guéritte F, Litaudon M (2009) Cytotoxic sesquiterpenoids from Winteraceae of Caledonian rainforest. Phytochemistry 70:546–553

    Article  CAS  PubMed  Google Scholar 

  • Amr AE, Nermien MS, Abdulla MM (2007) Synthesis, reactions, and anti-inflammatory activity of heterocyclic systems fused to a thiophene moiety using citrazinic acid as synthon. Monatsh Chem 138:699–707

    Article  CAS  Google Scholar 

  • Balan AM, Florea O, Moldoveanu C, Zbancioc G, Iurea D, Mangalagiu II (2009) Diazinium salts with dihydroxyacetophenone skeleton: syntheses and antimicrobial activity. Eur J Med Chem 44:2275–2279

    Article  CAS  PubMed  Google Scholar 

  • Ballell L, Field RA, Chung GAC, Young RJ (2007) New mercaptopyrazolo[3,4-d]pyrimidine derivatives as anti-mycobacterial agents. Bioorg Med Chem Lett 17:1736–1740

    Article  CAS  PubMed  Google Scholar 

  • da Silva YKC, Augusto CV, Barbosa MLD, Melo GMD, de Queiroz AC, Dias TDMF, Bispo W, Barreiro EJ, Lima LM, Alexandre-Moreira MS (2010) Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates. Bioorg Med Chem 18:5007–5015

    Article  PubMed  Google Scholar 

  • de Castro S, Familiar O, Andrei G, Snoeck R, Balzarini J, Camarasa MJ, Velázquez S (2011) From beta-amino-gamma-sultone to unusual bicyclic pyridine and pyrazine heterocyclic systems: synthesis and cytostatic and antiviral activities. ChemMedChem 6:686–697

    Article  PubMed  Google Scholar 

  • do Céu de Madureira M, Martins AP, Gomes M, Paiva J, Proença da Cunha A, do Rosário V (2002) Antimalarial activity of medicinal plants used in traditional medicine in S. Tomé and Príncipe island. J Ethnopharmacol 81:23–29

    Article  PubMed  Google Scholar 

  • Ferreira SB, Kaiser CR (2012) Pyrazine derivatives: a patent review (2008 present). Expert Opin Ther Pat 22:1033–1051

    Article  CAS  PubMed  Google Scholar 

  • Fujiwara N, Nakajima T, Ueda Y, Fujita H, Kawakami H (2008) Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation. Bioorg Med Chem 16:9804–9816

    Article  CAS  PubMed  Google Scholar 

  • Giles D, Roopa K, Sheeba FR, Gurubasavarajaswamy PM, Divakar G, Vidhya T (2012) Synthesis pharmacological evaluation and docking studies of pyrimidine derivatives. Eur J Med Chem 58:478–484

    Article  CAS  PubMed  Google Scholar 

  • Grahman PL (2001) An introduction to medicinal chemistry, 2nd edn. Oxford University Press, New York

    Google Scholar 

  • Greenwood D, Finch R, Davey P, Wilcocs M (2007) Antimicrobial chemotherapy, 5th edn. Oxford University Press, New York

    Google Scholar 

  • Jansen BJM, de Groot A (2004) Occurrence, biological activity and synthesis of drimane sesquiterpenoids. Nat Prod Rep 21:449–477

    Article  CAS  PubMed  Google Scholar 

  • Komala I, Ito T, Nagashima F, Yagi Y, Asakawa Y (2010) Cytotoxic, radical scavenging and antimicrobial activities of sesquiterpenoids from the Tahitian liverwort Mastigophora diclados (Brid.) Nees (Mastigophoraceae). J Nat Med 64:417–422

    Article  CAS  PubMed  Google Scholar 

  • Kostapanos MS, Milionis HJ, Elisaf MS (2008) An overview of the extra-lipid effects of rosuvastatin. J Cardiovasc Pharmacol Ther 13:157–174

    Article  CAS  PubMed  Google Scholar 

  • Krátký M, Vinšová J, Buchta V (2012) In vitro antibacterial and antifungal activity of salicylanilide pyrazine-2-carboxylates. Med Chem 8:732–741

    Article  PubMed  Google Scholar 

  • Kuchkova KI, Aricu AN, Vlad PF (2009) Synthesis of 11-aminodrim-7-ene from drimenol. Chem Nat Compd 45:367–370

    Article  CAS  Google Scholar 

  • Kuchkova KI, Aricu AN, Vlad PF, Deleanu C, Nicolescu A (2010) Synthesis of N-containing drimane sesquiterpenoids from 11-dihomodriman-8α-ol-12-one. Chem Nat Compd 46:539–544

    Article  CAS  Google Scholar 

  • Kuchkova KI, Aricu AN, Barba AN, Vlad PF, Lipkovskii J, Simonov YS, Kravtov VK (2011) Synthesis of nitrogen-containing drimane sesquiterpenoids from 11-dihomodrim-8(9)-en-12-one. Chem Nat Compd 47:223–228

    Article  CAS  Google Scholar 

  • Kuchkova KI, Aricu AN, Barba AN, Vlad PF, Shova S, Secara E, Ungur N, Zbancioc G, Mangalagiu II (2013) An efficient and straightforward method to new organic compounds: homodrimane sesquiterpenoids with diazine units. Synlett 24:697–700

    Article  CAS  Google Scholar 

  • Lhinhatrakool T, Prabpai S, Kongsaeree P, Sutthivaiyakit S (2011) Antiplasmodial sesquiterpene alkaloids from the roots of Maytenus mekongensis. J Nat Prod 74:1386–1391

    Article  CAS  PubMed  Google Scholar 

  • Luca MC, Tura V, Mangalagiu II (2010) Considerations concerning design and mechanism of action of a new class of dual DNA intercalators. Med Hypotheses 75:627–629

    Article  CAS  PubMed  Google Scholar 

  • Mangalagiu G, Ungureanu M, Grosu G, Mangalagiu II, Petrovanu M (2001) New pyrrolopyrimidine derivatives with antifungal or antibacterial properties in vitro. Ann Pharm Fr 59:139–140

    CAS  PubMed  Google Scholar 

  • Martres P, Perfetiti P, Zahra JP, Waegell B (1993) Synthesis of norambracetal: a new ambergris derivative. Tetrahedron Lett 34:3127–3128

    Article  CAS  Google Scholar 

  • Masereel B, Pochet L, Laeckmann D (2003) An overview of inhibitors of Na(+)/H(+) exchanger. Eur J Med Chem 38:547–554

    Article  CAS  PubMed  Google Scholar 

  • Miura T, Nosaka K, Ishii H, Ishida T (2005) Antidiabetic effect of Nitobegiku, the herb Tithonia diversifolia, in KK-Ay diabetic mice. Biol Pharm Bull 28:2152–2154

    Article  CAS  PubMed  Google Scholar 

  • Owoyele VB, Wuraola CO, Soladoye AO, Olaleye SB (2004) Studies on the anti-inflammatory and analgesic properties of Tithonia diversifolia leaf extract. J Ethnopharmacol 90:317–321

    Article  PubMed  Google Scholar 

  • Racané L, Kraljević Pavelić S, Ratkaj I, Stepanić V, Pavelić K, Tralić-Kulenović V, Karminski-Zamola G (2012) Synthesis and antiproliferative evaluation of some new amidino-substituted bis-benzothiazolyl-pyridines and pyrazine. Eur J Med Chem 55:108–116

    Article  PubMed  Google Scholar 

  • Reeves DS, Phillips I, Williams JD, Wise R (1978) Disc methods of sensitivity testing and other semiquantitative methods. In: Brown D, Blowers R (eds) Laboratory methods in antimicrobial chemotherapy, part I. Churchill Livingstone, Edinburgh, pp 8–23

    Google Scholar 

  • Rüngeler P, Lyss G, Castro V, Mora G, Pahl HL, Merfort I (1998) Study of three sesquiterpene lactones from Tithonia diversifolia on their anti-inflammatory activity using the transcription factor NF-kappa B and enzymes of the arachidonic acid pathway as targets. Planta Med 64:588–593

    Article  PubMed  Google Scholar 

  • Ungureanu M, Moldoveanu C, Poeata A, Drochioiu G, Petrovanu M, Mangalagiu II (2006) New pyrimidine compounds with in vitro antimicrobial or antifungal activity. Ann Pharm Fr 64:287–288

    Article  CAS  PubMed  Google Scholar 

  • Villamizar J, Fuentes J, Salazar F, Tropper E, Alonso R (2003) Facile access to opti-cally active labdane-type diterpenes from (+)-manool: synthesis of (+)-coronarin E,(+)-15,16-epoxy-8(17),13(16),14-labdatriene, and (+)-labda-8(17),13(Z)-diene-15,16-diol. J Nat Prod 66:1623–1627

    Article  CAS  PubMed  Google Scholar 

  • Vlad PF, Ungur ND, Aricu AN, Andreeva IY (1997) Regioselective dehydration of axial and equatorial tertiary alcohols with α-methyl group in the cyclohexane ring by Swern’s reagent. Russ Chem Bull 46:800–803

    Google Scholar 

  • Wagner E, Al-Kadasi K, Zimecki M, Sawka-Dobrowolska W (2008) Synthesis and pharmacological screening of derivatives of isoxazolo[4,5-d]pyrimidine. Eur J Med Chem 43:2498–2504

    Article  CAS  PubMed  Google Scholar 

  • Zhao G, Li X, Chen W, Xi Z, Sun L (2012) Three new sesquiterpenes from Tithonia diversifolia and their anti-hyperglycemic activity. Fitoterapia 83:1590–1597

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work was supported by the Grant Romania–Moldova 418/2010 (10.820.05.19.RoF), which is highly appreciated by the authors.

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Authors and Affiliations

  1. Institute of Chemistry of the Academy of Sciences of Moldova, Academy 3, MD-2028, Chişinău, Republic of Moldova

    Kaleria Kuchkova, Aculina Aricu, Elena Secara, Alic Barba, Pavel Vlad & Nicon Ungur

  2. “Grigore T. Popa” University of Medicine and Pharmacy of Iasi, Str. Universitatii 16, 700115, Iasi, Romania

    Cristina Tuchilus

  3. “P. Poni” Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda 41-A, 700487, Iasi, Romania

    Sergiu Shova

  4. Organic Chemistry Department, “Al. I. Cuza” University of Iasi, Bd. Carol 11, 700506, Iasi, Romania

    Gheorghita Zbancioc & Ionel I. Mangalagiu

  5. Department of Organic and Biochemistry, “Al. I. Cuza” University of Iasi, 11 Carol I, 700506, Iasi, Romania

    Ionel I. Mangalagiu

Authors
  1. Kaleria Kuchkova
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  2. Aculina Aricu
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  3. Elena Secara
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  4. Alic Barba
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  5. Pavel Vlad
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  6. Nicon Ungur
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  7. Cristina Tuchilus
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  8. Sergiu Shova
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  9. Gheorghita Zbancioc
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  10. Ionel I. Mangalagiu
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Corresponding author

Correspondence to Ionel I. Mangalagiu.

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Kuchkova, K., Aricu, A., Secara, E. et al. Design, synthesis, and antimicrobial activity of some novel homodrimane sesquiterpenoids with diazine skeleton. Med Chem Res 23, 1559–1568 (2014). https://doi.org/10.1007/s00044-013-0720-3

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  • DOI: https://doi.org/10.1007/s00044-013-0720-3

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