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Synthesis and Evaluation of Biological Activity of Homodrimane Sesquiterpenoids Bearing Hydrazinecarbothioamide or 1,2,4-Triazole Unit

Synthesis of novel (+)-sclareolide-based homodrimane sesquiterpenoids bearing hydrazinecarbothioamide or N-substituted 1,2,4-triazole unit has been reported. These heterocyclic compounds demonstrate promising in vitro antifungal and antibacterial activities toward fungal species Aspergillus niger, Fusarium solani, Penicillium chrysogenum, Penicillium frequentans, and Alternaria alternata and bacteria strains Bacillus sp. and Pseudomonas aeruginosa at minimum inhibitory concentration level of μg/ml. In addition, two homodrimane sesquiterpenoids with hydrazinecarbothioamide fragment show cytotoxicity toward human ovarian carcinoma cells A2780 and A2780cis with half maximal inhibitory concentration values in range of 9–15 μM.

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  1. Jansen, B. J. M.; de Groot, Ae. Nat. Prod. Rep. 2004, 21, 449.

  2. (a) Kubo, I. In Studies in Natural Products Chemistry; Atta-ur-Rahman, Ed.; Elsevier: Amsterdam, 1995, Vol. 17, p. 233. (b) Taniguchi, M.; Yano, Y.; Motoba, K.; Tanaka, T.; Oi, S.; Haraguchi, H.; Hashimoto, K.; Kubo, I. Agric. Biol. Chem. 1988, 52, 1881.

  3. Fritz, G. L.; Mills, G. D., Jr.; Warthen, J. D., Jr.; Waters, R. M. J. Chem. Ecol. 1989, 15, 2607.

    Article  CAS  PubMed  Google Scholar 

  4. Barrero, A. F.; Manzaneda, E. A.; Altarejos, J.; Salido, S.; Ramos, J. M.; Simmonds, M. S. J.; Blaney, W. M. Tetrahedron 1995, 51, 7435.

    Article  CAS  Google Scholar 

  5. Ciocarlan, A.; Aricu, A.; Lungu, L.; Edu, C.; Barba, A.; Shova, S.; Mangalagiu, I. I.; D'Ambrosio, M.; Nicolescu, A.; Deleanu, C.; Vornicu, N. Synlett 2017, 565.

  6. Viegas, C., Jr.; Danuello, A.; da Silva Bolzani, V.; Barreiro, E. J.; Fraga, C. A. M. Curr. Med. Chem. 2007, 14, 1829.

    Article  Google Scholar 

  7. Kuchkova, K.; Aricu, A.; Barba, A.; Vlad, P.; Shova, S.; Secara, E.; Ungur, N.; Zbancioc, Gh.; Mangalagiu, I. I. Synlett 2013, 697.

  8. Kuchkova, K.; Aricu, A.; Secara, E.; Barba, A.; Vlad, P.; Ungur, N.; Tuchilus, C.; Shova, S.; Zbancioc, Gh.; Mangalagiu, I. I. Med. Chem. Res. 2014, 23, 1559.

    Article  CAS  Google Scholar 

  9. (a) Kharb, R.; Sharma, P. C.; Yar, M. S. J. Enzyme Inhib. Med. Chem. 2011, 26, 1. (b) Gupta, D.; Jain, D. K. J. Adv. Pharm. Technol. Res. 2015, 6, 141. (c) Shen, Q.-K.; Liu, C.-F.; Zhang, H.-J.; Tian, Y.-S.; Quan, Z.-S. Bioorg. Med. Chem. Lett. 2017, 27, 4871. (d) Silva-Ortiz, A. V.; Bratoeff, E.; Ramírez-Apan, T.; Heuze, Y.; Sánchez, A.; Soriano, J.; Cabeza, M. Bioorg. Med. Chem. 2015, 23, 7535.

  10. Kuchkova, K. I.; Aricu, A. N.; Sekara, E. S.; Barba, A. N.; Vlad, P. F.; Makaev, F. Z.; Melnic, E.; Kravtsov, V. Kh. Chem. Nat. Compd. 2015, 51, 684. [Khim. Prir. Soedin. 2015, 589.]

  11. Cucicova, C.; Rudic, V.; Aricu, A.; Cepoi, L.; Rudi, L.; Secara, E.; Valuta, A.; Barba, A.; Miscu, V.; Vlad, P.; Chiriac, T. MD Patent 4327.

  12. Styngach, E. P.; Malinovskii, S. T.; Bets, L. P.; Vlad, L. A.; Gdanets, M.; Makaev, F. Z. J. Struct. Chem. 2005, 46, 765. [Zh. Struktur. Khim. 2005, 46, 785.]

  13. Namratha, B.; Gaonkar, S. L. Int. J. Pharm. Pharm. Sci. 2014, 6, 73.

    CAS  Google Scholar 

  14. Macaev, F.; Rusu, G.; Pogrebnoi, S.; Gudima, A.; Stingaci, E.; Vlad, L.; Shvets, N.; Kandemirli, F.; Dimoglo, A.; Reynolds, R. Bioorg. Med. Chem. 2005, 13, 4842.

    Article  CAS  PubMed  Google Scholar 

  15. Jogdand, G. F. Ph. D. Thesis, University of Pune: Pune, 2016.

  16. (a) Antimicrobial Susceptibility Testing (AST) Standards M07 and M100; National Committee on Clinical Laboratory Standards (NCCLS), 2003. (b) Cavalieri, S. J.; Harbeck, R. J.; McCarter, Y. S.; Ortez, J. H.; Rankin, I. D.; Sautter, R. L.; Sharp, S. E.; Spiegel, C. A. Manual of Antimicrobial Susceptibility Testing; Coyle, M. B., Ed.; American Society for Microbiology: Washington, 2005. (c) Arendrup, M. C.; Verweij, P.; Nielsen, H. V. Antimicrob. Agents Chemother. 2017, 61, e01659-16. (d) Thompson, G. R., III; Fothergill, A. W.; Wiederhold, N. P.; Vallor, A. C.; Wickes, B. L.; Patterson, T. F. Antimicrob. Agents Chemother. 2008, 52, 2959. (e) Espinel-Ingroff, A.; Rezusta, A. J. Clin. Microbiol. 2002, 40, 2101.

  17. CrysAlis RED, v1.171.34.76; Oxford Diffraction Ltd.: Abingdon, 2003.

  18. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. J. Appl. Crystallogr. 2009, 42, 339.

    Article  CAS  Google Scholar 

  19. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, A64, 112.

  20. Sîrbu, A.; Palamarciuc, O.; Babak, M. V.; Lim, J. M.; Ohui, K.; Enyedy, E. A.; Shova, S.; Darvasiová, D.; Rapta, P.; Ang, W. H.; Arion, V. B. Dalton Trans. 2017, 46, 3833.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Michele D’Ambrosio.

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Supplementary information file containing 1H and 13C NMR spectra of compounds 6, 7ad, 8ad, and 9ad, HRMS of compounds 7c and 8d, and single crystal X-ray crystallographic data of compounds 8c and 9d is available at the journal website

Published in Khimiya Geterotsiklicheskikh Soedinenii, 2019, 55(8), 716–724

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Lungu, L., Ciocarlan, A., Barba, A. et al. Synthesis and Evaluation of Biological Activity of Homodrimane Sesquiterpenoids Bearing Hydrazinecarbothioamide or 1,2,4-Triazole Unit. Chem Heterocycl Comp 55, 716–724 (2019).

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  • homodrimane sesquiterpenoid
  • hydrazinecarbothioamide
  • 1,2,4-triazole
  • antibacterial activity
  • anticancer activity
  • antifungal activity
  • microwave irradiation