Skip to main content
SpringerLink
Log in

Synthesis, thermal behavior and biological evaluation of benzodioxole derivatives as potential cytotoxic and antiparasitic agents

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Benzodioxole derivatives are known to possess a broad spectrum of activities such. In addition to the synthetic derivatives, natural products that have the benzodioxole subunit, such as piperine, have shown potential anti-tumor activity through induction of apoptosis and antiparasitic activity. Thus, compounds containing the benzodioxole subunit have a broad spectrum of activity and raise expectations in therapeutic innovation. Through the analysis of the compounds by conventional spectroscopic methods (1H NMR and 13C NMR), it was possible to observe that all of them fulfilled the prerequisites for the structural characterizations. The information being corroborated through the characterization by pyrolysis coupled to the mass spectrometer, since all the compounds presented characteristic fragments with the respective masses. In addition to having performed the thermal analysis of the NW-11 derivative by means of TG, DSC and obtaining the degradation kinetics of the derivative. As for the antiproliferative activity, it was possible to conclude that among all benzoindoxole derivatives tested, NW-03 can be pointed out as promising in the study for antitumor activity. While for the results of the antiparasitic activity, it was possible to choose the derivatives NW-02 and NW-09 as potential trypanocidal. For activity against Leishmania, the compound NW-14 presented itself as the promising compound, in addition to the compounds NW-2 and NW-15, indicating the importance of the aromatic nucleus unsubstituted in thiosemicarbazones in the increase of the antiparasitic activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. Romeiro LAS, Ferreira MS, Silva LL, Castro HC, Miranda ALP, Silva CLM et al. Discovery of LASSBio-772, a 1,3-benzodioxole N-phenylpiperazine derivative with potent alpha 1A/D-Adrenergic receptor blocking properties. Eur J Med Chem. 2011;46:3000–12.

    Article  CAS  PubMed  Google Scholar 

  2. Fraga AMC, Barreiro JE. A utilização do safrol, principal componente químico do óleo de sassafráz, na síntese de substancias bioativas na cascata do ácido aracdônico: anti-inflamatórios, analgésicos e anti-trombóticos. Química Nova. 1998;5:744–59.

    Google Scholar 

  3. Maia RC, Silva LL, Mazzeu EF, Fumian MM, Rezende CM, Doriguetto AC et al. Synthesis and analgesic profile of conformationally constrained N-acylhydrazone analogues: Discovery of novel N-arylideneamino quinazolin-4(3H)-one compounds derived from natural safrole. Bioorg Med Chem. 2009;17:6517–25.

    Article  CAS  PubMed  Google Scholar 

  4. Yaffe PB, Doucette CD, Walsh M, Hoskin DW. Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells. Exp Mol Pathol. 2013;94:109–14.

    Article  CAS  PubMed  Google Scholar 

  5. Fernandes A, Almeida L, Ferreira PE, Marques MJ, Rocha RP, Coelho LFL et al. Synthesis and biological evaluation of novel piperidine-benzodioxole derivatives designed as potential leishmanicidal drug candidates. Bioorg Med Chem. 2015;15:3346–9.

    Article  Google Scholar 

  6. Abbas SY, Al-Harbi RAK, El-Sharief MAMS. Synthesis and anticancer activity of thiourea derivatives bearing a benzodioxole moiety with EGFR inhibitory activity, apoptosis assay and molecular docking study. Eur J Med Chem. 2020;198:112363.

    Article  CAS  PubMed  Google Scholar 

  7. Gupta SD, Rao GB, Bommaka MK, Raghavendra NM, Aleti S. Eco-sustainable synthesis and biological evaluation of 2-phenyl 1,3-benzodioxole derivatives as anticancer, DNA binding and antibacterial agents. Arab J Chem. 2016;9:1875–83.

    Article  Google Scholar 

  8. Gupta SD, Rao GB, Bommaka MK, Raghavendra NM, Aleti S. Eco-sustainable synthesis and biological evaluation of 2-phenyl 1,3-benzodioxole derivatives as anticancer, DNA binding and antibacterial agentes. Am J Chem. 2016;9:S1875–83.

    Google Scholar 

  9. Degirmencioglu I, Tuncay FO, Cakmak U, Kolcuoglu Y. The synthesis of novel piperazine-benzodioxole substituted phthalocyanines and investigation of their α-amylase and tyrosinase inhibition properties. J Organomet Chem. 2021;951:122012.

    Article  CAS  Google Scholar 

  10. Wang HH, Qiu KM, Cui HE, Yang YS, Luo Y, Xing M et al. Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives containing benzodioxole as potential anticancer agents. Bioorg Med Chem. 2013;21:448–55.

    Article  CAS  PubMed  Google Scholar 

  11. Silva LMMG, Oliveira JF, Silva WL, Silva AL, Almeida Junior ASA, Santos VHB et al. New 1, 3-benzodioxole derivatives: Synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis. Chem-Biol Interact. 2018;283:20–29.

    Article  PubMed  Google Scholar 

  12. Espíndola JW, Cardoso MV, Filho GB, Oliveira E, Silva DA, Moreira DR et al. Sales Junior PA, Romanha AJ, Leite AC. Synthesis and structure–activity relationship study of a new series of antiparasitic aryloxyl thiosemicarbazones inhibiting Trypanosoma cruzi cruzain. Eur J Med Chem. 2015;101:28.

    Article  Google Scholar 

  13. Santiago EF, Oliveira SA, Oliveira Filho GB, Moreira DRM, Gomes PAT, Silva AL et al. Evaluation of the Anti-Schistosoma mansoni activity of thiosemicarbazones and thiazoles. Antimicrobial Agents Chemother 2014;58:352–63.

    Article  Google Scholar 

  14. Macêdo RO, Nascimento TG. Quality control of thiabendazole pre-formulation and tablets by TG and DSC coupled to the photovisual system. Thermochim Acta. 2002;392–393:85–92.

    Article  Google Scholar 

  15. Monks A, Scudiero D, Skehan P, Shomaker R, Paull K, Vistica D et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst. 1991;83:657–61.

    Article  Google Scholar 

  16. Tita B, Fulias A, Bandur G, Marian E, Tita D. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms. J Pharm Biomed Anal. 2011;56:221–7.

    Article  CAS  PubMed  Google Scholar 

  17. Franklim TN, Freire-de-Lima L, chaves OA, LaRocque-de-Freitas IF, Silva-Trindade JD, Netto-Ferreira JC et al. Design, Synthesis, Trypanocidal Activity, and Studies on Human Albumin Interaction of Novel S-Alkyl-1,2,4-triazoles J. Braz Chem Soc. 2019;30:1378–94.

    Google Scholar 

  18. Singh P, Kumari K, Dubey M, Vishvakarma VK, Mehrotrac GK, Pandey ND et al. Ionic liquid catalyzed synthesis of 7-phenyl-1,4,6,7- tetrahydro-thiazolo [5,4-d]pyrimidine-2,5-diones. Comptes Rendus Chim. 2012;15:504–10.

    Article  CAS  Google Scholar 

  19. Nikalje A, Shaikh A, Shaikh S, Khan F, Sangshetti J, Shinde D. Microwave assisted synthesis and docking study of N-(2-oxo-2-(4-oxo-2-substituted thiazolidin-3ylamino)ethyl)benzamide derivatives as anticonvulsant agents. Bioorg Med Chem Lett. 2014;24:5558–62.

    Article  CAS  PubMed  Google Scholar 

  20. Lafayette EA, Almeida SMV, Pitta MGR, Beltrão EIC, Silva TG, Moura RO et al. Synthesis, DNA binding and topoisomerase I inhibition activity of thiazacridine and imidazacridine derivatives. Molecules. 2013;18:15035–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Moreira TLB, Barbosa AFS, Veiga-Santos P, Henriques C, Henriques-Pons A, Galdino SL et al. Effect of thiazolidine LPSF SF29 on the growth and morphology of Trypanosoma cruzi. Int J Antimicrob Agents. 2013;41:183–7.

    Article  Google Scholar 

  22. Santiago EDF, Oliveira SA, Oliveira Filho GB, Moreira DRM, Gomes PAT, Silva AL et al. Evaluation of the Anti-Schistosoma mansoni Activity of Thiosemicarbazones and Thiazoles. Antimicrob Agents Chemother 2014;58:352–63.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Federal University of Pernambuco, Laboratório de Química e Inovação Terapêutica, Recife, PE, Brazil

    Willams Leal Silva, Cezar Augusto da Cruz Amorim, Pedro Henrique do Bomfim Nascimento & Maria do Carmo Alves de Lima

  2. Federal University of Paraíba, Unified Laboratories of Pharmaceutical Development and Assays, Department of Pharmaceutical Sciences, João Pessoa, PB, 58059-970, Brazil

    Fabricio Havy Dantas de Andrade, Taynara Batista Lins & Fábio Santos de Souza

  3. Federal University of the São Francisco Valley (UNIVASF), Department of Medicine, Paulo Afonso, BA, 48607-190, Brazil

    Anekécia Lauro da Silva

  4. Federal University of Pernambuco, Laboratório de Tecnologia dos Medicamentos, Recife, PE, Brazil

    Maria Joanellys dos Santos Lima, Paulo César Dantas da Silva, Williana Tôrres Vilela & Rosali Maria Ferreira da Silva

  5. University for the International Integration of Afro-Brazilian Lusophony (UNILAB), Redenção, CE, 62790-970, Brazil

    Jamerson Ferreira de Oliveira

Authors
  1. Willams Leal Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fabricio Havy Dantas de Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taynara Batista Lins
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anekécia Lauro da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cezar Augusto da Cruz Amorim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Joanellys dos Santos Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paulo César Dantas da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Williana Tôrres Vilela
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pedro Henrique do Bomfim Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jamerson Ferreira de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Fábio Santos de Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Maria do Carmo Alves de Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Rosali Maria Ferreira da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Joanellys dos Santos Lima.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Silva, W.L., de Andrade, F.H.D., Lins, T.B. et al. Synthesis, thermal behavior and biological evaluation of benzodioxole derivatives as potential cytotoxic and antiparasitic agents. Med Chem Res 32, 944–956 (2023). https://doi.org/10.1007/s00044-023-03047-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-023-03047-5

Keywords

Search

Navigation