Synthesis of New Hybrid Derivatives from Metronidazole and Eugenol Analogues as Trypanocidal Agents

Authors

  • Mônica Fraccarolli Pelozo Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Brazil
  • Giovanna Fiori Serpa Lima Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Brazil
  • Cleydson Finotti Cordeiro Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Brazil
  • Luana Sueli Silva Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Brazil
  • Ivo Santana Caldas UNIFAL-MG
  • Diogo Teixeira Carvalho Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Brazil https://orcid.org/0000-0002-6362-2822
  • Stefânia Neiva Lavorato Centro de Ciências Biológicas e Saúde, Universidade Federal do Oeste da Bahia,Brazil
  • Jamie Anthony Hawkes Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Brazil https://orcid.org/0000-0003-3343-1854
  • Lucas Lopardi Franco Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Brazil https://orcid.org/0000-0002-5196-9845

DOI:

https://doi.org/10.18433/jpps31839

Abstract

Background: The search for new drug compounds is always challenging and there are several different strategies that involve the most varied and creative approaches in medicinal chemistry. One of them is the technique of molecular hybridisation: forming a hybrid compound from two or more pharmacophoric subunits. These hybrids may maintain the characteristics of the original compound and preferably show improvements to its pharmacological action, with reduced side effects and lower toxicity when compared to the original components. This study specifically focuses on synthesising hybrid molecules which demonstrate trypanocidal activity against the epimastigote and trypomastigote forms of Trypanosoma cruzi. Methods: In this context, this study centres on the synthesis of a novel structural scaffold via molecular hybridisation; by using a triazole species to link a metronidazole unit to a eugenol analogue unit, the objective being to combine their therapeutic properties into a new molecular structure. The resulting hybrid molecules were evaluated against T. cruzi which is responsible for high incidences of trypanosomiasis in tropical countries such as Brazil. Results: The results of this study showed an improvement in the anti-parasitic activity of the hybrid compounds with the best result coming from hybrid compounds [8] and [9], which present an activity similar to the control drug benznidazole. The new compounds, utilising a triazole species as a coupling connector, demonstrated promising results and has highlighted the path for planning similar structural patterns to investigate new compounds. Conclusions: In summary, we can conclude that the synthesised hybrid compounds demonstrate that using a triazole to link metronidazole with natural phenols, produces hybrid molecules that are promising as a new class of compounds of therapeutic interest for further investigation.

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Published

2021-08-16

How to Cite

Pelozo , M. F., Lima , G. F. S., Cordeiro , C. F., Silva, L. S., Caldas , I. S., Carvalho , D. T., Lavorato , S. N., Hawkes, J. A., & Franco , L. L. (2021). Synthesis of New Hybrid Derivatives from Metronidazole and Eugenol Analogues as Trypanocidal Agents. Journal of Pharmacy & Pharmaceutical Sciences, 24, 421–434. https://doi.org/10.18433/jpps31839

Issue

Section

Pharmaceutical Sciences; Original Research Articles