Antiparasitic activity of synthetic curcumin monocarbonyl analogues against Trichomonas vaginalis

• Published in: Biomedicine & pharmacotherapy Vol. 111; pp. 367 - 377
• Main Authors: Carapina da Silva, Caroline, Pacheco, Bruna Silveira, das Neves, Raquel Nascimento, Dié Alves, Mirna Samara, Sena-Lopes, Ângela, Moura, Sidnei, Borsuk, Sibele, de Pereira, Claudio Martin Pereira
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.03.2019; Elsevier
• Subjects: Antiparasitic; Arylideneketones; C5-curcuminoids; Dibenzylideneacetone; Metronidazole; Antiparasitic; Dibenzylideneacetone; Metronidazole; Arylideneketones; C5-curcuminoids
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.12.058

[Display omitted] •Curcumin monocarbonyl analogues were synthesized in good yields by easy protocols.•Three analogues inhibited Trichomonas vaginalis growth similarly to metronidazole.•Curcumin analogues eradicated T. vaginalis growth within 24 hrs.•Analogue 3e did not induce any level of cytotoxicity on VERO cells.•The analogues reported are worth exploring as potential anti-T. vaginalis agents. Trichomoniasis is a parasitic infection caused by Trichomonas vaginalis and it is considered to be the most common non-viral sexually transmitted infection in the world. Since the 1960s, nitroimidazoles such as metronidazole are the drugs of choice for the treatment of trichomoniasis, but many adverse effects and allergic reactions may result from their use. Reports of metronidazole-resistant infections also highlight the importance for the search of new anti-T. vaginalis agents. Considering this, herein we report the anti-T. vaginalis evaluation of 21 synthetic monocarbonyl analogues of curcumin, which itself has been reported to possess antiparasitic potential. From the in vitro analysis of the synthetic molecules, untreated trophozoites, and metronidazole at 100 μM, it was observed that three curcumin analogues (3a, 3e, and 5e) exhibited anti-T. vaginalis activity comparable to metronidazole (no significant statistical difference). Optimal antiparasitic concentrations were determined to be 80 μM and 90 μM for propanone derivatives 3a and 3e, respectively, and 200 μM for cyclohexanone derivative 5e. Kinetic growth curves showed that, after 24 h, the trophozoites were completely inhibited. At the tested concentrations, natural curcumin did not significantly inhibit the growth of trophozoites, therefore demonstrating that the designed synthetic molecules not only have better chemical stability, but also higher anti-T. vaginalis potential. Cytotoxicity analysis, performed on VERO cells, demonstrated low, moderate and high cytotoxic effects for analogues 3e, 5e and 3a, respectively. This study suggests that these analogues possess chemical features of interest to be further explored as alternatives for the treatment of trichomoniasis.