Novel pyrazine analogs of chalcones: synthesis and evaluation of their antifungal and antimycobacterial activity.

Marta Kucerova-Chlupacova,Vladimir Buchta,Marcela Vejsova,Jiri Kunes,Veronika Opletalova

doi:10.3390/molecules20011104

Marta Kucerova-Chlupacova, Vladimir Buchta + Show 3 more

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https://doi.org/10.3390/molecules20011104

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Abstract

Infectious diseases, such as tuberculosis and invasive mycoses, represent serious health problems. As a part of our long-term efforts to find new agents for the treatment of these diseases, a new series of pyrazine analogs of chalcones bearing an isopropyl group in position 5 of the pyrazine ring was prepared. The structures of the compounds were corroborated by IR and NMR spectroscopy and their purity confirmed by elemental analysis. The susceptibility of eight fungal strains to the studied compounds was tested. The results have been compared with the activity of some previously reported propyl derivatives. The only strain that was susceptible to the studied compounds was Trichophyton mentagrophytes. It was found that replacing a non-branched propyl with a branched isopropyl did not have a decisive and unequivocal influence on the in vitro antifungal activity against T. mentagrophytes. In vitro activity against Trichophyton mentagrophytes comparable with that of fluconazole was exhibited by nitro-substituted derivatives. Unfortunately, no compound exhibited efficacy comparable with that of terbinafine, which is the most widely used agent for treating mycoses caused by dermatophytes. Some of the prepared compounds were assayed for antimycobacterial activity against M. tuberculosis H37Rv. The highest potency was also displayed by nitro-substituted compounds. The results of the present study are in a good agreement with our previous findings and confirm the positive influence of electron-withdrawing groups on the B-ring of chalcones on the antifungal and antimycobacterial activity of these compounds.

Highlights

Infectious diseases used to be, and in some regions of the world still are, the major cause of death.Tuberculosis remains a severe global public health threat, especially in the context of the emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains in all countries of the world [1,2,3,4,5,6]
It can only be concluded that replacing a non-branched propyl with a branched isopropyl does not have a decisive and unequivocal influence on the in vitro antifungal activity against
Potency of (E)-1-(5-isopropylpyrazin-2-yl)-3-(2-nitrophenyl)-prop-2-en-1-one (4g), and (E)-1-(5-isopropyl-pyrazin-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one (4i) was comparable to that of fluconazole, which is sometimes used for the treatment of mycoses caused by Trichophyton spp. [42,43], but lower than that of voriconazole and terbinafine

Summary

Introduction

Infectious diseases used to be, and in some regions of the world still are, the major cause of death.Tuberculosis remains a severe global public health threat, especially in the context of the emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains in all countries of the world [1,2,3,4,5,6]. It can only be concluded that replacing a non-branched propyl with a branched isopropyl does not have a decisive and unequivocal influence on the in vitro antifungal activity against. Potency of (E)-1-(5-isopropylpyrazin-2-yl)-3-(2-nitrophenyl)-prop-2-en-1-one (4g), and (E)-1-(5-isopropyl-pyrazin-2-yl)-3-(4-nitrophenyl)prop-2-en-1-one (4i) was comparable to that of fluconazole, which is sometimes used for the treatment of mycoses caused by Trichophyton spp. Terbinafine is most widely used agent to treat mycoses caused by dermatophytes and other fungi [42,44]. Voriconazole belongs to the highly effective systemic antifungal drugs with a favourable risk-benefit ratio, and with distinct in vitro activity against dermatophytes, yeasts and some molds [45] but clinically it is used to treat invasive aspergillosis [46,47]

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