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. 2015 May 12;20(5):8499-520.
doi: 10.3390/molecules20058499.

Microwave-Assisted Synthesis of Novel Pyrazolo[3,4-g][1,8]naphthyridin-5-amine with Potential Antifungal and Antitumor Activity

Paola Acosta  1 , Estefanía Butassi  2 , Braulio Insuasty  3 , Alejandro Ortiz  4 , Rodrigo Abonia  5 , Susana A Zacchino  6 , Jairo Quiroga  7
Affiliations

Microwave-Assisted Synthesis of Novel Pyrazolo[3,4-g][1,8]naphthyridin-5-amine with Potential Antifungal and Antitumor Activity

Paola Acosta et al. Molecules. .

Abstract

The microwave assisted reaction between heterocyclic o-aminonitriles 1 and cyclic ketones 2 catalyzed by zinc chloride led to new series of pyrazolo[3,4-b] [1,8]naphthyridin-5-amines 3 in good yields. This procedure provides several advantages such as being environmentally friendly, high yields, simple work-up procedure, broad scope of applicability and the protocol provides an alternative for the synthesis of pyrazolonaphthyridines. The whole series showed antifungal activities against Candida albicans and Cryptococcus neoformans standardized strains, being compounds with a 4-p-tolyl substituent of the naphthyridin scheleton (3a, 3d and 3g), the most active ones mainly against C. albicans, which appear to be related to their comparative hydrophobicity. Among them, 3d, containing a cyclohexyl fused ring, showed the best activity. The anti-Candida activity was corroborated by testing the three most active compounds against clinical isolates of albicans and non-albicans Candida strains. These compounds were also screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines. Compounds 3a and 3e showed remarkable antitumor activity against cancer cell lines, with the most important GI50 values ranging from 0.62 to 2.18 μM.

Keywords: Candida albicans; Cryptococcus neoformans; antifungal activity; antitumoral activity; microwave irradiation; pyrazolonaphthyridines.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Synthesis of pyrazolo[3,4-b][1,8]naphthyridin-5-amine 3.
Scheme 2
Scheme 2
Proposed mechanism.
Figure 1
Figure 1
Comparative curves of the growth inhibition of C. albicans ATCC 10231 produced by compounds 3a, 3d and 3g at different concentrations. Inhibition percentages are the means ± SD obtained from experiments in triplicate.
Figure 2
Figure 2
LogP vs. inhibition percentage of C. albicans growth, by 3a–i at 125 µg∙mL−1.
See this image and copyright information in PMC

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