Figure 1. General structure of N-phenyl and N-phenylalkylmaleimides.

Figure 2. Opening of maleimide to maleamic acid under basic conditions.

Scheme 1. 

Figure 3. Time-to-kill curves of maleimides 7–11 at 1 × MFC against C. albicans ATCC 10231.

Figure 4. Microtiter plate showing MIC values in μg/mL (white line) of N-phenylmaleimide 7 without pre-incubation (0 days) and with different times (1–7 days) of pre-incubation into the growth media, against Candida albicans ATCC 10231 using the CLSI (formerly NCCLS) M27 A2 method.

Figure 5. (a–e) UV spectra of each maleimide and its respective maleamic acid in recently prepared water solutions. In detail: (a) N-phenylamaleimide 7 and N-phenylmaleamic acid 2. (b) N-bencylmaleimide 8 and N-bencylmaleamic acid 3. (c) N-phenethylmaleimide 9 and N-phenethylmaleamic acid 4. (d) N-phenylpropylmaleimide 10 and N-phenylpropylmaleamic acid 5. (e) N-phenylbutylmaleimide 11 and N-phenylbutylmaleamic acid 6. (a′–e′) UV spectra of each maleimide (250 μg/mL) 7–11 in aqueous solutions, after different times of incubation (0 to 72 h).

Minimum inhibitory concentration (MIC) and Minimum fungicidal concentration (MFC) values (μg/mL) of N-phenyl- and N-phenylalkyl-maleamic acids and maleimides acting against Candida spp.

Full-size image (5K)

ATCC, American Type Culture Collection (Rockville, MD, USA); C, Centro de Referencia en Micología (CEREMIC, Rosario, Argentina); Amp B, amphotericin B; Ket, ketoconazole.

MIC values (μg/mL) against Candida albicans ATCC 10231 of maleimides 7–11, without pre-incubation (0 days) and with different times (1–7 days) of pre-incubation at 37 °C in the growth media, using the CLSI (formerly NCCLS) M27 A2 method

T.P., Time of pre-incubation of maleimides in the growth media.

Fractional Inhibitory Concentration Indexes (FICI) of maleimides 7–11 in combination with maleamic acids 2–6 against Candida albicans ATCC 10231

MIC values (μg/mL) of combinations of maleimides 7–11 (100% → 0%) with maleamic acids 2–6 (0% → 100%)