Antifungal activity of aminoalcohols and diamines against dermatophytes and yeast

Article abstract of DOI:10.1007/s00044-020-02636-y

Dermatomycoses are infections caused by fungi and yeasts and the drug treatment is considered expensive and extensive. Researchers are synthesizing new organic compounds in order to obtain more effective molecules that provide reduced adverse effects. Our research group has synthesized and evaluated the biological activities of aminoalcohol and diamine derivatives, which were considered active against human pathogenic fungi. Therefore, the objective of this study was to evaluate the in vitro antifungal activity of aminoalcohols and diamine derivatives against fungi and yeasts that cause dermatomycoses. The minimum inhibitory concentrations (MICs) and the minimum fungicidal concentration (MFC) of aminoalcohol (1–4) and diamine (5–13) derivatives was determined against Trichophyton mentagrophytes, T. rubrum, Epidermophyton floccosum, and Candida albicans according to protocols from the Clinical and Laboratory Standards Institute. All molecules exhibited fungicidal activity against the evaluated fungal strains, with the MIC and MFC ranging between 0.12 and 1000 μg/mL for filamentous fungi and 0.6 and 1250 μg/mL for yeasts. The best activity was attributed to diamines compared to aminoalcohols, with an emphasis on molecules 6 and 7. These results demonstrate the antifungal potential of the evaluated aminoalcohols and diamines against the four primary fungal species that cause dermatomycoses. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s00044-020-02636-y

MEDICINAL
CHEMISTRY
RESEARCH
Medicinal Chemistry Research
https://doi.org/10.1007/s00044-020-02636-y
ORIGINAL RESEARCH
Antifungal activity of aminoalcohols and diamines against
dermatophytes and yeast
1
Bruno A. de Oliveira2 Angelina M. de Almeida2 Renata P. do Carmo1
● ●
●
●
●
●
César A. Caneschi
Francislene J. Martins1 Mauro V. de Almeida2 Nádia R. B. Raposo1
Received: 4 June 2020 / Accepted: 12 September 2020
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Dermatomycoses are infections caused by fungi and yeasts and the drug treatment is considered expensive and extensive.
Researchers are synthesizing new organic compounds in order to obtain more effective molecules that provide reduced
adverse effects. Our research group has synthesized and evaluated the biological activities of aminoalcohol and diamine
derivatives, which were considered active against human pathogenic fungi. Therefore, the objective of this study was to
evaluate the in vitro antifungal activity of aminoalcohols and diamine derivatives against fungi and yeasts that cause
dermatomycoses. The minimum inhibitory concentrations (MICs) and the minimum fungicidal concentration (MFC) of
aminoalcohol (1–4) and diamine (5–13) derivatives was determined against Trichophyton mentagrophytes, T. rubrum,
Epidermophyton floccosum, and Candida albicans according to protocols from the Clinical and Laboratory Standards
Institute. All molecules exhibited fungicidal activity against the evaluated fungal strains, with the MIC and MFC ranging
between 0.12 and 1000 μg/mL for filamentous fungi and 0.6 and 1250 μg/mL for yeasts. The best activity was attributed to
diamines compared to aminoalcohols, with an emphasis on molecules 6 and 7. These results demonstrate the antifungal
potential of the evaluated aminoalcohols and diamines against the four primary fungal species that cause dermatomycoses.
Graphical Abstract
●
●
●
Keywords Aminoalcohols Diamines Antifungal activity Dermatomycoses
* César A. Caneschi
2
Departamento de Química, Instituto de Ciências Exatas,
Universidade Federal de Juiz de Fora, Rua José Lourenço Kelmer,
s/n, Juiz de Fora, MG 36036-330, Brazil
Cacaneschi@yahoo.com.br
1
Núcleo de Pesquisa e Inovação em Ciências da Saúde (NUPICS),
Faculdade de Farmácia, Universidade Federal de Juiz de Fora, Rua
José Lourenço Kelmer, s/n, Juiz de Fora, MG 36036-330, Brazil

Medicinal Chemistry Research
Introduction
the minimum inhibitory concentration (MIC) and minimum
fungicidal concentration (MFC) values ranging between
0.12 and 1000 μg/mL for filamentous fungi and 0.6 and
1250 μg/mL for yeasts (Table 1), which corroborates data
from the literature attributing the antimicrobial action to
these classes of compounds [15, 17, 19, 25]. The lowest
MIC and MFC values were provided by diamine 6, whose
antifungal action could be attributed to its amphiphilic
property, since it favors its interaction with the cells, as
described in previous studies [21–23, 26, 27]. Among the
molecules evaluated, diamine 6 with a lateral aliphatic chain
bearing 12 carbon atoms exhibited better antifungal action
against the tested microbial strains, with the MIC value in
the range of 0.12–4.8 μg/mL.
Diamine 6 also presented the lowest MIC value (0.12 μg/
mL) against T. rubrum CCT 5507 URM 1666 strain and
this MIC value was less than the value obtained with the
reference drugs (terbinafine, ketoconazole, itraconazole, and
amorolfine). This result deserves attention since Lima et al.
[28] have considered this specie as the main responsible for
dermatomycoses in humans. In addition, the existence of
antifungals-resistant clinical isolates of this species is
common, which may be related to the presence of trans-
porters associated with cellular efflux identified as
TruMDR1 and TruMDR2 [29].
As shown in Table 1, the diamines 5–13 exhibited the
best activity (MICs: 0.97–3.9 μg/mL) compared with the
aminoalcohols 1–4 (MICs: 0.462–500 μg/mL). There was a
reduction in the antifungal activity of the diamines with the
increase in the number of carbon atoms present in the
spacers between the functional groups. The presence of
two- and four-carbon spacers provided MICs of 0.24–15.62
and 0.6–312 μg/mL, respectively. These results suggest a
decrease in the biological response due to the increased
lipophilicity (longer than 12 carbon atoms in the lateral
alkyl chain). Krauss et al. [30] evaluated the antimicrobial
activity of N-alkyl-trans-decahydroisoquinoline molecules
and observed that the biological action was related to the
length of the alkyl chain, with the best activity being
attributed to the presence of chains composed of 10–12
carbon atoms. Tang et al. [31] evaluated the antifungal
potential of quinazolinones, quinoxalines, and benzopyrans
and found that the size of the lipophilic chain presents a
strong correlation with the biological response.
The highest MIC and MFC values (250 and 2500 μg/mL)
were provided by compound 1. As this aminoalcohol has
the shortest carbon chain (eight carbons) among the mole-
cules described in this study, it could be suggested that the
increase in the lipophilic characteristic can hamper the
described pharmacological action, as demonstrated by [23].
In contrast, compound 3 exhibited the best activity among
the described aminoalcohols (MICs: 0.462–500 μg/mL) and
has 12 carbon atoms in its side chain; the result may be
Dermatomycoses are superficial infections that can trigger
inflammatory conditions and ulcerations [1–5]. This type of
mycosis is associated with several predisposing factors,
such as climatic conditions, sports activities, prolonged
contact with water, lifestyle, immunological status, chronic
diseases, and older age [6].
The main etiological agents of these infections are the
microorganisms oh the genera Trichophyton, Microsporum,
and Epidermophyton, which include the species T. rubrum,
T. mentagrophytes, E. floccosum, and M. canis [1, 4–7]. In
contrast, the genus Candida comprises opportunistic yeast
fungi whose representatives are responsible for causing
candidiasis, but it is also directly associated with dermato-
mycosis, with C. albicans being its primary representative
[8]. This species is also responsible for causing several
hospital infections from catheters and drains and compli-
cations of bacterial sepsis and the urinary system [9].
This type of mycosis is widely distributed among
humans and it is considered a serious health problem due to
the difficulty of treatment that is attributed to the reduced
efficacy of available drugs, prolonged treatment, and high
cost, in addition to causing hepatotoxicity. These factors
result in low adhesion to the drug therapy and consequently
the emergence of relapse cases and the selection of strains
more resistant to the antifungals [3, 10–12].
The search for compounds with biological activities from
natural sources, biomolecules, metals, etc. has been going
on for a long time [12]. In this context, organic synthesis
plays a fundamental role in the development of new com-
pounds such as aminoalcohols and diamines with potential
antibacterial as was verified by [13–20]. In this way new
aminoalcohols and diamines were synthesized and descri-
bed by [15] and [21]. These compounds are the target of this
study, have already been evaluated against Mycobacterium
tuberculosis and Leishmania species [14, 15, 19], Escher-
ichia coli, and Pseudomonas aeruginosa; Trichomonas
vaginalis [22], Staphylococcus aureus, S. epidermidis,
Escherichia coli, Pseudomonas aeruginosa [23], and anti-
fungal activity against fungi of the genera Trichophyton,
Epidermophyton, and Candida [24].
The severals studies were carried out and promising
results for the mentioned molecules and their derivatives
arouse greater interest in the evaluation of their antifungal
activity in vitro against the primary species of dermatophytic
and yeast fungi responsible for causing dermatomycoses.
Results and discussion
All aminoalcohols and diamines exhibited fungicidal activity
against the five fungal strains evaluated in this study, with

Medicinal Chemistry Research
Table 1 In vitro antifungal
activity of amphiphilic
Compounds
Fungal strains
aminoalcohols and diamines
Trichophyton
mentagro-
phytes
Trichophyton-
rubrum CCT
5507
Epidermophyt- Candidaalbi-
Candida
albicans
Clinical
isolated
onfloccosum-
CCF
cans ATCC
10231
ATCC 11481
URM 1666
-IOC-3757
MIC
MFC MIC
MFC
MIC
MFC
MIC
MFC
MIC
MFC
1
500
1000
7.4
250
125
7.81
3.9
500
250
7.81
3.9
1000
500
1000
1000
1000
1250 2500
312.5 625
2
1.85
78
19
78
39
78
3
0.462 7.4
500
19
4.8
4.8
9.7
4.8
2.4
19
19
4
250
3.9
250
7.8
15.62 31.25 4.8
15.62 15.62 9.7
4.8
9.7
4.8
1.2
78
4.8
19
5
3.9
7.8
6
0.24
0.97
1.95
500
3.9
0.48
0.97
3.90
500
3.9
0.12
0.97
1.95
1.95
1.95
1.95
4.8
1.2
19
4.8
2.4
78
7
0.487 0.97
8
3.9
7.81
125
1.95
125
31.25 250
9
125
0.97
62.5
125
3.9
250
3.9
19
19
19
1250
2.4
156
312
78
10
2.4
78
2.4
78
2.4
78
11
3.9
250
125
125
500
12
31.25 125
31.25 31.25 125
39
156.2 19
13
1.95
0.03
0.25
8
1.95
0.03
0.25
64
3.9
0.19
1
7.81
0.19
4
15.62 125
9
19
0.6
NE
NE
NE
NE
78
Terbinafine
Ketoconazole
Itraconazole
Amorolfine
>480
>640
>64
>16
NE
ND
ND
ND
ND
NE
NE
NE
NE
NE
NE
125
0.33
NE
NE
NE
NE
500
3.33
NE
NE
NE
NE
312.5
0.8
2
64
2
4
0,5
NE
NE
1
Amphotericin B NE
Nystatin NE
NE
NE
NE
NE
NE
0.08
Results are expressed as μg mL−1
ND not determined (MIC > 1000 μg mL−1 or MIC > 5000 μg mL−1), NE not evaluated, MIC minimum
inhibitory concentration, MFC minimum fungicidal concentration
associated with the synergism between the lipophilic chain
and the aminoalcohol functional group [21].
rubrum CCT 5507 URM 1666; however, the E. floccosum
CCF-IOF-3757 strain showed unexpected behavior when
presenting MIC > 480 μg/mL.
All the molecules evaluated in this study exhibited fungi-
cidal action against E. floccosum CCF-IOF-3757 (MFC ≤
1000 μg/mL), a fact that indicates their great significance,
since this strain was considered resistant to the reference drugs
(ketoconazole [>640 µg/mL], itraconazole [>64 µg/mL], ter-
binafine [>480 µg/mL] and amorolfine [>16 µg/mL]) [32] used
in the treatment of dermatomycosis. However, this fact is
consistent with the studies of [7], which mention that cases of
resistance to antifungals are not common.
The antifungal activities of compounds 1–13 against C.
albicans were analyzed. Results showed that compounds 2–13
presented lower MIC and MFC values than amphotericin B (125
and 500 μg/mL, respectively) when tested against C. albicans
ATCC 10231. Conversely, all compounds (1–13) presented
higher MIC and MFC values than nystatin. This experiment was
performed in triplicate to confirm the results which repeat the
values described in the Table 1.
According to studies conducted by Ouf et al. [33] and
Miron et al. [34], the MIC values of terbinafine against the
clinical isolates of T. rubrum and E. floccosum were 4–8
and 0.25–4 μg/mL, respectively. In our work, we check that
T. rubrum CCT 5507 URM 1666 was more susceptible to
the same drug described (MIC = 0.19 μg/mL), whereas E.
floccosum CCF-IOF-3757 was resistant to the above-
mentioned allylamine (MIC > 480 μg/mL). The results are
not contradictory, since clinical strains were used [33, 34],
so it is expected that the MIC values are higher when
compared to standard strains. This fact was evidenced for T.
When tested against the clinical isolate, compounds 2–8,
10, 11, and 13 showed lower MIC and MFC values than
amphotericin B. These results are of great significance due
the current scenario wherein there is an increase in the
number of C. albicans isolates resistant to available drug
therapy [35]. Compared to nystatin antifungal activity, all
the molecules presented higher MIC and MFC values.
Therefore, the results shown in Table 1 are important
because these compounds may contribute to the develop-
ment of a candidate prototype for treating infections caused
by resistant fungal strains.

Medicinal Chemistry Research
Conclusion
pleomorphism; however, its authenticity was certified
through macroscopic and microscopic analyses.
This study demonstrated the fungicidal activity of a series of
aminoalcohols 1–4 and diamines 5–13 against T. menta-
grophytes ATCC 11481, T. rubrum CCT 5507 URM 1666,
E. floccosum CCF-IOF-3757, C. albicans ATCC 10231,
and a clinical isolate of C. albicans. Among the evaluated
compounds, diamine 6 and 7 presented the lowest MIC and
MFC values against dermatophytes and yeast, respectively.
These results can contribute to the synthesis and evaluation
of compounds with fungicidal potential against both fila-
mentous fungi and yeasts that cause dermatomycoses.
Antifungal activity
The MIC and the MFC values were established as described
by Clinical and Laboratory Standards Institute (CLSI)
[32, 38, 39].
Minimum inhibitory concentration
The MIC value was established according to the CLSI
protocols M38-A2, M27-A3, and M27-S4 [32, 38, 39], and
the analyses were performed in triplicate. Initially, the
filamentous fungi and yeasts were cultivated on Sabouraud
dextrose agar for 7 days (filamentous fungi) e 2 days
(yeasts). These colonies were used to prepare fungal sus-
pension from successive washes of the surface on the cul-
ture medium where the growth microorganism occurred.
The number of viable fungal structures (conidia, blas-
toconidia, and chlamydoconidia) in the suspensions was
analyzed using a spectrophotometer (Libra S12; Biochrom,
Cambourne, UK) at a wavelength of 530 nm and a trans-
mittance of 68–70% for filamentous fungi and 89–90% for
yeast [32, 38–40]. These transmittance ranges corresponded
to 2 × 105 − 2.5 × 106 CFU/mL for filmamentous fungi and
1–5 × 106 CFU/mL for yeasts. Subsequently, the suspension
was diluted in RPMI-1640 culture medium (Sigma, St.
Louis, MO, USA) buffered with 3-(N-morpholino)propa-
nesulfonic acid (MOPS; JT Baker, Griesheim, Germany), at
a ratio of 1:50 (final concentration of 0.4–5.0 × 104 CFU/mL
for filamentous fungi) and 1:2000 (final concentration of
1–5 × 103 CFU/mL for yeast).
Material and methods
Chemistry
N-alkylated aminoalcohols 1–4 and diamines 5–13 (Scheme
1) were prepared using a methodology previously described
by [15, 25] (Scheme 1).
Fungal strains
Three strains of filamentous fungi, T. mentagrophytes
ATCC 11481, T. rubrum CCT 5507 URM 1666, and E.
floccosum CCF-IOF-3757, were obtained from the Collec-
tion of Tropical Crops (CCT) provided by the André
Tosello Foundation (Campinas-SP, Brazil). C. albicans
ATCC 10231 was provided by the National Institute of
Quality Control in the Health-Oswaldo Cruz Foundation
(Rio de Janeiro-RJ, Brazil) and a clinical isolate of this
species was obtained from a patient form Maurílio Baldi
Laboratory at the UFJF University Hospital.
The authenticity of the lineages T. mentagrophytes
ATCC 11481, T. rubrum CCT 5507 URM 1666, C. albi-
cans ATCC 10231, and the clinical isolate of C. albicans
was confirmed through molecular analysis as described
previously [24, 36, 37]. The strain of E. floccosum exhibited
The aminoalcohols 1–4 and the diamines 5–13 were
solubilized in RPMI-1640 culture medium, buffered with
MOPS, and tested at the final concentrations of 7.8–1000
and 39.06–5000 µg mL−1 for filamentous fungi and yeasts,
respectively. Fungal growth was evaluated by adding
100 µL RPMI-1640 culture medium buffered with MOPS
Scheme 1 Synthesis of
aminoalcohols 1–4 and diamines
5–13

Medicinal Chemistry Research
containing the fungal inoculum. The 96-well sterile plates
were incubated at 28 2 °C for 7 days (dermatophytes) or at
37 2 °C for 48 h (yeasts) according to the CLSI. The
growth of the fungi was analyzed visually using a SMZ800
microscope (Nikon, Melville, NY). Terbinafine, ketocona-
zole, itraconazole, amorolfine, amphotericin B, and nystatin
were used as reference drugs and assessed according to the
M38-A2, M27-A3, and M27-S4 protocols [32, 38, 39].
5. Zhang J, Tan J, He Y. Tacrolimus, not triamcinolone acetonide,
interacts synergistically with itraconazole, terbinafine, bifonazole,
and amorolfine against clinical dermatophyte isolates. J Med
Mycol. 2018;28:612–6. https://doi.org/10.1016/j.mycmed.2018.
09.003.
6. Silva-Rocha WP, De Azevedo MF, Chaves GM. Epidemiology
and fungal species distribution of superficial mycoses in Northeast
Brazil. J Med Mycol. 2017;27:57–64. https://doi.org/10.1016/j.
mycmed.2016.08.009.
7. Achterman RR, White TC. A foot in the door for dermatophyte
research. PLoS Pathog. 2012;8:6–9. https://doi.org/10.1371/
journal.ppat.1002564.
Minimum fungicidal concentration
8. Silva RAC, Da Silva CR, Neto JBA, Da Silva AR, Campos RS,
Sampaio LS, et al. In-vitro anti-Candida activity of selective
serotonin reuptake inhibitors against fluconazole-resistant strains
and their activity against biofilm-forming isolates. J Micro Path.
2017;107:341–8. https://doi.org/10.1016/j.micpath.2017.04.008.
9. Wiebusch L, Almeida-Apolonio AA, Rodrigues LMC, Bicudo
BP, Silva DBS, Lonchiati DF, et al. Candida albicans isolated
from urine: phenotypic and molecular identification, virulence
factors and antifungal susceptibility. Asian Pac J Trop Biomed.
2017;7:624–8. https://doi.org/10.1016/j.apjtb.2017.06.006.
10. Millsop JW, Fazel N. Oral candidiasis. Clin Dermatol.
2016;34:487–94. https://doi.org/10.1016/j.clindermatol.2016.02.
022.
11. Carmello JC, Alves F, Mima EGO, Jorge JH, Bagnato VS,
Pavarina AC. Photoinactivation of single and mixed biofilms of
Candida albicans and non-albicans Candida species using
Phorodithazine®. Photodiagnosis Photodyn Ther. 2017;17:194–9.
https://doi.org/10.1016/j.pdpdt.2016.11.013.
12. Rehman S, Gunday ST, Alsalem ZH, Bozkurt A. Synthesis and
characterization of novel azole functionalized poly(glycidyl
methacrylate)s for antibacterial and anticandidal activity. Curr Org
Synth. 2019;16:1002–9. https://doi.org/10.2174/13852728236
66190828112113.
The MFC analysis for filamentous fungi was performed by
transferring 10 μL volume from the wells where no fungal
growth was observed to the wells of another microtiter plate
containing 200 µL of Sabouraud dextrose broth (SDB)
sterile and without antifungal SDB as described previously
[41]. The MFC was determined as the lowest concentration
of the molecule that resulted in fungal death. The MFC for
C. albicans was evaluated using 5 µL from wells without
fungal growth, which was transferred to cryotubes con-
taining 1000 µL SDB. The analysis was conducted as
described above [42].
Acknowledgements This research was supported by Coordination for
the Improvement of Higher Education Personnel (CAPES), National
Council for Scientific and Technological Development (CNPq),
Research Support Foundation of the State of Minas Gerais (FAPE-
MIG), Carlos Chagas Filho Foundation for Research Support of the
State of Rio de Janeiro (FAPERJ-E-26/202.447/2019), and Pro-
Rectorate of Graduate Studies and Research at the Federal University
of Juiz de Fora (PROPESQ/UFJF).
13. Almeida AM, Oliveira BA, Castro PP, Mendonça CC, Furtado
RA, Nicolella HD, et al. Lipophilic gold (I) complexes with 1, 3,
4-oxadiazol-2-thione or 1, 3-thiazolidine-2-thione moieties:
synthesis and their cytotoxic and antimicrobial activities. Bio-
metals. 2017;30:841–57. https://doi.org/10.1007/s10534-017-
0046-6.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
14. Coimbra ES, Santos JÁ, Lima LL, Machado PA, Campos DL,
Pavan FR, et al. Synthesis, antitubercular and leishmanicidal
evaluation of resveratrol analogues.
J Braz Chem Soc.
Publisher’s note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.
2016;27:2161–9. https://doi.org/10.5935/0103-5053.20160107.
15. Rezende CO Jr, Le Hyaric M, Da Costa CF, Corrêa TA, Taveira
AF, Araújo DP, et al. Preparation and antitubercular activity of
lipophilic diamines and amino alcohols. Mem do Inst Oswaldo
Cruz. 2009;104:703–5. https://doi.org/10.1590/S0074-02762009
000500006.
References
16. Rezende CO Jr, Alves RO, Rezende CAM, Da Costa CF, Silva H,
Le Hyaric M, et al. Trypanocidal activity of lipophilic diamines
and amino alcohols. Biomed Pharmacother. 2010;64:624–6.
https://doi.org/10.1016/j.biopha.2010.06.002.
17. Giordani RB, De Almeida MV, Fernandes E, Costa CF, De Carli
GA, Tasca T, et al. Anti-Trichomonas vaginalis activity of syn-
thetic lipophilic diamine and amino alcohol derivatives. Biomed
Pharmacother. 2009;63:613–7. https://doi.org/10.1016/j.biopha.
2008.10.002.
18. Popadyuk II, Markov AV, Babich VO, Salomatina OV, Loga-
shenko EB, Zenkova MA, et al. Novel derivatives of deoxycholic
acid bearing aliphatic or cyclic diamine moieties at the C-3
position: synthesis and evaluation of anti-proliferative activity.
Bioorg Med Chem Lett. 2017;27:3755–9. https://doi.org/10.1016/
j.bmcl.2017.06.072.
1. Achterman RR, White TC. Dermatophytes. Curr Biol.
2013;23:551–2. https://doi.org/10.1016/j.cub.2013.03.026.
2. Chen J, Yi J, Liu L, Yin S, Chen R, Li M, et al. Substrate
adaptation of Trichophyton rubrum secreted endoproteases. J
Micro Path. 2010;48:57–61. https://doi.org/10.1016/j.micpath.
2009.12.001.
3. Sadeghi-Nejad B, Rezaei-Matehkolaei A, Naanaie SY. Isolation and
antifungal activity evaluation of Satureja khuzestanica Jamzad extract
against some clinically important dermatophytes. J Myco Med.
2017;27:554–60. https://doi.org/10.1016/j.mycmed.2017.08.002.
4. Trocoli Drakensjö I, Vassilaki I, Bradley MM. Granuloma caused
by Trichophyton mentagrophytes in 2 immunocompetent patients.
Actas Dermo-Sifiliogr. 2017;108:e6–8. https://doi.org/10.1016/j.
ad.2015.05.020.

Medicinal Chemistry Research
19. Taveira AF, Le Hyaric M, Reis EFC, Araújo DP, Ferreira AP, De
Souza MA, et al. Preparation and antitubercular activities of
alkylated amino alcohols and their glycosylated derivatives.
Bioorg Med Chem Lett. 2007;15:7789–94. https://doi.org/10.
1016/j.bmc.2007.08.045.
20. Wang D, Liu W, Tang M, Yu N, Yang X. Atroposelective synthesis of
biaryl diamines and amino alcohols via chiral phosphoric acid catalyzed
para-aminations of anilines and phenols. iScience. 2019;22:195–205.
https://doi.org/10.1016/j.isci.2019.11.024.
21. Fernandes FS, Fernandes TS, Silveira LS, Caneschi W, Lourenço
MCS, Diniz CG, et al. Synthesis and evaluation of antibacterial
and antitumor activities of new galactopyranosylated amino
alcohols. Eur J med Chem. 2016;108:203–10. https://doi.org/10.
1016/j.ejmech.2015.11.037.
22. Rigo GV, Trein MR, Trentin DS, Macedo AJ, De Olivera BA, De
Almeida AM, et al. Diamine derivative anti-Trichomonas vagi-
nalis and anti-Tritrichomonas foetus activities by effect on poly-
amine metabolism. Biomed Pharmacother. 2017;95:847–55.
https://doi.org/10.1016/j.biopha.2017.09.007.
23. De Almeida AM, Nascimento T, Ferreira BS, Castro PP, Silva
VL, Diniz CG, et al. Synthesis and antimicrobial activity of novel
amphiphilic aromatic amino alcohols.Bioorg Med Chem Lett.
2013;23:2883–7. https://doi.org/10.1016/j.bmcl.2013.03.078.
24. Caneschi CA, Almeida AM, Martins FJ, Le Hyaric M, Oliveira
MME, Macedo GC, et al. In vitro antifungal activity of organic
compounds derived from amino alcohols against onychomycosis.
Braz J Microbiol. 2017;48:476–82. https://doi.org/10.1016/j.bjm.
2016.12.008.
25. Sales PA Jr, Júnior COR, Le Hyaric M, De Almeida MV,
Romanha AJ. The in vitro activity of fatty diamines and amino
alcohols against mixed amastigote and trypomastigote Trypano-
soma cruzi forms. Mem do Inst Oswaldo Cruz. 2014;109:362–4.
https://doi.org/10.1590/0074-0276130496.
26. Du P, Viswanathan UM, Xu Z, Ebrahimnejad H, Hanf B, Bur-
kholz T, et al. Synthesis of amphiphilic seleninic acid derivatives
with considerable activity against cellular membranes and certain
pathogenic microbes. J Hazard Mater. 2014;269:74–82. https://
doi.org/10.1016/j.jhazmat.2014.01.014.
27. Schreier S, Malheiros SVP, De Paula E. Surface active drugs: self-
association and interaction with membranes and surfactants.
Physicochemical and biological aspects. Biochim et Biophys
Acta. 2000;1508:210–34. https://doi.org/10.1016/s0304-4157(00)
00012-5.
decahydroisoquinolines: novel antifungals that target ergosterol
biosynthesis. Arch Pharm. 2014;347:283–90. https://doi.org/10.
1002/ardp.201300338.
31. Tang H, Wu J, Zhang W, Zhao L, Zhang Y, Shen C. Design,
synthesis and biological evaluation of novel non-azole derivatives
as potential antifungal agents. Chin Chem Lett. 2015;26:2–6.
https://doi.org/10.1016/j.cclet.2015.04.030.
32. Clinical and Laboratory Standards Institute (CLSI). Reference
method for broth dilution antifungal susceptibility testing of fila-
mentous fungi: approved standard. 2nd edn. (M38-A2). Wayne,
PA, USA: Clinical and Laboratory Standards Institute; 2008.
p. 1–35.
33. Ouf SA, Abu Taleb AM, Tharwat NA, Geweely NS. Efficacy of
some synthesized thiazoles against dermatophytes. J Mycol Med.
2013;23:230–23. https://doi.org/10.1016/j.mycmed.2013.07.056.
34. Miron D, Battisti F, Silva FK, Lana AD, Pippi B, Casanova B,
et al. Antifungal activity and mechanism of action of mono-
terpenes against dermatophytes and yeasts. Braz J Pharmacogn.
2014;24:660–7. https://doi.org/10.1016/j.bjp.2014.10.014.
35. Szczepaniak J, Cieslik W, Romanowicz A, Musiol R, Krasowska
A. Blocking and dislocation of Candida albicans Cdr1p trans-
porter by styrylquinolines. Int
J
Antimicrob Agents.
2017;50:171–6. https://doi.org/10.1016/j.ijantimicag.2017.01.044.
36. Bisha B, Kim HJ, Brehm-Stecher BF. Improved DNA-FISH for
cytometric detection of Candida spp.
J
Appl Microbiol.
2011;110:881–92. https://doi.org/10.1111/j.1365-2672.2011.04936.x.
37. Rivas L, Mühlhauser M. Complejo Trichophyton mentagrophytes.
Rev Chil Infect. 2015;32:319–20. https://doi.org/10.4067/S0716-
10182015000400009.
38. Clinical and Laboratory Standards Institute (CLSI). Reference
method for broth dilution antifungal susceptibility testing of
yeasts; Third informational supplement. CLSI document M27-S3.
Wayne, PA, USA: Clinical and Laboratory Standards Institute;
2008.
39. Clinical and Laboratory Standards Institute (CLSI). Reference
method for broth dilution antifungal susceptibility testing of yeast;
fourth informational supplement. CLSI document M27-S4.
Wayne, PA, USA: Clinical and Laboratory Standards Institute;
2012.
40. Falahati M, Nozari S, Makhdoomi A, Ghasemi Z, Nami S, Assadi
M. Comparison of antifungal effect of nanosilver particles alone
and in combination with current drugs on candida species isolated
from women with recurrent vulvovaginal candidiasis. Eur J Exp
Biol. 2014;4:77–82.
41. Magagnin CM, Stopiglia CDO, Vieira FJ, Daiane H, Machado M,
Vetoratto G, et al. Perfil de suscetibilidade a antifúngicos de
dermatófitos isolados de pacientes com insuficiência renal crônica.
Bras Dermatol. 2011;86:694–701. https://doi.org/10.1590/S0365-
05962011000400011.
42. Espinel-Ingroff A, Fothergill A, Peter J, Rinaldi MG, Walsh TJ.
Testing conditions for determination of minimum fungicidal con-
centrations of new and established antifungal agents for Aspergillus
spp.: NCCLS Collaborative Study. J Clin Microbiol. 2002;40:3204–8.
https://doi.org/10.1128/jcm.40.9.3204-3208.2002.
28. Lima MIO, Medeiros ACA, Silva KVS, Cardoso GN, Lima EO,
Pereira FO. Investigation of the antifungal potential of linalool
against clinical isolates of fluconazole resistant Trichophyton
rubrum. J Mycol Med. 2017;27:195–202. https://doi.org/10.1016/
j.mycmed.2017.01.011.
29. Peres NT, Maranhão FCA, Rossi A, Martinz-Rossi NM. Derma-
tófitos: Interação patógeno-hospedeiro e resistência a antifúngicos.
Bras Dermatol. 2010;85:657–67. https://doi.org/10.1590/S0365-
05962010000500009.
30. Krauss J, Muller C, Kiebling J, Richter S, Staudacher V, Bracher
F. Synthesis and biological evaluation of novel N-alkyl tetra- and