Acta Ecologica Sinica 42 (2022) 461–466

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Acta Ecologica Sinica

journal homepage: www.elsevier.com/locate/chnaes

Anticandidal activity of dichloromethane extract obtained from the red

algae A. armata of the Algerian coast
Ilhem Messahli a, Hicham Gouzi a, *, Ibrahim Sifi b, Rachid Chaibi a, Asma Rezzoug a,
Linda Rouari a
a
Laboratoire des Sciences Biologiques et Agronomiques (LSBA), Faculté des Sciences, Université Amar Télidji, Route de Ghardaïa BP37G (03000), Laghouat, Algeria
b
Laboratoire des Sciences Fondamentales à l'Université Amar Télidji, Route de Ghardaïa BP37G (03000), Laghouat, Algeria

A R T I C L E I N F O A B S T R A C T

Keywords: This work reports for the first time the anticandidal activity of the dichloromethane (DCM) extract from the
Antifungal activity Algerian invasive red marine algae A. armata Harvey. In a preliminary assessment, the DCM extract was screened
A. armata for its antifungal activity against two strains of Candida albicans, namely (IP 444) and (ATCC 10231). As a well-
Candida albicans
established approach, the anticandidal activity was expressed as zone of inhibition by agar well and disk
Dichloromethane extract
diffusion methods. The minimum inhibitory concentration (MIC) was also determined for the two fungal strains.
Within this framework, the DCM extract of the red algae A. armata has a strong inhibition effect against the
considered Candida albicans strains. In addition, Candida albicans IP444 (MIC = 0.58 mg/mL) was more sensitive
to DCM algal extract when compared to Candida albicans ATCC 10231 (MIC = 2.34 mg/mL). GC–MS analysis
suggested that brominated compounds and fatty acids are responsible for anticandidal activity of dichloro­
methane extract of A. armata. These preliminary results may constitute a future applied of lipophilic extract of
the red algae A. armata as a promising source of natural compounds with antifungal properties.

1. Introduction antifungal agents are unavoidable [5–7]. Furthermore, the current

Fungi are one of great ubiquitous living organisms, they are relevant
constituents of most ecosystems including soil and living beings [1,2].
Most of them are inoffensive, since they are part of the commensal flora
of the host. However, under certain unfavourable conditions, opportu­
nistic species can propagate into the bloodstream. As a result, in
immunocompromised hosts, invasive opportunistic fungal infections
thrive very slowly causing fatal sepsis [1,3]. In Algeria, one of the most
growing threats to human health is fungal infection. At least 568,900
(1.41%) of Algerians have a serious fungal infection each year, affecting
people of all ages [4]. Of particular concern is the incidence of fungal
infections by Candida albicans; a commensal dimorphic colonizer of
vaginal mucosal surfaces and gastro-intestinal tract present in any
healthy individual, but also ranked among the top four leading causes of
haematogenous infections [2].
Despite the limited available pharmaceutical arsenal, there has been
an ongoing quest for new and novel antifungal compounds, because
evidence shows that development and spread of resistance to any new
therapeutic choices for the treatment of fungal infections caused by
pathogen species like C. albicans are typically associated with severe
adverse effects and drawbacks, particularly in terms of toxicity, unde­
sirable drug interactions, spectrum of activity and safety [6–10]. This
underscores the critical need to broaden the spectrum of the currently
available antifungal drugs. Thus, new options including unconventional
new sources of bioactive natural products for successful antifungal
therapy have to be explored [11].
It is widely recognized that nearly all of the current natural product-
derived therapeutics have terrestrial origins. However, a number of
studies show that marine environment is a valuable source of both
biological and chemical diversity, encompassing a wide and yet not fully
known naturally occurring biologically active compounds [12–15]. Of
particular importance, red marine algae have been recognized as a rich
source of new and unusual organic molecules with diverse biological
properties [16]. Among the red algae, Asparagopsis species (Bonnemai­
soniales, Rhodophyta) like A. armata and Asparagopsis taxiformis,
showed potent antifungal, antibacterial and antioxidant attributes

* Corresponding author.
E-mail addresses: i.messahli@lagh-univ.dz (I. Messahli), h.gouzi@lagh-univ.dz (H. Gouzi), i.sifi@lagh-univ.dz (I. Sifi), r.chaibi@lagh-univ.dz (R. Chaibi), a.
rezzoug@lagh-univ.dz (A. Rezzoug), l.rouari@lagh-univ.dz (L. Rouari).

https://doi.org/10.1016/j.chnaes.2021.08.005
Received 14 August 2020; Received in revised form 24 July 2021; Accepted 17 August 2021
Available online 26 August 2021
1872-2032/© 2021 Ecological Society of China. Published by Elsevier B.V. All rights reserved.
I. Messahli et al.
[17–19].
Recently, Grimes et al. [20] carried out a thorough analysis of the
recorded marine species introduced along the Algerian coast from 1834
to December 2017. The authors clearly showed that A. armata was
among five alien species that constitute 34.5% of the introduced species
observed along the Algerian coast. A. armata was first discovered on the
western and central coasts of Algeria, but since 2003, it has been also
reported from several ecosystems along the Algerian coast [20].
A. armata is actually considered to be one of the worst true alien and
range-expanding bio-invasive species, threating biodiversity and native
marine ecosystems of the Algerian coastline and the Mediterranean Sea
[19–22].
Fortunately, previous studies have primarily stated the importance
of adding value to the abundant biomass of the invasive macroalgae
species like A. armata [21]. Indeed, a commercial value could overcome
the unaffordable costs and the elusive ways related to their spread
control [21]. Typically, valorization and exploitation of biomass derived
from these species may have a substantial positive effect both on the
economic development and on socio-economic revenue by providing a
sustainable source of bioactive compounds, while preserving the integ­
rity of the marine ecosystems [21,23]. Nevertheless, to the best of our
knowledge, no attempt was done to explore the potential antifungal
activity of the red marine algae A. armata collected from the Algerian
coastline. Furthermore, several studies showed the antimicrobial
Fig. 1. Map showing the collection site in the west coast of Algeria (Salamandre village at Mostaganem) (35◦ 35′ 54′′ N, 0◦ 0′ 3′′ E).
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Acta Ecologica Sinica 42 (2022) 461–466
activity of aqueous or very polar extracts of red algae but it is uncommon
to find antimicrobial activity for their lipophilic extracts [24]. Realizing
the gap in the extant literature, this study attempts to provide a pre­
liminary investigation regarding the potential anticandidal activity of
the dichloromethane extract of A. armata against C. albicans. This may
lead to favourable economic and ecological impacts and offers unique
opportunity to overcome the usual limitations and difficulties related to
its spread control.
2. Materials and methods
2.1. Collection and identification of algae
Samples of the red algae A. armata Harvey were collected in March
2019 by hand picking from the Western Mediterranean coast of Algeria,
in Mostaganem village (Salamandre) (coordinates 35◦ 35′ 54“N latitude,
0◦ 0’3”E longitude) (Fig. 1) at a 1-m maximum depth dive. A voucher
specimen was authenticated by Prof. Hicham GOUZI and deposited at
the Department of Biology, University of Laghouat. The fresh algae was
rinsed out in seawater and thoroughly cleaned of sand particles, epi­
phytes and exogenous matters. The clean material was then transferred
to the laboratory in plastic bags, air-dried at room temperature for two
weeks and ground until reaching fine powder using a mortar.
I. Messahli et al.
2.2. Preparation of dichloromethane extract
Dry material (10 g) was extracted with 100 mL of dichloromethane
for 24 h under stirring condition (250 rpm) at room temperature. After
filtration (Whatman sterile filter paper No. 1), the solutions were pooled
and concentrated to dryness at 45 ◦ C under vacuum on a rotary evap­
orator (Buchirotavapor R-200, Germany) to yield the crude extract that
represents 2.2% of the algal dry weight. The dry brown residue (0.22 g)
was than solubilized in dimethyl sulfoxide (DMSO) (Sigma, Steinheim,
Germany) at 300 mg/mL. The obtained solution also called dichloro­
methane (DCM) extract was stored at 4 ◦ C until further use.
2.3. Candida strains and culture conditions
Two reference strains, Candida albicans (IP 444) and Candida albicans
(ATCC 10231) were used for the tests in this study and they were pro­
vided by the Laboratory Antibiotics Antifungals: Physico-Chemical,
Synthesis and Biological Activity (LapSab) (Tlemcen University,
Algeria). For the storage, yeast strains were cultured and maintained on
Sabouraud Dextrose Agar (SDA) until the next steps.
2.4. Evaluation of anticandidal activity
The sensitivity of Candida albicans strains was evaluated using
nystatin as a reference antifungal. Nystatin and algal extract were pre­
pared at different concentrations with DMSO as a solvent. In vitro anti­
candidal susceptibility assays of the algal extract and nystatin were
performed using the standardized disk and well diffusion methods. For
the disk diffusion method, Whatman No. I filter paper disk of 6 mm
diameter was sterilized by autoclaving for 20 min at 120 ◦ C. The sterile
disks were impregnated with 10 μL of different concentrations of the
algal extract or nystatin and then placed with suitable space on the
sabouraud agar medium previously inoculated with a suspension of 0.1
DO620nm of Candida albicans (106–108 CFU / mL). The yeast inoculum
suspensions were prepared in sterile salt solution from 24 h cultures on
SDA at 37 ◦ C. One of the disks is impregnated with DMSO (99.99%) only
serving as a negative control. After pre-diffusion, the plates were incu­
bated at 37 ◦ C for 48 h.
For the well diffusion method, wells of 6 mm in diameter were
punched out using sterile Pasteur pipettes in sabouraud agar plates
inoculated with herein studied Candida albicans strains. 40 μL of the
different concentrations of algal extract or nystatin were transferred into
each well. Once again, DMSO was used as a negative control. The plates
thus prepared were incubated for 48 h at 37 ◦ C.
The inhibition zone diameter for each disk and well was measured by
a calliper and the anticandidal activity was classified from less active
(<10 mm), moderately active (<15 mm) and to highly active (>15 mm)
[25,26]. The experiments were carried out in duplicates and data were
expressed in millimetres as mean values ± SD.
2.5. Minimal inhibitory concentration (MIC)
The minimal concentration of nystatin and dichloromethane algal
extract that inhibit the growth of the yeast Candida albicans (MIC) was
determined using the microdilution method. The suspension of each
strain was prepared in Sabouraud Dextrose Broth (Condalab, Madrid,
Spain) supplemented with 1% Tween 80 from 24 h cultures and then
adjusted to 105 CFU/mL. 150 μL of each strain suspension culture was
added into 96 well microtitre plates (Corning Incorporated Costar®,
USA) containing dilutions of algal extract over the concentration range
of 8.55 × 10− 6-37.5 mg/mL. To get deeper insights on the minimal
inhibitory concentration of the studied algal extract, positive control
wells containing nystatin at different concentrations ranging from 2.03
× 10− 5 mg/mL to 6.25 mg/mL and additional negative control wells
involving DMSO instead of the algal extract were also included. The well
microtiter plates of each strain of Candida albicans containing different
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Acta Ecologica Sinica 42 (2022) 461–466
diluted samples of algal extract, positive and negative controls were then
incubated at 37 ◦ C for 24 h. The minimal inhibitory concentration was
visually checked for each well through evaluation of yeast growth in­
hibition in comparison with growth controls wells.
3. Results
A variety of solvents (methanol, dichloromethane, hexane and
acetone) have been used to screen the anticandidal activity of A. armata
extract. Our findings revealed that DCM extract exhibited the highest
antifungal activity against the two strains of Candida albicans compared
with the other tested solvents (data not shown). As shown in Fig. 2,
inhibition of the fungal growth was in a mass concentration-dependent
manner with best correlation (R2 = 0.92–0.99) as determined by the
well diffusion and disk diffusion techniques.
Tables 1 and 2 illustrate the results obtained from the anticandidal
screening assays of nystatin and dichloromethane extract of the red
marine algae A. armata determined by agar diffusion methods. The data
are quite revealing in several ways. First, alongside to the well diffusion
method, the disk diffusion method gives strong evidence of algal
bioactive compounds. Hence, their anticandidal activity can be estab­
lished. The obtained results show that by far, large inhibition zones
ranging from 44.11 to 55 mm (19.29 to 23.50 mm) (Fig. 3) can be ob­
tained with concentrations ranging from 6 mg/well to 12 mg/well (1.5
mg/disk to 3 mg/disk) of the DCM extract on C. albicans ATCC 10231
determined by the well diffusion method (disk diffusion method). On the
other hand, highest inhibition activity was shown in C. albicans IP444
with total inhibition at 1.2 mg/well determined by the well diffusion
method (See Table 2). According to our results, dichloromethane extract
of the red marine algae A. armata has the lowest inhibition at 0.135 mg/
disk determined by the disk diffusion method in C. albicans IP 444. (See
Table 1.)
All concentrations of nystatin showed an activity against the fungal
strains with inhibition zones going from 13.2 to 31.5 mm for C. albicans
ATCC 10231 and from 15 to 37.3 mm for C. albicans IP 444. On the other
hand, the growth inhibition effect was not observed in any of the
analyzed DMSO samples, thereby demonstrating that DMSO has no
anticandidal activity.
The DCM algal extract generated a MIC of 0.58 mg/mL against
C. albicans ATCC 10231 and it demonstrated a somewhat higher MIC of
2.34 mg/mL against C. albicans IP444.
The MIC values of nystatin resulted in 2.03 × 10− 5 and 8.12 × 10− 5
mg/mL for C. albicans (ATCC 10231) and C. albicans (IP444),
respectively.
4. Discussion
Starting with the experimental evidence of a low chemical extraction
yield of dichloromethane, our result is in the lines of earlier literature.
The extraction yield of four solvents, namely dichloromethane, hexane,
water and Methanol from the red marine algae Asparagopsis taxiformis
was analyzed by Machado et al. [27]. The authors showed that
dichloromethane and hexane have the lowest extraction yields (1.9%)
and (0.5%) respectively compared to water (24.9%) and Methanol
(10.2%). In addition, the anticandidal activity of algal extract was
significantly affected by the type of extracting solvent which was related
to the recovery yields of bioactive compounds. Of the solvents used,
dichloromethane extracted the highest total amount of antifungal
compounds from A. armata. Another interesting research conducted by
Guedes et al. [17] reported very similar dichloromethane extraction
yields from the red marine algae Hypnea musciformis (2.58%) which
exhibits a high antifungal activity against species of dermatophytes and
C. albicans. Besides, it has been well established that the variability of
the extraction yield is inherently linked to many factors, with the solvent
polarity and the chemical properties of the sample being the most
important factors under the same experimental conditions [28,29].
I. Messahli et al. Acta Ecologica Sinica 42 (2022) 461–466

Fig. 2. Linear correlation between mass concentration (in mg/disk for a and b; in mg/well for c and d) and the anticandidal activity of DCM algal extracts expressed
as diameter of growth zone inhibition (mm).

Table 1
Antifungal activities (disk-diffusion technique) classified according to the
diameter of the inhibition zone around the point of application of the sample.
The average of the yeast inhibition zones is expressed in millimetres.
Mass concentrations (mg/disk) Inhibition zones diameters (mm)
Table 2
Antifungal activities (well-diffusion technique) classified according to the
diameter of the inhibition zone around the point of application of the sample.
The average of the yeast inhibition zones is expressed in millimetres.
Mass concentrations (mg/well) Inhibition zones diameters (mm)

C. albicans ATCC C. albicans C. albicans ATCC C. albicans

10231 IP444 10231 IP444

Nystatin 0.10 31.51 ± 0.15 37.32 ± 0.66 Nystatin 0.40 33.80 ± 1.00 31.76 ± 0.83
2.00 × 21.37 ± 1.25 22.59 ± 0.76 8.00 × 26.26 ± 0.76 26.35 ± 1.38
10− 3 10− 3
4.00 × 15.85 ± 0.96 21.49 ± 1.44 1.60 × 12.46 ± 0.30 15.53 ± 0.79
10− 4 10− 3
8.00 × 15.56 ± 0.49 16.07 ± 1.04 3.20 × 10.55 ± 0.24 11.91 ± 0.00
10− 5 10− 4
3.20 × 13.25 ± 0.24 15.00 ± 0.72 1.28 × 6.00 ± 0.00 9.41 ± 0.88
10− 6 10− 5
Dichloromethane 3.00 23.50 ± 0.74 20.0 ± 0.61 dichloromethane 12.0 55.00 ± 0.50 TIa
extract 1.50 19.29 ± 0.92 12.52 ± 0.25 extract 6.00 44.11 ± 1.07 45.75 ± 0.37
0.45 10.27 ± 0.72 10.52 ± 0.07 1.80 9.73 ± 0.57 20.13 ± 0.70
1.35 × 7.06 ± 0.09 6.61 ± 0.14 0.54 6.00 ± 0.00 6.00 ± 0.00
10− 1 0.16 6.00 ± 0.00 6.00 ± 0.00
4.00 × 6.00 ± 0.00 6.00 ± 0.00 a
10− 2 TI: Total inhibition.

The data in Tables 1 and 2, suggest that the well diffusion method
claims better performance than the disk diffusion method. As was pre­
viously established by Valgas et al. [30], the evidence we found further
supports the fact that the well diffusion method would be more suitable
for screening suspensions of dichloromethane algal extracts.
Turning now to the remarkable anticandidal activity of the DCM
extract, our findings appear to be well substantiated by the growing
body of literature that has demonstrated the high efficiency of the ex­
tracts from the red marine algae genus including A. armata against a
broad spectrum of test pathogens [21,25,27,31–33].
According to Salvador et al. [31], the methanolic extract (at 200 mg/
well) of A. armata Harvey collected from Iberian coast showed an in­
hibition zone of 53.2 mm against Candida albicans (ATCC 48867).
Drawing on an extensive range of 82 red, brown and green marine algae
species, the authors were able to show that the red marine algae genus

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I. Messahli et al.
Fig. 3. Results of antifungal activity of DCM extract of A. armata on C. albicans obtained by (a, b and c) well diffusion method and (d, e and f) disk diffusion method
(T: temoins (DMSO)).
including A. armata had both the highest values and the broadest
spectrum of bioactivity. In their experiments intended to study the
antimicrobial potential and the seasonality of 15 red marine algae spe­
cies collected from the Southwest coast of India, Manilal et al. [32]
outlined the anticandidal activity of the methanolic extracts of
A. taxiformis. Three species of candida where studied of which
C. albicans showed zones of inhibition ranging from 14 to 25 mm.
Another study conducted by Saidani et al. [33] has established that the
crude methanolic extract (12.48 mg/mL) of the red marine algae Rho­
domela confervoides from the East coast of Algeria (Bejaia) may show
significant inhibition effect on Candida albicans (inhibition zone of 24
mm).
It seems that the anticandidal activity of methanolic extracts from
the aforementioned red marine algae species, are by far less significant
compared to the Asparagpsis armata DCM extract from the present study.
Therefore, our results are promising and should be validated by a larger
sample size. Nevertheless, we should sound a note of caution with regard
to such findings, since there are too many factors which may explain the
outcomes of different investigations such as the stage of active growth,
sexual maturity of the studied algae, ecological factors (nutrients and
irradiance), seasonal variations and the extraction protocols [31,32,34].
The pungent aroma of A. armata is attributed to its high content of
lipophilic halogenated compounds such as bromoform, bromine ethane,
halomethanes and to some extent to other small molecules like chlorine,
acetaldehydes, acetone, epoxypropanes, acroleins, butenones
[19,35–39]. Among these chemicals, bromoform which expresses potent
antimethanogenic activity was reported to be responsible for the anti­
candidal activity of the dichloromethane extracts from A. armata [27].
The MIC values of the dichloromethane algal extract and nystatin give
evidence to a somewhat higher sensitivity levels to nystatin, which re­
mains the most effective antifungal on Candida albicans. This is not
surprisingly due to the low purity of the antifungal bioactive compounds
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Acta Ecologica Sinica 42 (2022) 461–466
in the crude algal extract, which consists of many compounds.
Further analysis of MICs show that the dichloromethane algal extract
trend to perform better on C. albicans ATCC 10231 than on C. albicans
IP444, thereby demonstrating that C. albicans ATCC 10231 is somewhat
more sensitive to DCM algal extract than C. albicans IP 444.
5. Conclusion
The present study was designed to assess the anticandidal activity of
the dichloromethane extract from the red marine algae A. armata. It has
gone some way towards the valorization and exploitation of biomass
from this invasive macroalgae of the west coast of Algeria and Medi­
terranean Sea by obtaining added-value bioactive compounds. For the
first time, the relevance of the anticandidal activity of the dichloro­
methane extract from the studied species of A. armata is clearly
demonstrated using the microdilution and the agar diffusion methods.
Yet, taken together, our findings warrant further researches on the
dichloromethane extract containing lipophilic compounds from the red
marine algae A. armata as a potential anticandidal including both
isolation, purification, identification of the natural bioactive compounds
and investigating the toxicity of the bioactive compounds before any
effective clinical application.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
I. Messahli et al. Acta Ecologica Sinica 42 (2022) 461–466

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