Progress in the Chemistry of Cytochalasans
77
However, there is no denying that cytochalasans offer novel mechanisms for exploitation in cancer therapy that may improve the efficacy of treatments against cancers
refractory to standard chemotherapeutic protocols. In the near future, it is possible
that cytochalasans could be used to supplement current chemotherapeutic measures
to improve efficacy rates, as well as to decrease the prevalence of drug resistance in
the clinical setting.
3.2 Antimicrobial Activities
In addition to their potential antineoplastic properties, cytochalasans also have been
found to possess considerable antimicrobial effects. The antimicrobial activities of
cytochalasins A (109) and D (2) were disclosed in the first report on the biological
characteristics of cytochalasans. Thus, cytochalasin A (109) was found to inhibit the
growth of Bacillus subtilis and Escherichia coli, as well as to exert antifungal activity
against Botrytis cinerea. In contrast, cytochalasin B (110) did not show any antifungal
activity against the test organisms and cytochalasin D (2) was only reported to have
antimycotic activity.
Moreover, other cytochalasans such as diaporthichalasin (192, phomopsichalasin), scoparasin B (205) and chaetoglobosins A (210) and C (212), isolated
from endophytic Chaetomium globosum, have been reported to have antimicrobial activity [223–225]. Diaporthichalasin (192, phomopsichalasin) isolated from a
culture of an endophytic Phomopsis species also has antimicrobial effects [90]; this
compound, in which the common macrocycle is replaced by a 13-membered tricyclic
system, showed antibacterial activity in disk diffusion assays against Bacillus subtilis,
Salmonella gallinarum and Staphylococcus aureus, as well as antifungal activity
against the yeast Candida tropicalis. Scoparasin B (205), a cytochalasin isolated
from the culture broth of the endophytic fungus Eutypella scoparia PSU-D44, was
reported have antifungal activity against the dermatophyte Microsporum gypseum
SH-MU-4 (MIC 30.3 μM) [101]. Chaetoglobosins A (210) and B (211), inhibited the
growth of Staphylococcus aureus, methicillin-resistant S. aureus, and Mycobacterium
tuberculosis H37Ra [226]. Further, Aouiche and coworkers reported that the MIC
values for chaetoglobosin A (210) were between 30 and 75 μg/cm
3 for yeasts, 50 and
75 μg/cm
3 for filamentous fungi, and 20 and 30 μg/cm
3 for Gram-positive bacteria
[13]. Also, several cytochalasans have shown significant inhibition of Staphylococcus
aureus biofilm formation at subtoxic levels, including cytochalasins A (109) and C
(1), chaetoglobosin A (210), 19,20-epoxycytochalasin C (52) and L-696,474 (26).
Among them, chaetoglobosin A was the most potent, as it inhibited 70–91% of
biofilm formation in Staphylococcus aureus [96].
Studies also provided insights into the mechanism of action and structure–activity
relationships of the antimicrobial activities of cytochalasans. For example, cytochalasin A (109) is a bacteriostatic agent that inhibits a variety of physiological processes
in Gram-positive bacteria, such as enzyme induction, transportation, and respiration
of exogenous substrates. The presence of an α,β-unsaturated carbonyl group in the
77
However, there is no denying that cytochalasans offer novel mechanisms for exploitation in cancer therapy that may improve the efficacy of treatments against cancers
refractory to standard chemotherapeutic protocols. In the near future, it is possible
that cytochalasans could be used to supplement current chemotherapeutic measures
to improve efficacy rates, as well as to decrease the prevalence of drug resistance in
the clinical setting.
3.2 Antimicrobial Activities
In addition to their potential antineoplastic properties, cytochalasans also have been
found to possess considerable antimicrobial effects. The antimicrobial activities of
cytochalasins A (109) and D (2) were disclosed in the first report on the biological
characteristics of cytochalasans. Thus, cytochalasin A (109) was found to inhibit the
growth of Bacillus subtilis and Escherichia coli, as well as to exert antifungal activity
against Botrytis cinerea. In contrast, cytochalasin B (110) did not show any antifungal
activity against the test organisms and cytochalasin D (2) was only reported to have
antimycotic activity.
Moreover, other cytochalasans such as diaporthichalasin (192, phomopsichalasin), scoparasin B (205) and chaetoglobosins A (210) and C (212), isolated
from endophytic Chaetomium globosum, have been reported to have antimicrobial activity [223–225]. Diaporthichalasin (192, phomopsichalasin) isolated from a
culture of an endophytic Phomopsis species also has antimicrobial effects [90]; this
compound, in which the common macrocycle is replaced by a 13-membered tricyclic
system, showed antibacterial activity in disk diffusion assays against Bacillus subtilis,
Salmonella gallinarum and Staphylococcus aureus, as well as antifungal activity
against the yeast Candida tropicalis. Scoparasin B (205), a cytochalasin isolated
from the culture broth of the endophytic fungus Eutypella scoparia PSU-D44, was
reported have antifungal activity against the dermatophyte Microsporum gypseum
SH-MU-4 (MIC 30.3 μM) [101]. Chaetoglobosins A (210) and B (211), inhibited the
growth of Staphylococcus aureus, methicillin-resistant S. aureus, and Mycobacterium
tuberculosis H37Ra [226]. Further, Aouiche and coworkers reported that the MIC
values for chaetoglobosin A (210) were between 30 and 75 μg/cm
3 for yeasts, 50 and
75 μg/cm
3 for filamentous fungi, and 20 and 30 μg/cm
3 for Gram-positive bacteria
[13]. Also, several cytochalasans have shown significant inhibition of Staphylococcus
aureus biofilm formation at subtoxic levels, including cytochalasins A (109) and C
(1), chaetoglobosin A (210), 19,20-epoxycytochalasin C (52) and L-696,474 (26).
Among them, chaetoglobosin A was the most potent, as it inhibited 70–91% of
biofilm formation in Staphylococcus aureus [96].
Studies also provided insights into the mechanism of action and structure–activity
relationships of the antimicrobial activities of cytochalasans. For example, cytochalasin A (109) is a bacteriostatic agent that inhibits a variety of physiological processes
in Gram-positive bacteria, such as enzyme induction, transportation, and respiration
of exogenous substrates. The presence of an α,β-unsaturated carbonyl group in the