Progress in the Chemistry of Cytochalasans
79
3.4 Anti-inflammatory Effects
The anti-inflammatory effects of cytochalasans also have been reported. Chaetoglobosin Fex (227), isolated from the marine-derived endophytic fungus Chaetomium
globosum QEN-14, inhibited significant LPS-induced inflammatory mediator
production both in the RAW264.7 cell line and in mouse peritoneal macrophages. Its
anti-inflammatory property was explained by inhibiting NF-κB and MAPKs activation in LPS-stimulated macrophages, and by blocking membrane-associated CD14
(mCD14) expression [231]. Compound 227 also exhibited an immunosuppressive
effect on mouse bone marrow-derived DCs (BMDCs) via TLR3 signaling, which
suggested its potential application in the treatment of autoimmune inflammatory
diseases [232]. Chaetoglobosin F (215), obtained from an EtOAc extract of a solid
culture of Chaetomium globosum IFB-E019, also showed anti-inflammatory effects
on BMDCs. Compound 215 inhibited the CpG-induced DC maturation and function
by suppressing the expression of surface molecules (CD40, CD80, CD86 and MHCII), reducing the production of cytokines and chemokines (IL-12 and CXCL-10),
inhibiting CpG-induced DCs-elicited allogeneic T-cell proliferation, and impairing
the migration ability of chemokines. Additionally, compound 215 inhibited CpGinduced-activation of MAPKs (p38 and JNK, but not ERK) and the nuclear translocation of NF-κB and STAT1. Furthermore, 215 was able to suppress TLR9 expression
of CpG-induced DCs. Collectively, these immunosuppressive properties of 215 may
prove useful in controlling DC-associated autoimmune and/or inflammatory diseases
[233].
3.5 Antiviral Activities
The antiviral activities of cytochalasin derivatives also have been reported. Thus,
HIV-1 protease plays a crucial role in viral maturation: its inhibition results in the
reduced spread of infectious viruses. Goetz and coworkers isolated a novel cytochalasin L-696,474 (26), and found it to be a competitive inhibitor of HIV-1 protease
that did not possess any apparent cytotoxicity [14]. In 2004, 19,20-epoxycytochalasin
Q Edwards (31) was found to be an antagonist of the chemokine receptor CCR5,
which is implicated in HIV infection [234]. Aspochalasin L (354), isolated from a
fermentation broth of Aspergillus flavipes, has been reported with activity against
HIV integrase, with an IC 50 of 71.7 μM [165]. Che and coworkers reported that
alachalasin A (471), with an unusual adenine substituent isolated from Podospora
vesticola, displayed an inhibitory effect on HIV-1 replication in C8166 cells [12].
In 2015, Zhang and coworkers reported that armochaetoglobins L (302), M (303),
N (304), Q (307), R (308), and penochalasin B (298), as isolated from a culture
broth of Chaetomium globosum TW1-1, showed significant anti-HIV activities, with
EC 50 values ranging from 0.11 to 0.55 μM [144]. These results suggest that certain
cytochalasans could be of interest for development as anti-HIV agents. However,
79
3.4 Anti-inflammatory Effects
The anti-inflammatory effects of cytochalasans also have been reported. Chaetoglobosin Fex (227), isolated from the marine-derived endophytic fungus Chaetomium
globosum QEN-14, inhibited significant LPS-induced inflammatory mediator
production both in the RAW264.7 cell line and in mouse peritoneal macrophages. Its
anti-inflammatory property was explained by inhibiting NF-κB and MAPKs activation in LPS-stimulated macrophages, and by blocking membrane-associated CD14
(mCD14) expression [231]. Compound 227 also exhibited an immunosuppressive
effect on mouse bone marrow-derived DCs (BMDCs) via TLR3 signaling, which
suggested its potential application in the treatment of autoimmune inflammatory
diseases [232]. Chaetoglobosin F (215), obtained from an EtOAc extract of a solid
culture of Chaetomium globosum IFB-E019, also showed anti-inflammatory effects
on BMDCs. Compound 215 inhibited the CpG-induced DC maturation and function
by suppressing the expression of surface molecules (CD40, CD80, CD86 and MHCII), reducing the production of cytokines and chemokines (IL-12 and CXCL-10),
inhibiting CpG-induced DCs-elicited allogeneic T-cell proliferation, and impairing
the migration ability of chemokines. Additionally, compound 215 inhibited CpGinduced-activation of MAPKs (p38 and JNK, but not ERK) and the nuclear translocation of NF-κB and STAT1. Furthermore, 215 was able to suppress TLR9 expression
of CpG-induced DCs. Collectively, these immunosuppressive properties of 215 may
prove useful in controlling DC-associated autoimmune and/or inflammatory diseases
[233].
3.5 Antiviral Activities
The antiviral activities of cytochalasin derivatives also have been reported. Thus,
HIV-1 protease plays a crucial role in viral maturation: its inhibition results in the
reduced spread of infectious viruses. Goetz and coworkers isolated a novel cytochalasin L-696,474 (26), and found it to be a competitive inhibitor of HIV-1 protease
that did not possess any apparent cytotoxicity [14]. In 2004, 19,20-epoxycytochalasin
Q Edwards (31) was found to be an antagonist of the chemokine receptor CCR5,
which is implicated in HIV infection [234]. Aspochalasin L (354), isolated from a
fermentation broth of Aspergillus flavipes, has been reported with activity against
HIV integrase, with an IC 50 of 71.7 μM [165]. Che and coworkers reported that
alachalasin A (471), with an unusual adenine substituent isolated from Podospora
vesticola, displayed an inhibitory effect on HIV-1 replication in C8166 cells [12].
In 2015, Zhang and coworkers reported that armochaetoglobins L (302), M (303),
N (304), Q (307), R (308), and penochalasin B (298), as isolated from a culture
broth of Chaetomium globosum TW1-1, showed significant anti-HIV activities, with
EC 50 values ranging from 0.11 to 0.55 μM [144]. These results suggest that certain
cytochalasans could be of interest for development as anti-HIV agents. However,