136
J. Pospíšil et al.
administration of 41 (rat adenocarcinoma cells). Quercetin (41) also inhibited proliferation in case of non-small cell lung carcinoma cell lines and hepatoma cell growth
(ML-3 murine hepatoma cells) [179–181]. Tangeretin (50) (a methoxylated flavone)
and genistein (33) (an isoflavone) were shown to suppress the growth of HL-60 cells.
Genistein (33) and kaempferol (49, a widely studied flavonol) were found to inhibit
the proliferation of human colon cancer cells (Caco-2 and HT29) [182–185].
The potential protective effects of kaempferol (49) have been described further for
cardiovascular diseases, obesity, and inflammation. Based on mechanistic studies,
it was concluded that 49 may reduce adipose tissue accumulation and improve the
symptoms of diabetes and hyperlipidemia (in mice) [186–191]. It was demonstrated
that 49 can also mediate apoptosis in pancreatic cancer cells via inhibition of the
EGFR/p38 signaling pathway, and also upregulate p21 expression and downregulate
cyclin B1 expression in cancer cells, leading to apoptotic cell death [192–194].
The most prominent phenylpropanoid dimer with antineoplastic activity is
podophyllotoxin (51). This aryltetralin lignan may be extracted from Podophyllum
peltatum and was originally used medicinally in an ointment to treat genital warts
and molluscum contagiosum [195, 196]. Lignan 51 has the ability to bind to tubulin
and disrupt microtubule synthesis. Since this compound itself has severe secondary
toxic effects on the human body, structural modification was required to decrease its
toxicity while maintaining unchanged the original antiproliferative activity (see the
structures of etoposide (53) and teniposide (52), Fig. 9). These two epipodophyllotoxin glycoside derivatives (52 and 53) were approved by the U.S. FDA as novel
anticancer drugs for the treatment of various types of cancer (including Kaposi’s
sarcoma, certain lymphomas, lung cancer, and testicular cancer) [197]. The mode of
action of both etoposide (53) and teniposide (52) is based on their interaction with the
topoisomerase II enzyme, which prevents the religation of DNA strands [198–201].
Justicidin A (55) is structurally similar to podophyllotoxin and was isolated from
the plant Justicia procumbens L. (Acanthaceae). This plant is used in Chinese traditional medicine to treat fever, pain (via pharyngolaryngeal swelling), and also tumor
formation [202]. The mode of action of justicidin A (55) seems to be the same as
that of tuberculatin (54) and presumably activates tumor necrosis factor R [203].
3.3.4 Anti-inflammatory Activity
Inflammation is the basic response of the immune system to an irritant stimulus (e.g.,
from bacteria, viral or fungal pathogens, radiation, chemical damage, or wounding of
tissues). The external characteristics of inflammation include redness, heat, swelling,
pain, and loss of function, but not all of these symptoms are always present. During
this process, the immune system can identify both the damage made and the pathogen
responsible and to isolate these and promote healing. However, if the immune system
is not working properly, the wrong tissue can be attacked (repetitively) and undesired
(chronic) damage can take place [204].
Various phenolic compounds act to prevent such toxic effects (Fig. 10). In general,
they are able to restore the redox balance via interactions with ROS. Therefore, the
J. Pospíšil et al.
administration of 41 (rat adenocarcinoma cells). Quercetin (41) also inhibited proliferation in case of non-small cell lung carcinoma cell lines and hepatoma cell growth
(ML-3 murine hepatoma cells) [179–181]. Tangeretin (50) (a methoxylated flavone)
and genistein (33) (an isoflavone) were shown to suppress the growth of HL-60 cells.
Genistein (33) and kaempferol (49, a widely studied flavonol) were found to inhibit
the proliferation of human colon cancer cells (Caco-2 and HT29) [182–185].
The potential protective effects of kaempferol (49) have been described further for
cardiovascular diseases, obesity, and inflammation. Based on mechanistic studies,
it was concluded that 49 may reduce adipose tissue accumulation and improve the
symptoms of diabetes and hyperlipidemia (in mice) [186–191]. It was demonstrated
that 49 can also mediate apoptosis in pancreatic cancer cells via inhibition of the
EGFR/p38 signaling pathway, and also upregulate p21 expression and downregulate
cyclin B1 expression in cancer cells, leading to apoptotic cell death [192–194].
The most prominent phenylpropanoid dimer with antineoplastic activity is
podophyllotoxin (51). This aryltetralin lignan may be extracted from Podophyllum
peltatum and was originally used medicinally in an ointment to treat genital warts
and molluscum contagiosum [195, 196]. Lignan 51 has the ability to bind to tubulin
and disrupt microtubule synthesis. Since this compound itself has severe secondary
toxic effects on the human body, structural modification was required to decrease its
toxicity while maintaining unchanged the original antiproliferative activity (see the
structures of etoposide (53) and teniposide (52), Fig. 9). These two epipodophyllotoxin glycoside derivatives (52 and 53) were approved by the U.S. FDA as novel
anticancer drugs for the treatment of various types of cancer (including Kaposi’s
sarcoma, certain lymphomas, lung cancer, and testicular cancer) [197]. The mode of
action of both etoposide (53) and teniposide (52) is based on their interaction with the
topoisomerase II enzyme, which prevents the religation of DNA strands [198–201].
Justicidin A (55) is structurally similar to podophyllotoxin and was isolated from
the plant Justicia procumbens L. (Acanthaceae). This plant is used in Chinese traditional medicine to treat fever, pain (via pharyngolaryngeal swelling), and also tumor
formation [202]. The mode of action of justicidin A (55) seems to be the same as
that of tuberculatin (54) and presumably activates tumor necrosis factor R [203].
3.3.4 Anti-inflammatory Activity
Inflammation is the basic response of the immune system to an irritant stimulus (e.g.,
from bacteria, viral or fungal pathogens, radiation, chemical damage, or wounding of
tissues). The external characteristics of inflammation include redness, heat, swelling,
pain, and loss of function, but not all of these symptoms are always present. During
this process, the immune system can identify both the damage made and the pathogen
responsible and to isolate these and promote healing. However, if the immune system
is not working properly, the wrong tissue can be attacked (repetitively) and undesired
(chronic) damage can take place [204].
Various phenolic compounds act to prevent such toxic effects (Fig. 10). In general,
they are able to restore the redox balance via interactions with ROS. Therefore, the