China and Western Ghats of India (Pu et al. 2019). The herbaceous species of
Ophiorrhiza are mainly spread across the Western Ghats of India, particularly at
Travancore, Wynaad, Anamalai, and Kemmannugundi. Besides, these species
occur in the regions of Assam, Andamans and Nicobars islands, Srilanka, Thailand,
Philippines, Malaysia, and China (Namdeo et al. 2012; Kaushisk et al. 2015). The
organs of Ophiorrhiza species produce low levels of CPT content. Similarly,
CPT-yielding C. grandiflora (Apocynaceae), which is a latex-bearing shrubby
climber has been observed by Kulkarni et al. (2010), and this plant is prevalent in
the regions of Kerala and Karnataka in India. The content of CPT in these plants
ranges between 0.600 and 1.350%. In C. acuminata, CPT content ranges from
0.012 to 0.236%, while in N. nimmoniana, it ranges from 0.081 to 0.775%,
depending on different organs, and these plant species are the chief sources for CPT
extraction in large scale (Liu et al. 1998; Lorence and Nessler 2004; Ramesha et al.
2008; Khan et al. 2013; Isah and Mujib 2015). In C. acuminata, the accretion of
CPT largely depends on branch, age of the tree, and seasons. Moreover, the
increased shade enhances CPT accumulation (Liu et al. 1998). It was established by
a study that N. nimmoniana inner root bark and stem bark contained with the CPT
amount of 0.23 and 0.33%, respectively (Uma et al. 2008; Isah and Mujib 2015).
9.3.2 Camptothecin from Endophytes
The plant-derived CPT cannot meet the global demand, and hence constant efforts
are being carried out to recognize novel alternative resources of CPT. In this regard,
endophytic microbes can be a choice for obtaining CPT (Uzma et al. 2018). There
are limited reports on the CPT-yielding endophytic microorganisms that were
identified, associated with CPT-producing plants. In a study, an endophytic fungus
(Entrophospora infrequens) was isolated from N. foetida, growing in the coastal
regions of India (Puri et al. 2005). The endophytic fungus was cultured in
Sabouraud broth, a synthetic liquid media having dextrose (4%) and peptone (1%)
under shaking conditions. Cultures, producing CPT was identified using both
chromatographic and spectral evaluations. Further, they reported that CPT obtained
from fungal cultures with anticancer activity against cancer cells, namely A-549 (a
lung cancer), HEP-2 (a liver), and OVCAR-5 (ovarian) cancer cell lines. They
testified the sequestration of about 18 lg/mg CPT content from the E. infrequens
chloroform extract. Likewise, another study by Amna et al. (2006), used a bioreactor for culturing E. infrequens, and they found the synthesis of high levels of CPT
(4.96 mg/100 g of dry mass) after 48 h. The optimum conditions, i.e., pH of 5.6,
temperature of 28 ± 2 °C, agitation rate of 200–230 rpm, and aeration rate of 1
vvm were found optimal for the growth of E. infrequens in bioreactor culture, and
to produce higher levels of CPT. The above studies clearly suggest the possible use
of E. infrequens endophyte to produce CPT on a large-scale by employing
bioreactors.
9 Camptothecin: Occurrence, Chemistry and Mode of Action
317
Ophiorrhiza are mainly spread across the Western Ghats of India, particularly at
Travancore, Wynaad, Anamalai, and Kemmannugundi. Besides, these species
occur in the regions of Assam, Andamans and Nicobars islands, Srilanka, Thailand,
Philippines, Malaysia, and China (Namdeo et al. 2012; Kaushisk et al. 2015). The
organs of Ophiorrhiza species produce low levels of CPT content. Similarly,
CPT-yielding C. grandiflora (Apocynaceae), which is a latex-bearing shrubby
climber has been observed by Kulkarni et al. (2010), and this plant is prevalent in
the regions of Kerala and Karnataka in India. The content of CPT in these plants
ranges between 0.600 and 1.350%. In C. acuminata, CPT content ranges from
0.012 to 0.236%, while in N. nimmoniana, it ranges from 0.081 to 0.775%,
depending on different organs, and these plant species are the chief sources for CPT
extraction in large scale (Liu et al. 1998; Lorence and Nessler 2004; Ramesha et al.
2008; Khan et al. 2013; Isah and Mujib 2015). In C. acuminata, the accretion of
CPT largely depends on branch, age of the tree, and seasons. Moreover, the
increased shade enhances CPT accumulation (Liu et al. 1998). It was established by
a study that N. nimmoniana inner root bark and stem bark contained with the CPT
amount of 0.23 and 0.33%, respectively (Uma et al. 2008; Isah and Mujib 2015).
9.3.2 Camptothecin from Endophytes
The plant-derived CPT cannot meet the global demand, and hence constant efforts
are being carried out to recognize novel alternative resources of CPT. In this regard,
endophytic microbes can be a choice for obtaining CPT (Uzma et al. 2018). There
are limited reports on the CPT-yielding endophytic microorganisms that were
identified, associated with CPT-producing plants. In a study, an endophytic fungus
(Entrophospora infrequens) was isolated from N. foetida, growing in the coastal
regions of India (Puri et al. 2005). The endophytic fungus was cultured in
Sabouraud broth, a synthetic liquid media having dextrose (4%) and peptone (1%)
under shaking conditions. Cultures, producing CPT was identified using both
chromatographic and spectral evaluations. Further, they reported that CPT obtained
from fungal cultures with anticancer activity against cancer cells, namely A-549 (a
lung cancer), HEP-2 (a liver), and OVCAR-5 (ovarian) cancer cell lines. They
testified the sequestration of about 18 lg/mg CPT content from the E. infrequens
chloroform extract. Likewise, another study by Amna et al. (2006), used a bioreactor for culturing E. infrequens, and they found the synthesis of high levels of CPT
(4.96 mg/100 g of dry mass) after 48 h. The optimum conditions, i.e., pH of 5.6,
temperature of 28 ± 2 °C, agitation rate of 200–230 rpm, and aeration rate of 1
vvm were found optimal for the growth of E. infrequens in bioreactor culture, and
to produce higher levels of CPT. The above studies clearly suggest the possible use
of E. infrequens endophyte to produce CPT on a large-scale by employing
bioreactors.
9 Camptothecin: Occurrence, Chemistry and Mode of Action
317