198
S. D. Shnyder and C. W. Wright
Interestingly, none of the compounds caused significant DNA damage to human
sperm at 300 μM.
In ex vivo studies in zebrafish (Danio rerio) embryos, Mensah et al. [77] demonstrated for the first time that treatment with 1 induced significant developmental
malformations, along with growth retardation and mortality at 100 μM, but not
at lower concentrations [77]. Malformations in the eleutheroembryos included a
decrease in eye diameter and protuberance, signs of muscular atrophy, increased
edema in the yolk sac, and enlargement of the pericardial area with a resultant
decrease in heart rate. Overall, these studies suggest that 1 and its analogs may
be potentially genotoxic, although the risks to humans are uncertain.
11 Miscellaneous Studies
Work aimed at understanding the fluorescence properties of 1 and analogs has been
carried out by Mariz et al. [78], and recently the photophysics of 1 in the presence
of the macrocyclic host cucurbit [7] uril and DNA has been explored [79].
12 Conclusion
This contribution has documented that the plant alkaloid cryptolepine (1) and its
analogs continue to be of interest to researchers, especially as leads toward new
therapeutic agents for the treatment of protozoal diseases and cancer. The research
discussed has been facilitated by the development of several new approaches to the
synthesis of analogs of 1 as well as advances in the understanding of the mechanisms
by which 1 exerts its pharmacological effects. 2,7-Dibromocryptoleptine (43) has
been shown to be a lead compound toward novel antimalarial and antitrypanosomal
drugs, while several analogs of 1 have been reported to have potentially interesting
in vivo antineoplastic activity. Challenges for future work include the development
of further derivatives that have good bioavailability, low toxicity, and are affordable.
References
1. Wright CW (2008) Cryptolepine. In: Hawthorne S (ed) Natural products as future medicinal
agents. Transworld Research Network, Kerala, India, p 117
2. The Plant List (2020) http://www.theplantlist.org/
3. Chatterjee A, Kumar S, Chattopadhyay SK (2013) A validated HPLC-PDA method for identification of two bioactive alkaloids, ephedrine and cryptolepine, in different Sida species. Biomed
Chromatogr 27:1720
S. D. Shnyder and C. W. Wright
Interestingly, none of the compounds caused significant DNA damage to human
sperm at 300 μM.
In ex vivo studies in zebrafish (Danio rerio) embryos, Mensah et al. [77] demonstrated for the first time that treatment with 1 induced significant developmental
malformations, along with growth retardation and mortality at 100 μM, but not
at lower concentrations [77]. Malformations in the eleutheroembryos included a
decrease in eye diameter and protuberance, signs of muscular atrophy, increased
edema in the yolk sac, and enlargement of the pericardial area with a resultant
decrease in heart rate. Overall, these studies suggest that 1 and its analogs may
be potentially genotoxic, although the risks to humans are uncertain.
11 Miscellaneous Studies
Work aimed at understanding the fluorescence properties of 1 and analogs has been
carried out by Mariz et al. [78], and recently the photophysics of 1 in the presence
of the macrocyclic host cucurbit [7] uril and DNA has been explored [79].
12 Conclusion
This contribution has documented that the plant alkaloid cryptolepine (1) and its
analogs continue to be of interest to researchers, especially as leads toward new
therapeutic agents for the treatment of protozoal diseases and cancer. The research
discussed has been facilitated by the development of several new approaches to the
synthesis of analogs of 1 as well as advances in the understanding of the mechanisms
by which 1 exerts its pharmacological effects. 2,7-Dibromocryptoleptine (43) has
been shown to be a lead compound toward novel antimalarial and antitrypanosomal
drugs, while several analogs of 1 have been reported to have potentially interesting
in vivo antineoplastic activity. Challenges for future work include the development
of further derivatives that have good bioavailability, low toxicity, and are affordable.
References
1. Wright CW (2008) Cryptolepine. In: Hawthorne S (ed) Natural products as future medicinal
agents. Transworld Research Network, Kerala, India, p 117
2. The Plant List (2020) http://www.theplantlist.org/
3. Chatterjee A, Kumar S, Chattopadhyay SK (2013) A validated HPLC-PDA method for identification of two bioactive alkaloids, ephedrine and cryptolepine, in different Sida species. Biomed
Chromatogr 27:1720