Recent Advances in the Chemistry and Pharmacology of Cryptolepine
201
alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in
B16 melanoma cells. Biochemistry 37:5136
42. Lisgarten JN, Coll M, Portugal J, Wright CW, Aymami J (2002) The antimalarial and cytotoxic
drug cryptolepine intercalates into DNA at cytosine-cytosine sites. Nat Struct Biol 9:57
43. Forkuo AD, Ansah C, Mensah KB, Annan K, Gyan, B, Theron A Mancama D, Wright CW
(2017) In vitro antimalarial interaction and gametocytocidal activity of cryptolepine. Malaria
J 16:496
44. Wells TNC, Alonso PL, Gutteridge WE (2009) New medicines to improve control and
contribute to the eradication of malaria. Nat Rev Drug Discov 8:879
45. Forkuo AD, Ansah C, Boadu KM, Boampong JN, Ameyaw EO, Gyan BA, Arku AT, Ofori MF
(2016) Synergistic anti-malarial action of cryptolepine and artemisinins. Malaria J 15:89
46. Ameyaw EO, Asmah KB, Biney RP, Henneh IT, Owusu-Agyei P, Prah J, Forkuo AD
2018. Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug
candidates, cryptolepine and xylopic acid, in Plasmodium berghei infected mice. Malaria J
17:153/1
47. Lavrado J, Cabal GG, Prudêncio M, Mota MM, Gut J, Rosenthal PJ, Diaz C, Guedes RC,
dos Santos DJVA, Bichenkova E, Douglas KT, Moreira R, Paulo A (2011) Incorporation of
basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and
mechanistic studies. J Med Chem 54:734
48. Lavrado J, Paulo A, Bichenkova E, Douglas KT, Moreira R (2012) 1 H NMR spectroscopic
identification of protonable sites in cryptolepines with C-11 substituents containing two amino
functionalities. Mag Reson Chem 50:216
49. Behzadi H, Olai MRTB, van der Spoel D (2011) Probing 13 C chemical shielding tensors in
cryptolepine and two bromo-substituted analogs for antiplasmodial activity. J Mol Mod 17:3289
50. Mududdla R, Mohankrishnan D, Bharate SS, Vishwakarma RA, Sahal D, Bharate SB (2018)
Orally effective aminoalkyl 10H-indolo[3,2-b]quinoline-11-carboxamide kills the malaria
parasite by inhibiting host haemoglobin uptake. ChemMedChem 13:2581
51. Abacha YZ (2020) Investigation of Nigerian ethnomedicinal plants as potential sources of
cytotoxic and antiplasmodial compounds. PhD thesis, University of Bradford, Bradford, UK,
p 165
52. Oluwafemi AJ, Okanla EO, Camps P, Muñoz-Torrero D, Mackey ZB, Chiang PK, Seville S,
Wright CW (2009) Evaluation of cryptolepine and huperzine derivatives as lead compounds
towards new agents for the treatment of human African trypanosomiasis. Nat Prod Commun
4:193
53. Arguelles AJ, Cordell GA, Maruenda H (2016) Molecular docking and binding mode analysis of
plant alkaloids as in vitro and in silico inhibitors of trypanothione reductase from Trypanosoma
cruzi. Nat Prod Commun 11:57
54. Lavrado J, Mackey Z, Hansell E, McKerrow JH, Paulo A, Moreira R (2012) Antitrypanosomal
and cysteine protease inhibitory activities of alkyldiamine cryptolepine derivatives. Bioorg
Med Chem Lett 22:6256
55. Belaidi S, Salah T, Ndjib M, Sinha L, Prasad O (2015) Structure activity relationships modeling
of antitrypanosomal activities of alkyldiamine derivatives. J Comput Theor Nanosci 12:2421
56. Pal HC, Prasad R, Katiyar SK (2017) Cryptolepine inhibits melanoma cell growth through
coordinated changes in mitochondrial biogenesis, dynamics and metabolic tumor suppressor
AMPKα1/2-LKB1. Sci Rep 7:1498
57. Yuan JM, Wei K, Zhang GH, Chen NY, Wei XW, Pan CX, Mo DL, Su GF (2019) Cryptolepine
and aromathecin based mimics as potent G-quadruplex-binding, DNA-cleavage and anticancer
agents: Design, synthesis and DNA targeting-induced apoptosis. Eur J Med Chem 169:144
58. Qin QP, Wei ZZ, Wang ZF, Huang XL, Tan MX, Zou HH, Liang H (2020) Imaging and
therapeutic applications of Zn(II)-cryptolepine-curcumin molecular probes in cell apoptosis
detection and photodynamic therapy. Chem Commun 56:3999
59. Laryea D, Isaksson A, Wright CW, Larsson R, Nygren P (2009) Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumor cell lines and primary
cultures of tumor cells from patients. Invest New Drugs 27:402
201
alkaloid cryptolepine interferes with topoisomerase II and inhibits primarily DNA synthesis in
B16 melanoma cells. Biochemistry 37:5136
42. Lisgarten JN, Coll M, Portugal J, Wright CW, Aymami J (2002) The antimalarial and cytotoxic
drug cryptolepine intercalates into DNA at cytosine-cytosine sites. Nat Struct Biol 9:57
43. Forkuo AD, Ansah C, Mensah KB, Annan K, Gyan, B, Theron A Mancama D, Wright CW
(2017) In vitro antimalarial interaction and gametocytocidal activity of cryptolepine. Malaria
J 16:496
44. Wells TNC, Alonso PL, Gutteridge WE (2009) New medicines to improve control and
contribute to the eradication of malaria. Nat Rev Drug Discov 8:879
45. Forkuo AD, Ansah C, Boadu KM, Boampong JN, Ameyaw EO, Gyan BA, Arku AT, Ofori MF
(2016) Synergistic anti-malarial action of cryptolepine and artemisinins. Malaria J 15:89
46. Ameyaw EO, Asmah KB, Biney RP, Henneh IT, Owusu-Agyei P, Prah J, Forkuo AD
2018. Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug
candidates, cryptolepine and xylopic acid, in Plasmodium berghei infected mice. Malaria J
17:153/1
47. Lavrado J, Cabal GG, Prudêncio M, Mota MM, Gut J, Rosenthal PJ, Diaz C, Guedes RC,
dos Santos DJVA, Bichenkova E, Douglas KT, Moreira R, Paulo A (2011) Incorporation of
basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and
mechanistic studies. J Med Chem 54:734
48. Lavrado J, Paulo A, Bichenkova E, Douglas KT, Moreira R (2012) 1 H NMR spectroscopic
identification of protonable sites in cryptolepines with C-11 substituents containing two amino
functionalities. Mag Reson Chem 50:216
49. Behzadi H, Olai MRTB, van der Spoel D (2011) Probing 13 C chemical shielding tensors in
cryptolepine and two bromo-substituted analogs for antiplasmodial activity. J Mol Mod 17:3289
50. Mududdla R, Mohankrishnan D, Bharate SS, Vishwakarma RA, Sahal D, Bharate SB (2018)
Orally effective aminoalkyl 10H-indolo[3,2-b]quinoline-11-carboxamide kills the malaria
parasite by inhibiting host haemoglobin uptake. ChemMedChem 13:2581
51. Abacha YZ (2020) Investigation of Nigerian ethnomedicinal plants as potential sources of
cytotoxic and antiplasmodial compounds. PhD thesis, University of Bradford, Bradford, UK,
p 165
52. Oluwafemi AJ, Okanla EO, Camps P, Muñoz-Torrero D, Mackey ZB, Chiang PK, Seville S,
Wright CW (2009) Evaluation of cryptolepine and huperzine derivatives as lead compounds
towards new agents for the treatment of human African trypanosomiasis. Nat Prod Commun
4:193
53. Arguelles AJ, Cordell GA, Maruenda H (2016) Molecular docking and binding mode analysis of
plant alkaloids as in vitro and in silico inhibitors of trypanothione reductase from Trypanosoma
cruzi. Nat Prod Commun 11:57
54. Lavrado J, Mackey Z, Hansell E, McKerrow JH, Paulo A, Moreira R (2012) Antitrypanosomal
and cysteine protease inhibitory activities of alkyldiamine cryptolepine derivatives. Bioorg
Med Chem Lett 22:6256
55. Belaidi S, Salah T, Ndjib M, Sinha L, Prasad O (2015) Structure activity relationships modeling
of antitrypanosomal activities of alkyldiamine derivatives. J Comput Theor Nanosci 12:2421
56. Pal HC, Prasad R, Katiyar SK (2017) Cryptolepine inhibits melanoma cell growth through
coordinated changes in mitochondrial biogenesis, dynamics and metabolic tumor suppressor
AMPKα1/2-LKB1. Sci Rep 7:1498
57. Yuan JM, Wei K, Zhang GH, Chen NY, Wei XW, Pan CX, Mo DL, Su GF (2019) Cryptolepine
and aromathecin based mimics as potent G-quadruplex-binding, DNA-cleavage and anticancer
agents: Design, synthesis and DNA targeting-induced apoptosis. Eur J Med Chem 169:144
58. Qin QP, Wei ZZ, Wang ZF, Huang XL, Tan MX, Zou HH, Liang H (2020) Imaging and
therapeutic applications of Zn(II)-cryptolepine-curcumin molecular probes in cell apoptosis
detection and photodynamic therapy. Chem Commun 56:3999
59. Laryea D, Isaksson A, Wright CW, Larsson R, Nygren P (2009) Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumor cell lines and primary
cultures of tumor cells from patients. Invest New Drugs 27:402