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Current Analytical Chemistry

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ISSN (Print): 1573-4110
ISSN (Online): 1875-6727

Research Article

Camptothecin and its Analogs: High-Yielding Ophiorrhiza Species from Sri Lanka for Sustainable Anticancer Compound Production

Author(s): Hewagamage Dona Gihani Asmeer Ranasinghe, Peramune Arachchilage Amila Saman Prasad Kumara, Koonara Mudiyanselage Thilini Dinesha Weerasekara, Poruthotage Pradeep Rasika Perera, Nazeera Salim and Chandrika Udumalagala Gamage*

Volume 20, Issue 8, 2024

Published on: 02 May, 2024

Page: [599 - 610] Pages: 12

DOI: 10.2174/0115734110285332240424093539

Price: $65

Abstract

Introduction: Camptothecin (CPT) is pivotal in cancer treatment, derived from various CPT-producing plant species, and is a fundamental component in synthesizing valuable cancer drugs like Irinotecan and Topotecan. Sourcing from nature poses conservation issues, fostering interest in the herbaceous Ophiorrhiza plant as a more sustainable alternative. Ophiorrhiza species in Sri Lanka lack comprehensive study, warranting exploration for echo-friendly anticancer compound production.

Objectives: This study examines CPT and analog content in Ophiorrhiza mungos, O. pectinata, and O. rugosa across diverse Sri Lankan regions.

Methods: The study employs Thin Layer Chromatography (TLC), High-Performance Liquid Chromatography- DAD (HPLC-DAD), and Liquid Chromatography-Mass Spectrometry (LC-MS) to quantify and confirm CPT and its analogs.

Results: Significant variations in the content of CPT and its analogs were observed among plant parts and regions. O. mungos from Deraniyagala and Bibile regions notably exhibited elevated CPT levels in fruits and roots. O. rugosa var. Angustifolia and O. pectinata also exhibited a considerable content of CPT in their roots, though it was significantly lower (p < 0.005) than O. mungos.

Conclusion: The study validates analytical methods for specificity, linearity, precision, accuracy, and sensitivity per ICH guidelines. The results indicate that Ophiorrhiza species, especially O. mungos and O. rugosa var. Angustifolia holds the potential to be a sustainable source of CPT. Optimizing cultivation practices offers an eco-friendly solution for anticancer compound production, alleviating species threats and conserving biodiversity.

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[1]
Hsiang, Y.H.; Hertzberg, R.; Hecht, S.; Liu, L.F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J. Biol. Chem., 1985, 260(27), 14873-14878.
[http://dx.doi.org/10.1016/S0021-9258(17)38654-4] [PMID: 2997227]
[2]
Wall, M.E.; Wani, M.C.; Cook, C.E.; Palmer, K.H.; McPhail, A.T.; Sim, G.A. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata1,2. J. Am. Chem. Soc., 1966, 88(16), 3888-3890.
[http://dx.doi.org/10.1021/ja00968a057]
[3]
Govindachari, T.R.; Viswanathan, N. Alkaloids of Mappia foetida. Phytochemistry, 1972, 11(12), 3529-3531.
[http://dx.doi.org/10.1016/S0031-9422(00)89852-0]
[4]
Degambada, K.D.; Arachchilage, P.A.S.P.K.; Salim, N.; Chandrika, U.G.; Abeysekera, A.M. Cellular localisation and quantification of Camptothecin in different plant parts of Nothapodytes nimmoniana (J. Graham) Mabberley of Sri Lankan origin. Phytochem. Anal., 2023, 34(4), 453-460.
[http://dx.doi.org/10.1002/pca.3226] [PMID: 37015831]
[5]
Malpathak, N.P.; Kulkarni, A.V.; Patwardhan, A.A.; Lele, U. Production of camptothecin in cultures of Chonemorpha grandiflora. Pharmacognosy Res., 2010, 2(5), 296-299.
[http://dx.doi.org/10.4103/0976-4836.72327] [PMID: 21589755]
[6]
Gunasekera, S.P.; Badawi, M.M.; Cordell, G.A.; Farnsworth, N.R.; Chitnis, M. Plant anticancer agents X. Isolation of camptothecin and 9-methoxycamptothecin from Ervatamia heyneana. J. Nat. Prod., 1979, 42(5), 475-477.
[http://dx.doi.org/10.1021/np50005a006] [PMID: 521817]
[7]
Arisawa, M.; Gunasekera, S.; Cordell, G.; Farnsworth, N. Plant anticancer agents XXI. Constituents of Merrilliodendron megacarpum. Planta Med., 1981, 43(12), 404-407.
[http://dx.doi.org/10.1055/s-2007-971533] [PMID: 7330109]
[8]
Zhou, B.N.; Hoch, J.M.; Johnson, R.K.; Mattern, M.R.; Eng, W.K.; Ma, J.; Hecht, S.M.; Newman, D.J.; Kingston, D.G.I. Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source. J. Nat. Prod., 2000, 63(9), 1273-1276.
[http://dx.doi.org/10.1021/np000058r] [PMID: 11000035]
[9]
Arbain, D.; Putra, D.P.; Sargent, M.V. The alkaloids of Ophiorrhiza filistipula. Aust. J. Chem., 1993, 46(7), 977-985.
[http://dx.doi.org/10.1071/CH9930977]
[10]
Gharpure, G.; Chavan, B.; Lele, U.; Hastak, A.; Bhave, A.; Malpure, N.; Vasudeva, R.; Patwardhan, A. Camptothecin accumulation in ophiorrhiza rugosa var. prostrata from northern western ghats. Curr. Sci., 2010, 98(3), 302-304.
[11]
Tafur, S.; Nelson, J.D.; DeLong, D.C.; Svoboda, G.H. Antiviral components of Ophiorrhiza mungos. Isolation of camptothecin and 10-methoxycamptothecin. Lloydia, 1976, 39(4), 261-262.
[PMID: 957920]
[12]
Yamazaki, Y.; Urano, A.; Sudo, H.; Kitajima, M.; Takayama, H.; Yamazaki, M.; Aimi, N.; Saito, K. Metabolite profiling of alkaloids and strictosidine synthase activity in camptothecin producing plants. Phytochemistry, 2003, 62(3), 461-470.
[http://dx.doi.org/10.1016/S0031-9422(02)00543-5] [PMID: 12620359]
[13]
Liu, Y.Q.; Li, W.Q.; Morris-Natschke, S.L.; Qian, K.; Yang, L.; Zhu, G.X.; Wu, X.B.; Chen, A.L.; Zhang, S.Y.; Nan, X.; Lee, K.H. Perspectives on biologically active camptothecin derivatives. Med. Res. Rev., 2015, 35(4), 753-789.
[http://dx.doi.org/10.1002/med.21342] [PMID: 25808858]
[14]
Lorence, A.; Nessler, C.L. Camptothecin, over four decades of surprising findings. Phytochemistry, 2004, 65(20), 2735-2749.
[http://dx.doi.org/10.1016/j.phytochem.2004.09.001] [PMID: 15474560]
[15]
Deepthi, S.; Satheeshkumar, K. Enhanced camptothecin production induced by elicitors in the cell suspension cultures of Ophiorrhiza mungos Linn. Plant Cell Tissue Organ Cult., 2016, 124(3), 483-493.
[http://dx.doi.org/10.1007/s11240-015-0908-y]
[16]
Thomas, S.Y.D.; Surminski, S.K.; Lieberei, R. Plant regeneration via somatic embryogenesis of Camptotheca acuminata in temporary immersion system (TIS). Plant Cell Tissue Organ Cult., 2008, 95(2), 163-173.
[http://dx.doi.org/10.1007/s11240-008-9428-3]
[17]
Sirikantaramas, S.; Yamazaki, M.; Saito, K. Camptothecin: Biosynthesis, biotechnological production and resistance mechanism. Adv. Botan. Res., 2013, 68, 139-161.
[18]
Pai, S.; Pawar, N.; Nimbalkar, M.; Kshirsagar, P.; Kolar, F.; Dixit, G. Seasonal variation in content of camptothecin from the bark of Nothapodytes nimmoniana (Grah.) Mabb., using HPLC analysis. Pharmacognosy Res., 2013, 5(3), 219-223.
[http://dx.doi.org/10.4103/0974-8490.112434] [PMID: 23901218]
[19]
Patwardhan, S.C.; Manuja, S.; Narasimhan, S.; Shah, S.L. From data to diagnosis and control using generalized orthonormal basis filters. Part II: Model predictive and fault tolerant control. J. Process Contr., 2006, 16(2), 157-175.
[http://dx.doi.org/10.1016/j.jprocont.2005.04.011]
[20]
Mandal, A.K.; Cyriac, K.S.; Upreti, R.P. Therapeutic aspects of Nothapodytes nimmoniana-A review. Int. J. Res. Anal. Rev, 2018, 5(4), 568-571.
[21]
Khan, I.A.; Aziz, A.; Munawar, S.H.; Munzoor, Z. Antiemetic activity of methanolic leaf extract of Rumex vesicarius Linn. Int. J. Pharm. Res. Allied Sci, 2013, 2(4), 33-37.
[22]
Namdeo, A.G.; Sharma, A. HPLC analysis of camptothecin content in various parts of Nothapodytes foetida collected on different periods. Asian Pac. J. Trop. Biomed., 2012, 2(5), 389-393.
[http://dx.doi.org/10.1016/S2221-1691(12)60062-8] [PMID: 23569936]
[23]
Asano, T.; Watase, I.; Sudo, H.; Kitajima, M.; Takayama, H.; Aimi, N.; Yamazaki, M.; Saito, K. Camptothecin production by in Vitro cultures of Ophiorrhiza liukiuensis and O. kuroiwai. Plant Biotechnol., 2004, 21(4), 275-281.
[http://dx.doi.org/10.5511/plantbiotechnology.21.275]
[24]
Jisha, K. A study on the production of Camptothecin from Ophiorrhiza Mungos and Nothapodytes Foetida using cell and tissue culture. PhD thesis, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, 2006.
[25]
Rehman, S.; Shawl, A.S.; Kour, A.; Andrabi, R.; Sudan, P.; Sultan, P.; Verma, V.; Qazi, G.N. An endophytic Neurospora sp. from Nothapodytes foetida producing camptothecin. Appl. Biochem. Microbiol., 2008, 44(2), 203-209.
[http://dx.doi.org/10.1134/S0003683808020130] [PMID: 18669267]
[26]
Shweta, S.; Bindu, J.H.; Raghu, J.; Suma, H.K.; Manjunatha, B.L.; Kumara, P.M.; Ravikanth, G.; Nataraja, K.N.; Ganeshaiah, K.N.; Uma Shaanker, R. Isolation of endophytic bacteria producing the anti-cancer alkaloid camptothecine from Miquelia dentata Bedd. (Icacinaceae). Phytomedicine, 2013, 20(10), 913-917.
[http://dx.doi.org/10.1016/j.phymed.2013.04.004] [PMID: 23694750]
[27]
Musavi, S.F.; Dhavale, A.; Balakrishnan, R.M. Optimization and kinetic modeling of cell-associated camptothecin production from an endophytic Fusarium oxysporum NFX06. Prep. Biochem. Biotechnol., 2015, 45(2), 158-172.
[http://dx.doi.org/10.1080/10826068.2014.907177] [PMID: 24840354]
[28]
Degambada, K.D.; Kumara, P.A.A.S.P.; Salim, N.; Abeysekera, A.M.; Chandrika, U.G. Diaporthe sp. F18; A new source of camptothecin-producing endophytic fungus from Nothapodytes nimmoniana growing in Sri Lanka. Nat. Prod. Res., 2021, 37(1), 113-118.
[PMID: 34212791]
[29]
Rajan, R.; Varghese, S.C.; Kurup, R.; Gopalakrishnan, R.; Venkataraman, R.; Satheeshkumar, K.; Baby, S. Search for camptothecin-yielding Ophiorrhiza species from southern western ghats in India: A HPTLC-densitometry study. Ind. Crops Prod., 2013, 43, 472-476.
[http://dx.doi.org/10.1016/j.indcrop.2012.07.054]
[30]
Bremer, B.; Manen, J.F. Phylogeny and classification of the subfamily Rubioideae (Rubiaceae). Plant Syst. Evol., 2000, 225(1-4), 43-72.
[http://dx.doi.org/10.1007/BF00985458]
[31]
Patil, D.M.; Akamanchi, K.G. Ultrasound-assisted rapid extraction and kinetic modelling of influential factors: Extraction of camptothecin from Nothapodytes nimmoniana plant. Ultrason. Sonochem., 2017, 37, 582-591.
[http://dx.doi.org/10.1016/j.ultsonch.2017.02.015] [PMID: 28427671]
[32]
Kumara, P.A.A.S.P. Screening of Ophiorrhiza species and its endophytic microorganism for the production of camptothecin in Sri Lanka. MSc Thesis, The Australian National University: Canberra, 2019.
[33]
Landim, L.P.; Feitoza, G.S.; Costa, J.G.M. Development and validation of a HPLC method for the quantification of three flavonoids in a crude extract of Dimorphandra gardneriana. Rev. Bras. Farmacogn., 2013, 23(1), 58-64.
[http://dx.doi.org/10.1590/S0102-695X2013000100008]
[34]
Joseph, G. In Vivo And In Vitro Production Of CamptothecinIn Ophiorrhiza Species; MahathmaGandhi University: Kerala, India, 2011.
[35]
Montoro, P.; Maldini, M.; Piacente, S.; Macchia, M.; Pizza, C. Metabolite fingerprinting of Camptotheca acuminata and the HPLC–ESI-MS/MS analysis of camptothecin and related alkaloids. J. Pharm. Biomed. Anal., 2010, 51(2), 405-415.
[http://dx.doi.org/10.1016/j.jpba.2009.05.013] [PMID: 19520541]
[36]
Roja, G. Comparative studies on the camptothecin content from Nothapodytes foetida and Ophiorrhiza species. Nat. Prod. Res., 2006, 20(1), 85-88.
[http://dx.doi.org/10.1080/15216540500092898] [PMID: 16286315]
[37]
(a) Rajan, R.; Varghese, S.C.; Kurup, R.; Gopalakrishnan, R.; Venkataraman, R.; Satheeshkumar, K.; Baby, S. HPTLC-based quantification of camptothecin in Ophiorrhiza species of the southern Western Ghats in India. Cogent Chem., 2016, 2(1), 1275408.
[http://dx.doi.org/10.1080/23312009.2016.1275408];
(b) Mingzhang, A.; Jing, W.; Yue, S.; Wentao, G.; Longjiang, Y. Camptothecin distribution and content in Nothapodytes nimmoniana. Nat. Prod. Commun., 2011, 6(2), 1934578X1100600.
[http://dx.doi.org/10.1177/1934578X1100600210] [PMID: 21425673]
[38]
Liu, Z.; Adams, J. Camptothecin yield and distribution within Camptotheca acuminata trees cultivated in Louisiana. Can. J. Bot., 1996, 74(3), 360-365.
[http://dx.doi.org/10.1139/b96-045]

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