Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

Antileishmanial Activity of Diterpene lactones from Suregada multiflora and Their Semisynthetic Derivatives

Author(s): Humaira Y. Gondal*, Muhammad Nisar and Muhammad I. Choudhary

Volume 16, Issue 1, 2020

Page: [53 - 57] Pages: 5

DOI: 10.2174/1573407214666180516101031

Price: $65

Abstract

Background: There is a general lack of effective and economical chemotherapeutic agents for the treatment of widely prevalent leishmanias. To develop locally available, low cost alternative therapy, a series of diterpene lactones isolated from Suregada multiflora and their semisynthetic derivatives have been evaluated against the protozoan parasite Leishmania.

Methods: A series of diterpene lactones were isolated from methanolic extract of Suregada multiflora. Major constituents were further derivatized through chemical and microbial transformations. Antileishmanial activity of structurally diverse diterpene lactones was performed by testing them in vitro against L. donovani promastigotes. All compounds were also tested for their cytotoxic effects by the brine shrimp bioassay.

Results: Among all compounds evaluated in current studies, natural diterpenes Gelomulide A (1) and G (2) were found significantly active with IC50 values below 20µg/ml. While, among synthesized derivatives; compounds 5, 9 and 10 were found more potent with IC50 value 17.49, 18.38 and 17.81µg/ml, respectively. None of these compounds showed cytotoxic effects in the brine shrimp bioassay (LC50> 300).

Conclusion: A new class of diterpene lactones was identified as potential antileshmanial agent. The structural diversity of natural and semisynthetic diterpene lactones, helped to rationalize structure– activity relationships. Activity of these diterpene lactones owed to C-8/14 epoxide along with unsubstituted C-1. Keto group at C-1 always lower the activity unless it is in α, β-unsaturated form. Presence of acetyl group at C-3 and 6 usually augmented the antileishmanila potential.

Keywords: Suregada multiflora, diterpene lactones, antileishmanial, leishmaniasis, spectrometer, pentavalent antimonials.

Graphical Abstract

[1]
World Health Organization. Special Programme for Research, & Training in Tropical Diseases. Tropical disease research, 2001.
[2]
WHO Expert Committee on the Control of the Leishmaniases. Meeting, & World Health Organization. Control of the Leish-maniases: Report of a WHO Expert Committee, 1990.
[3]
Desjeux, P. Leishmaniasis. Public health aspects and control. Clin. Dermatol., 1996, 14(5), 417-423.
[http://dx.doi.org/10.1016/0738-081X(96)00057-0] [PMID: 8889319]
[4]
Desjeux, P. Worldwide increasing risk factors for leishmaniasis. Med. Microbiol. Immunol. (Berl.), 2001, 190(1-2), 77-79.
[http://dx.doi.org/10.1007/s004300100085] [PMID: 11770116]
[5]
Handman, E. Leishmaniasis: current status of vaccine development. Clin. Microbiol. Rev., 2001, 14(2), 229-243.
[http://dx.doi.org/10.1128/CMR.14.2.229-243.2001] [PMID: 11292637]
[6]
DeCarvalho, P.B.; Arribas, M.D.G.; Ferreira, E.I. Leishmaniasis. What do we know about its chemotherapy? Revista Brasileira de Ciências Farmacêut., 2000, 36(1), 69-96.
[7]
Barral, A.; Pedral-Sampaio, D.; Grimaldi Júnior, G.; Momen, H.; McMahon-Pratt, D.; Ribeiro de Jesus, A.; Almeida, R.; Badaro, R.; Barral-Netto, M.; Carvalho, E.M. Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. Am. J. Trop. Med. Hyg., 1991, 44(5), 536-546.
[http://dx.doi.org/10.4269/ajtmh.1991.44.536] [PMID: 2063957]
[8]
Ashford, R.W. The leishmaniases as emerging and reemerging zoonoses. Int. J. Parasitol., 2000, 30(12-13), 1269-1281.
[http://dx.doi.org/10.1016/S0020-7519(00)00136-3] [PMID: 11113254]
[9]
Davis, A.J.; Kedzierski, L. Recent advances in antileishmanial drug development. Curr. Opin. Investigat. Drugs (London, England: 2000), 2005, 6(2), 163-169.
[10]
Davies, C.R.; Kaye, P.; Croft, S.L.; Sundar, S. Leishmaniasis: new approaches to disease control. BMJ, 2003, 326(7385), 377-382.
[http://dx.doi.org/10.1136/bmj.326.7385.377] [PMID: 12586674]
[11]
Garnier, T.; Croft, S.L. Topical treatment for cutaneous leishmaniasis. Curr. Opin. Investig. Drugs, 2002, 3(4), 538-544.
[PMID: 12090720]
[12]
Brenzan, M.A.; Nakamura, C.V.; Prado Dias Filho, B.; Ueda-Nakamura, T.; Young, M.C.M.; Aparício, G.C.D. Antileishmanial activity of crude extract and coumarin from Calophyllum brasiliense leaves against Leishmania amazonensis. Parasitol. Res., 2007, 101(3), 715-722.
[http://dx.doi.org/10.1007/s00436-007-0542-7] [PMID: 17483964]
[13]
Tiuman, T.S.; Santos, A.O.; Ueda-Nakamura, T.; Filho, B.P.; Nakamura, C.V. Recent advances in leishmaniasis treatment. Int. J. Infect. Dis., 2011, 15(8), e525-e532.
[http://dx.doi.org/10.1016/j.ijid.2011.03.021] [PMID: 21605997]
[14]
Olliaro, P.L.; Bryceson, A.D.M. Practical progress and new drugs for changing patterns of leishmaniasis. Parasitol. Today (Regul. Ed.), 1993, 9(9), 323-328.
[http://dx.doi.org/10.1016/0169-4758(93)90231-4] [PMID: 15463794]
[15]
Soto, J.; Arana, B.A.; Toledo, J.; Rizzo, N.; Vega, J.C.; Diaz, A.; Luz, M.; Gutierrez, P.; Arboleda, M.; Berman, J.D.; Junge, K.; Engel, J.; Sindermann, H. Miltefosine for new world cutaneous leishmaniasis. Clin. Infect. Dis., 2004, 38(9), 1266-1272.
[http://dx.doi.org/10.1086/383321] [PMID: 15127339]
[16]
Hirst, S.I.; Stapley, L.A. Parasitology: The dawn of a new millennium. Parasitol. Today (Regul. Ed.), 2000, 16(1), 1-3.
[http://dx.doi.org/10.1016/S0169-4758(99)01589-6] [PMID: 10637575]
[17]
Santos, D.O.; Coutinho, C.E.; Madeira, M.F.; Bottino, C.G.; Vieira, R.T.; Nascimento, S.B.; Bernardino, A.; Bourguignon, S.C.; Corte-Real, S.; Pinho, R.T.; Rodrigues, C.R.; Castro, H.C. Leishmaniasis treatment--a challenge that remains: a review. Parasitol. Res., 2008, 103(1), 1-10.
[http://dx.doi.org/10.1007/s00436-008-0943-2] [PMID: 18389282]
[18]
Kayser, O.; Kiderlen, A.F. In vitro leishmanicidal activity of naturally occurring chalcones. Phytother. Res., 2001, 15(2), 148-152.
[http://dx.doi.org/10.1002/ptr.701] [PMID: 11268116]
[19]
Kedzierski, L. Leishmaniasis vaccine: Where are we today? J. Glob. Infect. Dis., 2010, 2(2), 177-185.
[http://dx.doi.org/10.4103/0974-777X.62881] [PMID: 20606974]
[20]
Srivastava, S.; Shankar, P.; Mishra, J.; Singh, S. Possibilities and challenges for developing a successful vaccine for leishmaniasis. Parasit. Vectors, 2016, 9(1), 277.
[http://dx.doi.org/10.1186/s13071-016-1553-y] [PMID: 27175732]
[21]
Rocha, L.G.; Almeida, J.R.G.S.; Macêdo, R.O.; Barbosa-Filho, J.M. A review of natural products with antileishmanial activity. Phytomedicine, 2005, 12(6-7), 514-535.
[http://dx.doi.org/10.1016/j.phymed.2003.10.006] [PMID: 16008131]
[22]
Adebayo, O.L.; Suleman, D.; Samson, A.A. Natural products in antileishmanial drug discovery: A review. J. Asian Sci. Res., 2013, 3(2), 157.
[23]
Pan, L.; Lezama-Davila, C.M.; Isaac-Marquez, A.P.; Fuchs, J.R.; Satoskar, A.R.; Kinghorn, A.D. Compounds with antileishmanial activity isolated from the stems of Pentalinon andrieuxii. Planta Med., 2012, 78(11), 239.
[http://dx.doi.org/10.1055/s-0032-1320926]
[24]
Rojas-Silva, P.; Graziose, R.; Poulev, A.; Mbeunkui, F.; Grace, M.H.; Lila, M.A.; Raskin, I. Seeking novel Leishmanicidal natural products from common medicinal plants, the example of Eryngium foetidum L. Planta Med., 2012, 78(11), 87.
[http://dx.doi.org/10.1055/s-0032-1320634]
[25]
de Carvalho, P.B.; Ferreira, E.I. Leishmaniasis phytotherapy. Nature’s leadership against an ancient disease. Fitoterapia, 2001, 72(6), 599-618.
[http://dx.doi.org/10.1016/S0367-326X(01)00301-X] [PMID: 11543959]
[26]
Fokialakis, N.; Kalpoutzakis, E.; Tekwani, B.L.; Skaltsounis, A.L.; Duke, S.O. Antileishmanial activity of natural diterpenes from Cistus sp. and semisynthetic derivatives thereof. Biol. Pharm. Bull., 2006, 29(8), 1775-1778.
[http://dx.doi.org/10.1248/bpb.29.1775] [PMID: 16880643]
[27]
Choudhary, M.I.; Gondal, H.Y.; Abbaskhan, A.; Jahan, I.A.; Parvez, M.; Nahar, N. Revisiting diterpene lactones of Suregada multiflora. Tetrahedron, 2004, 60(36), 7933-7941.
[http://dx.doi.org/10.1016/j.tet.2004.06.047]
[28]
Gondal, H.Y.; Choudhary, M.I. New diterpene lactone from leaves of Suregada multiflora. Chem. Nat. Compd., 2016, 52(3), 421-423.
[http://dx.doi.org/10.1007/s10600-016-1663-y]
[29]
Choudhary, M.I.; Gondal, H.Y.; Abbaskhan, A. Microbial transformations of gelomulide G: a member of the rare class of diterpene lactones. Chem. Biodivers., 2005, 2(10), 1401-1408.
[http://dx.doi.org/10.1002/cbdv.200590112] [PMID: 17191941]
[30]
Gondal, H.Y.; Choudhary, M.I. Chemical and biotransformation of Gelomulide F: A rare diterpene lactone. Turk. J. Chem., 2012, 36(5), 759-763.

Rights & Permissions Print Cite
Article Metrics
13
World Immunization Week
© 2024 Bentham Science Publishers | Privacy Policy