Review Article

An Insight into the Discovery of Potent Antifilarial Leads Against Lymphatic Filariasis

Author(s): Pone Kamdem Boniface* and Ferreira Igne Elizabeth

Volume 21, Issue 7, 2020

Page: [657 - 680] Pages: 24

DOI: 10.2174/1389450120666191204152415

Price: $65

Abstract

Background and Objectives: Lymphatic filariasis is a neglected tropical disease caused by infection with filarial worms that are transmitted through mosquito bites. Globally, 120 million people are infected, with nearly 40 million people disfigured and disabled by complications such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). Current treatments (ivermectin, diethylcarbamazine) have limited effects on adult parasites and produce side effects; therefore, there is an urgent to search for new antifilarial agents. Numerous studies on the antifilarial activity of pure molecules have been reported accross the recent literature. The present study describes the current standings of potent antifilarial compounds against lymphatic filariasis.

Methods: A literature search was conducted for naturally occurring and synthetic antifilarial compounds by referencing textbooks and scientific databases (SciFinder, PubMed, Science Direct, Wiley, ACS, SciELO, Google Scholar, and Springer, among others) from their inception until September 2019.

Results: Numerous compounds have been reported to exhibit antifilarial acitivity in adult and microfilariae forms of the parasites responsible for lymphatic filariasis. In silico studies of active antifilarial compounds (ligands) showed molecular interactions over the protein targets (trehalose-6-phosphate phosphatase, thymidylate synthase, among others) of lymphatic filariasis, and supported the in vitro results.

Conclusion: With reference to in vitro antifilarial studies, there is evidence that natural and synthetic products can serve as basic scaffolds for the development of antifilarial agents. The optimization of the most potent antifilarial compounds can be further performed, followed by their in vivo studies.

Keywords: Neglected tropical diseases, lymphatic filariasis, brugia malayi, natural products, synthesis, medicinal chemistry.

Graphical Abstract
[1]
Boniface PK, Ferreira EI. Flavonoids as efficient scaffolds: Recent trends for malaria, leishmaniasis, Chagas disease, and dengue. Phytother Res 2019; 33(10): 2473-517. [http://dx.doi.org/10.1002/ptr.6383]
[PMID: 31441148]
[2]
Lymphatic filariasis https://www.who.int/lymphatic_filariasis/en/ [25th September 2019]
[3]
Mathew N, Misra-Bhattacharya S, Perumal V, Muthuswamy K. Antifilarial lead molecules isolated from Trachyspermum ammi. Molecules 2008; 13(9): 2156-68. [http://dx.doi.org/10.3390/molecules13092156]
[PMID: 18830147]
[4]
Cano J, Rebollo MP, Golding N, et al. The global distribution and transmission limits of lymphatic filariasis: past and present. Parasit Vectors 2014; 7: 466. [http://dx.doi.org/10.1186/s13071-014-0466-x]
[PMID: 25303991]
[5]
Sheel M, Sheridan S, Gass K, et al. Identifying residual transmission of lymphatic filariasis after mass drug administration: Comparing school-based versus community-based surveillance - American Samoa, 2016. PLoS Negl Trop Dis 2018; 12(7)e0006583 [http://dx.doi.org/10.1371/journal.pntd.0006583]
[PMID: 30011276]
[6]
Lakshmi V, Joseph SK, Srivastava S, et al. Antifilarial activity in vitro and in vivo of some flavonoids tested against Brugia malayi. Acta Trop 2010; 116(2): 127-33. [http://dx.doi.org/10.1016/j.actatropica.2010.06.006]
[PMID: 20609356]
[7]
Misra S, Singh LK, Priyanka , Gupta J, Misra-Bhattacharya S, Katiyar D. Synthesis and biological evaluation of 4-oxycoumarin derivatives as a new class of antifilarial agents. Eur J Med Chem 2015; 94: 211-7. [http://dx.doi.org/10.1016/j.ejmech.2015.02.043]
[PMID: 25768703]
[8]
Senathilake KS, Karunanayake EH, Samarakoon SR, Tennekoon KH, de Silva ED, Adhikari A. Oleanolic acid from antifilarial triterpene saponins of Dipterocarpus zeylanicus induces oxidative stress and apoptosis in filarial parasite Setaria digitata in vitro. Exp Parasitol 2017; 177: 13-21. [http://dx.doi.org/10.1016/j.exppara.2017.03.007]
[PMID: 28351683]
[9]
Muhammad A, Funmilola A, Aimola IA, Ndams IS, Inuwa MH, Nok AJ. Kolaviron shows anti-proliferative effect and down regulation of vascular endothelial growth factor-C and toll like receptor-2 in Wuchereria bancrofti infected blood lymphocytes. J Infect Public Health 2017; 10(5): 661-6. [http://dx.doi.org/10.1016/j.jiph.2017.05.006]
[PMID: 28619504]
[10]
Tyagi R, Verma S, Mishra S, et al. In vitro and in silico studies of glycyrrhetinic acid derivatives as anti-filarial agents. Curr Top Med Chem 2019; 19(14): 1191-200. [http://dx.doi.org/10.2174/1568026619666190618141450]
[PMID: 31210109]
[11]
Nutman TB. Insights into the pathogenesis of disease in human lymphatic filariasis. Lymphat Res Biol 2013; 11(3): 144-8. [http://dx.doi.org/10.1089/lrb.2013.0021]
[PMID: 24044755]
[12]
Mandal A. What is elephanthiasis? News-Medicalnet https://www.news-medical.net/?tag=/Elephantiasis [10th September 2019]
[13]
Stocks ME, Freeman MC, Addiss DG. The effect of hygiene-based lymphedema management in lymphatic filariasis-endemic areas: A systematic review and meta-analysis. 2015). PLoS Negl Trop Dis 2015; 9(10)e0004171 [http://dx.doi.org/10.1371/journal.pntd.0004171]
[PMID: 26496129]
[14]
Komoreng L, Thekisoe O, Lehasa S, et al. An ethnobotanical survey of traditional medicinal plants used against lymphatic filariasis in South Africa. S Afr J Bot 2017; 111: 12-6. [http://dx.doi.org/10.1016/j.sajb.2017.03.005].
[15]
Norões J, Dreyer G. A mechanism for chronic filarial hydrocele with implications for its surgical repair. PLoS Negl Trop Dis 2010; 4(6)e695 [http://dx.doi.org/10.1371/journal.pntd.0000695]
[PMID: 20532225]
[16]
Goel TC, Goel A. Clinical manifestations of filariasis.Lymphatic filariasis 2017; 111-8
[17]
Prodjinotho UF, von Horn C, Debrah AY, et al. Pathological manifestations in lymphatic filariasis correlate with lack of inhibitory properties of IgG4 antibodies on IgE-activated granulocytes. PLoS Negl Trop Dis 2017; 11(7)e0005777 [http://dx.doi.org/10.1371/journal.pntd.0005777]
[PMID: 28742098]
[18]
Rai P, Bharati M, Subba A, Saha D. Insecticide resistance mapping in the vector of lymphatic filariasis, Culex quinquefasciatus Say from northern region of West Bengal, India. PLoS One 2019; 14(5)e0217706 [http://dx.doi.org/10.1371/journal.pone.0217706]
[PMID: 31141548]
[19]
Simonsen PE, Fischer PU, Hoerauf A, et al. The filariases. manson’s tropical diseases 23rd ed. 2014; 737-65. [http://dx.doi.org/10.1016/B978-0-7020-5101-2.00055-8]
[20]
Shenoy RK. Clinical and pathological aspects of filarial lymphedema and its management. Korean J Parasitol 2008; 46(3): 119-25. [http://dx.doi.org/10.3347/kjp.2008.46.3.119]
[PMID: 18830049]
[21]
Famakinde DO. Mosquitoes and the lymphatic filarial parasites: research trends and budding roadmaps to future disease eradication Trop Med Infect Dis 2018; 3(1): pii-E4 [http://dx.doi.org/10.3390/tropicalmed3010004]
[22]
Chakraborty S, Gurusamy M, Zawieja DC, Muthuchamy M. Lymphatic filariasis: perspectives on lymphatic remodeling and contractile dysfunction in filarial disease pathogenesis. Microcirculation 2013; 20(5): 349-64. [http://dx.doi.org/10.1111/micc.12031]
[PMID: 23237232]
[23]
Dickson BFR, Graves PM, Aye NN, et al. The prevalence of lymphatic filariasis infection and disease following six rounds of mass drug administration in Mandalay Region, Myanmar. PLoS Negl Trop Dis 2018; 12(11)e0006944 [http://dx.doi.org/10.1371/journal.pntd.0006944]
[PMID: 30419025]
[24]
Nuchprayoon S. DNA-based diagnosis of lymphatic filariasis. Southeast Asian J Trop Med Public Health 2009; 40(5): 904-13.
[PMID: 19842372]
[25]
Pion SD, Montavon C, Chesnais CB, et al. Positivity of antigen tests used for diagnosis of lymphatic filariasis in individuals without wuchereria bancrofti infection but with high Loa loa microfilaremia. Am J Trop Med Hyg 2016; 95(6): 1417-23. [http://dx.doi.org/10.4269/ajtmh.16-0547]
[PMID: 27729568]
[27]
Gyapong JO, Owusu IO, da-Costa Vroom FB, Mensah EO, Gyapong M. Elimination of lymphatic filariasis: current perspectives on mass drug administration. Res Rep Trop Med 2018; 9: 25-33. [http://dx.doi.org/10.2147/RRTM.S125204]
[PMID: 30050352]
[28]
Hoerauf A. Filariasis: new drugs and new opportunities for lymphatic filariasis and onchocerciasis. Curr Opin Infect Dis 2008; 21(6): 673-81. [http://dx.doi.org/10.1097/QCO.0b013e328315cde7]
[PMID: 18978537]
[29]
Taylor MJ, Hoerauf A, Bockarie M. Lymphatic filariasis and onchocerciasis. Lancet 2010; 376(9747): 1175-85. [http://dx.doi.org/10.1016/S0140-6736(10)60586-7]
[PMID: 20739055]
[30]
Odermatt P, Leang R, Bin B, Bunkea T, Socheat D. Prevention of lymphatic filariasis with insecticide-treated bednets in Cambodia. Ann Trop Med Parasitol 2008; 102(2): 135-42. [http://dx.doi.org/10.1179/136485908X252313]
[PMID: 18318935]
[31]
Bockarie MJ, Molyneux DH. The end of lymphatic filariasis? BMJ 2009; 338: b1686. [http://dx.doi.org/10.1136/bmj.b1686]
[PMID: 19439451]
[32]
de Souza DK, Koudou B, Kelly-Hope LA, Wilson MD, Bockarie MJ, Boakye DA. Diversity and transmission competence in lymphatic filariasis vectors in West Africa, and the implications for accelerated elimination of Anopheles-transmitted filariasis. Parasit Vectors 2012; 5: 259. [http://dx.doi.org/10.1186/1756-3305-5-259]
[PMID: 23151383]
[33]
Cho SH, Ma DW, Koo BR, et al. Surveillance and vector control of lymphatic filariasis in the republic of Korea. Osong Public Health Res Perspect 2012; 3(3): 145-50. [http://dx.doi.org/10.1016/j.phrp.2012.07.008]
[PMID: 24159506]
[34]
Misra N, Sharma M, Raj K, Dangi A, Srivastava S, Misra-Bhattacharya S. Chemical constituents and antifilarial activity of Lantana camara against human lymphatic filariid Brugia malayi and rodent filariid Acanthocheilonema viteae maintained in rodent hosts. Parasitol Res 2007; 100(3): 439-48. [http://dx.doi.org/10.1007/s00436-006-0312-y]
[PMID: 17061115]
[35]
Misra S, Verma M, Mishra SK, Srivastava S, Lakshmi V, Misra-Bhattacharya S. Gedunin and photogedunin of Xylocarpus granatum possess antifilarial activity against human lymphatic filarial parasite Brugia malayi in experimental rodent host. Parasitol Res 2011; 109(5): 1351-60. [http://dx.doi.org/10.1007/s00436-011-2380-x]
[PMID: 21523424]
[36]
Kushwaha S, Soni VK, Singh PK, et al. Withania somnifera chemotypes NMITLI 101R, NMITLI 118R, NMITLI 128R and withaferin A protect Mastomys coucha from Brugia malayi infection. Parasite Immunol 2012; 34(4): 199-209. [http://dx.doi.org/10.1111/j.1365-3024.2012.01352.x]
[PMID: 22394222]
[37]
Sashidhara KV, Singh SP, Misra S, Gupta J, Misra-Bhattacharya S. Galactolipids from Bauhinia racemosa as a new class of antifilarial agents against human lymphatic filarial parasite, Brugia malayi. Eur J Med Chem 2012; 50: 230-5. [http://dx.doi.org/10.1016/j.ejmech.2012.01.057]
[PMID: 22348826]
[38]
Azeez S, Babu RO, Aykkal R, Narayanan R. Virtual screening and in vitro assay of potential drug like inhibitors from spices against glutathione-S-transferase of filarial nematodes. J Mol Model 2012; 18(1): 151-63. [http://dx.doi.org/10.1007/s00894-011-1035-2]
[PMID: 21523552]
[39]
Saini P, Gayen P, Nayak A, et al. Effect of ferulic acid from Hibiscus mutabilis on filarial parasite Setaria cervi: molecular and biochemical approaches. Parasitol Int 2012; 61(4): 520-31. [http://dx.doi.org/10.1016/j.parint.2012.04.002]
[PMID: 22562003]
[40]
Yadav D, Kushwaha V, Saxena K, Verma R, Murthy PK, Gupta MM. Diarylheptanoid compounds from Alnus nepalensis express in vitro and in vivo antifilarial activity. Acta Trop 2013; 128(3): 509-17. [http://dx.doi.org/10.1016/j.actatropica.2013.07.015]
[PMID: 23911333]
[41]
Yadav D, Singh SC, Verma RK, et al. Antifilarial diarylheptanoids from Alnus nepalensis leaves growing in high altitude areas of Uttarakhand, India. Phytomedicine 2013; 20(2): 124-32. [http://dx.doi.org/10.1016/j.phymed.2012.10.017]
[PMID: 23219341]
[42]
Kalani K, Kushwaha V, Sharma P, et al. In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent. PLoS One 2014; 9(11)e111244 [http://dx.doi.org/10.1371/journal.pone.0111244]
[PMID: 25375886]
[43]
Kushwaha V, Saxena K, Verma R, et al. Antifilarial activity of diterpenoids from Taxodium distichum. Parasit Vectors 2016; 9(1): 312. [http://dx.doi.org/10.1186/s13071-016-1592-4]
[PMID: 27245322]
[44]
Rana G. Inhibition efficiency of a newly isolated flavonoid compound from Vitex negundo L. leaves against cattle-endosymbiont Setaria cervi: Phytomedicine for lymphatic filariasis. Parasite Epidemiol Control 2018; 3(2): 88-95. [http://dx.doi.org/10.1016/j.parepi.2018.03.002]
[PMID: 29988277]
[45]
Kalani K, Kushwaha V, Verma R, Murthy PK, Srivastava SK. Glycyrrhetinic acid and its analogs: a new class of antifilarial agents. Bioorg Med Chem Lett 2013; 23(9): 2566-70. [http://dx.doi.org/10.1016/j.bmcl.2013.02.115]
[PMID: 23541646]
[46]
Singh VK, Doharey PK, Kumar V, et al. Synthesis, molecular docking and Brugia malayi thymidylate kinase (BmTMK) enzyme inhibition study of novel derivatives of [6]-shogaol. Eur J Med Chem 2015; 93: 74-82. [http://dx.doi.org/10.1016/j.ejmech.2015.01.035]
[PMID: 25659753]
[47]
Bahekar SP, Hande SV, Agrawal NR, et al. Sulfonamide chalcones: Synthesis and in vitro exploration for therapeutic potential against Brugia malayi. Eur J Med Chem 2016; 124: 262-9. [http://dx.doi.org/10.1016/j.ejmech.2016.08.042]
[PMID: 27592395]
[48]
Gandhi MR, Reegan AD, Ganesan P, et al. Larvicidal and pupicidal activities of alizarin isolated from roots of Rubia cordifolia against Culex quinquefasciatus Say and Aedes aegypti (L.) (Diptera: Culicidae). Neotrop Entomol 2016; 45(4): 441-8. [http://dx.doi.org/10.1007/s13744-016-0386-x]
[PMID: 27004695]
[49]
Govindarajan M, Rajeswary M, Benelli G. Chemical composition, toxicity and non-target effects of Pinus kesiya essential oil: An eco-friendly and novel larvicide against malaria, dengue and lymphatic filariasis mosquito vectors. Ecotoxicol Environ Saf 2016; 129: 85-90 a.
[http://dx.doi.org/10.1016/j.ecoenv.2016.03.007] [PMID: 26995063]
[50]
Govindarajan M, Rajeswary M, Arivoli S, Tennyson S, Benelli G. Larvicidal and repellent potential of Zingiber nimmonii (J. Graham) Dalzell (Zingiberaceae) essential oil: an eco-friendly tool against malaria, dengue, and lymphatic filariasis mosquito vectors? Parasitol Res 2016; 115(5): 1807-16. [http://dx.doi.org/10.1007/s00436-016-4920-x]
[PMID: 26792432]
[51]
Madhu SK, Shaukath AK, Vijayan VA. Efficacy of bioactive compounds from Curcuma aromatica against mosquito larvae. Acta Trop 2010; 113(1): 7-11. [http://dx.doi.org/10.1016/j.actatropica.2009.08.023]
[PMID: 19712662]
[52]
Madhu SK, Vijayan VA, Shaukath AK. Bioactivity guided isolation of mosquito larvicide from Piper longum. Asian Pac J Trop Med 2011; 4(2): 112-6. [http://dx.doi.org/10.1016/S1995-7645(11)60048-5]
[PMID: 21771432]
[53]
Subashini R, Bharathi A, Roopan SM, Rajakumar G, Abdul Rahuman A, Gullanki PK. Synthesis, spectral characterization and larvicidal activity of acridin-1(2H)-one analogues. Spectrochim Acta A Mol Biomol Spectrosc 2012; 95: 442-5. [http://dx.doi.org/10.1016/j.saa.2012.04.015]
[PMID: 22579326]
[54]
Lakshmi Ranganatha V, Bushra Begum A, Prashanth T, et al. Synthesis and larvicidal properties of benzophenone comprise indole analogues against Culex quinquefasciatus. Drug Invent Today 2013; 5: 275-80. [http://dx.doi.org/10.1016/j.dit.2013.10.001]
[55]
Peixoto CA, Rocha A, Aguiar-Santos A, Florêncio MS. The effects of diethylcarbamazine on the ultrastructure of microfilariae of Wuchereria bancrofti in vivo and in vitro. Parasitol Res 2004; 92(6): 513-7. [http://dx.doi.org/10.1007/s00436-004-1081-0]
[PMID: 15007641]
[56]
Harrow ID, Gration KAF. Mode of action of morantel, pyrantel, and levamisole on muscle cell membrane of the nematode Ascaris suum. Pestic Sci 1985; 16: 662-75. [http://dx.doi.org/10.1002/ps.2780160612].
[57]
Sani BP, Vaid A. Specific interaction of ivermectin with retinol-binding protein from filarial parasites. Biochem J 1988; 249(3): 929-32. [http://dx.doi.org/10.1042/bj2490929]
[PMID: 3355505]
[58]
Pandaya U, Shukla OP. Suramin destabilises the secondary structure of filarial DNA. Med Sci Res 1994; 22: 833-4.
[59]
Boniface PK, Elizabeth FI. Flavonoid-derived privileged scaffolds in anti-trypanosoma brucei drug discovery. Curr Drug Targets 2019; 20(12): 1295-1314 b.
[http://dx.doi.org/10.2174/1389450120666190618114857] [PMID: 31215385]
[60]
Don R, Ioset JR. Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections. Parasitology 2014; 141(1): 140-6. [http://dx.doi.org/10.1017/S003118201300142X]
[PMID: 23985066]
[61]
Pluta K, Morak-Młodawska B, Jeleń M. Recent progress in biological activities of synthesized phenothiazines. Eur J Med Chem 2011; 46(8): 3179-89. [http://dx.doi.org/10.1016/j.ejmech.2011.05.013]
[PMID: 21620536]
[62]
Hou J, Feng C, Li Z, et al. Structure-based optimization of click-based histone deacetylase inhibitors. Eur J Med Chem 2011; 46(8): 3190-200. [http://dx.doi.org/10.1016/j.ejmech.2011.04.027]
[PMID: 21621883]
[63]
Subrahmanyam D. Antifilarials and their mode of action. Ciba Found Symp 1987; 127: 246-64. [PMID: 3297557].
[PMID: 3297557]
[64]
Köhler P, Davies KP, Zahner H. Activity, mechanism of action and pharmacokinetics of 2-tert-butylbenzothiazole and CGP 6140 (amocarzine) antifilarial drugs. Acta Trop 1992; 51(3-4): 195-211. [http://dx.doi.org/10.1016/0001-706X(92)90038-Y]
[PMID: 1359747]
[65]
Sharma B. Lymphatic filariasis and chemotherapeutic targets. Biochem Anal Biochem 2014; 3: 1.

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