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
Research Article

Synthesis of Metal Complexes of Primaquine and In-vitro Antimalarial Evaluation Against Plasmodium falciparum

Author(s): Rimmy Nandal, Aakash Deep*, Ishwar Singh, Meenakshi Kaushik, Hoti S. L., Balasubramanian Narasimhan, Rakesh K. Marwaha and Arun K. Sharma

Volume 15, Issue 6, 2019

Page: [631 - 636] Pages: 6

DOI: 10.2174/1573407214666180720124844

Price: $65

Abstract

Background: Resistance to malarial drugs represents a major obstacle in the treatment of disease, thereby increasing the need for more efficient drugs. The development of metal complexes offers the medicinal chemist an opportunity to expand the activity of drugs. For providing supportive therapy to the host to boost its immune system several new antimalarial drugs are being beneath research, but sufficient information on their efficacy is yet not available.

Methods: In view of above, eight drug metal complexes (Ba (II), Ca (II), Zn (II), St (II), Hg (II), Fe (III), Cu (II), Ni (II) of Sulfamethoxazole (SMX) and Primaquine were synthesized and in-vitro evaluated for their antimalarial activity against malaria parasite Plasmodium falciparum by using fluorescence based assay.

Result: The antimalarial activity of Nickel (EC50= 1.41µM) and Zinc (EC50=0.96µM) complexes have shown tremendous activity as compared to the standard drug Primaquine (EC50=0.07µM). The structures of all these newly synthesized derivatives were confirmed by spectral data (IR, 1H NMR, 13C NMR and Mass spectrometry).

Conclusion: In conclusion, this study describes that the preparation and antimalarial evaluation of metal complexes of primaquine and sulphamethoxazole. Evaluation of their possible biological activities such as antimalarial activity was carried out and most of the synthesized compounds (Nickel and Zinc metal complexes) showed the good activity as compared to the standard drug primaquine. Therefore the compounds are appropriate candidates for more investigation and some more derivatives can be synthesized to get an imminent into the structure activity relationship of these compounds to be employed as biologically useful agents.

Keywords: Primaquine, metal complexes, antimalarial drugs, inflammation, morbidity, Plasmodium falciparum.

Graphical Abstract

[1]
Marcsisin, S.R.; Reichard, G.; Pybus, B.S. Primaquine pharmacology in the context of CYP 2D6 pharmacogenomics: Current state of the art. Pharmacol. Ther., 2016, 161, 1-10.
[http://dx.doi.org/10.1016/j.pharmthera.2016.03.011] [PMID: 27016470]
[2]
Guerin, P.J.; Olliaro, P.; Nosten, F.; Druilhe, P.; Laxminarayan, R.; Binka, F.; Kilama, W.L.; Ford, N.; White, N.J. Malaria: Current status of control, diagnosis, treatment, and a proposed agenda for research and development. Lancet Infect. Dis., 2002, 2(9), 564-573.
[http://dx.doi.org/10.1016/S1473-3099(02)00372-9] [PMID: 12206972]
[3]
Thomas, D.; Tazerouni, H.; Sundararaj, K.G.S.; Cooper, J.C. Therapeutic failure of primaquine and need for new medicines in radical cure of Plasmodium vivax. Acta Trop., 2016, 160, 35-38.
[http://dx.doi.org/10.1016/j.actatropica.2016.04.009] [PMID: 27109040]
[4]
Snow, R.W.; Trape, J.F.; Marsh, K. The past, present and future of childhood malaria mortality in Africa. Trends Parasitol., 2001, 17(12), 593-597.
[http://dx.doi.org/10.1016/S1471-4922(01)02031-1] [PMID: 11756044]
[5]
Breman, J.G.; Alilio, M.S.; Mills, A. Conquering the intolerable burden of malaria: What’s new, what’s needed: A summary. Am. J. Trop. Med. Hyg., 2004, 71(2)(Suppl.), 1-15.
[http://dx.doi.org/10.4269/ajtmh.2004.71.2_suppl.0700001] [PMID: 15331814]
[6]
White, N.J. Qinghaosu (artemisinin): The price of success. Science, 2008, 320(5874), 330-334.
[http://dx.doi.org/10.1126/science.1155165] [PMID: 18420924]
[7]
Narain, J.P. Malaria in the South-East Asia region: Myth & the reality. Indian J. Med. Res., 2008, 128(1), 1-3.
[http://dx.doi.org/10.4103/0971-5916.178571] [PMID: 18820349]
[8]
Murce, E.; Cuya-Guizado, T.R.; Padilla-Chavarria, H.I.; França, T.C.C.; Pimentel, A.S. Structure-based de novo design, molecular docking and molecular dynamics of primaquine analogues acting as quinone reductase II inhibitors. J. Mol. Graph. Model., 2015, 62, 235-244.
[http://dx.doi.org/10.1016/j.jmgm.2015.10.001] [PMID: 26521207]
[9]
Adediji, J.F.; Olayinka, E.T.; Adebayo, M.A.; Babatunde, O. Antimalarial mixed ligand metal complexes: Synthesis, physicochemical and biological activities. Int. J. Phys. Sci., 2009, 4(9), 529-534.
[10]
Hubin, T.J.; Amoyaw, P.N.A.; Roewe, K.D.; Simpson, N.C.; Maples, R.D.; Carder Freeman, T.N.; Cain, A.N.; Le, J.G.; Archibald, S.J.; Khan, S.I.; Tekwani, B.L.; Khan, M.O. Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands. Bioorg. Med. Chem., 2014, 22(13), 3239-3244.
[http://dx.doi.org/10.1016/j.bmc.2014.05.003] [PMID: 24857776]
[11]
Adediji, J.F.; Obaleye, J.A.; Akinremi, C.A. Ni(II) complex of mefloquine-pyrimethamine: Synthesis, toxicological andantimalarial activities against Plasmodium Berghei. J. Chem. Pharm. Res., 2012, 4(8), 4066-4072.
[12]
Phopin, K.; Sinthupoom, N.; Treeratanapiboon, L.; Kunwittaya, S.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Antimalarial and antimicrobial activities of 8-Aminoquinoline-Uracils metal complexes. EXCLI J., 2016, 15, 144-152.
[PMID: 27103894]
[13]
Murcea, M.; Cuya-Guizadob, T.R.; Padilla-Chavarriaa, H.I. Franc, TPhopin, K.; Sinthupoom, N.; Treeratanapiboon, L.; Kunwittaya, S.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, P. Antimalarial and antimicrobial activities of 8-aminoquinoline-uracils metal momplexes. EXCLI J., 2016, 15, 144-152.
[14]
Trager, W.; Jensen, J.B. Human malaria parasites in continuous culture. Science, 1976, 193(4254), 673-675.
[http://dx.doi.org/10.1126/science.781840] [PMID: 781840]
[15]
Malhotra, M.; Sharma, R.; Sanduja, M.; Kumar, R.; Jain, J.; Deep, A. Synthesis, characterization and evaluation of mannich bases as potent antifungal and hydrogen peroxide scavenging agents. Acta Pol. Pharm., 2012, 69(2), 355-361.
[PMID: 22568052]
[16]
Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods, 1983, 65(1-2), 55-63.
[http://dx.doi.org/10.1016/0022-1759(83)90303-4] [PMID: 6606682]

Rights & Permissions Print Cite
Article Metrics
11
© 2024 Bentham Science Publishers | Privacy Policy