SYNTHESIS, DOCKING AND EVALUATION OF PYRIMIDINE DERIVATIVES AS ANTI-MALARIAL AGENTS
DOI:
https://doi.org/10.61280/tjpls.v10i5.145Keywords:
Molecular docking, Pyrimidine Derivatives, Anti-Malarial Agents, Protozoan disease, Computer aided drug designAbstract
Malaria is endmic disease of tropical and subtropical contries like India, Pakistan, Srilanka, Bangladesh, South Africa etc. There are lot of fatalities and causalities due to malaria every year. There are lot of drugs have been synthesized for controlling this intermittent fever like chloroquine, hydroxychloroquine, pamaquine, primaquine, artimisininine, sulphadoxine, pyrimethamine, dapsone. The pyrimidine derivative synthetic drugs like sulphadoxine and pyramethamine have potential role to treat malaria with fever side effects. The lead molecule is pyrimdine and various groups are attached to this nucleus for optimizing the activity of lead nucleus and its derivative to treat this dangerous disease.
The main causative organisms are plasmodium falciparm, plasmodium vivex, plasmodium malariae and ovale that cause malaria in patient and transmitted in blood after bitting of female anopheles mosquito that act as vector for plasmodium species.
The docking studies are also performed by software and proper lead compound is identified with docking studies. The synthesis of compounds were carried out in laboratories with microwave synthesis and newer techniques that are fast and less time consuming of better yield of products. Structure activities relationships are studied and optimum activities are obtained by replacing different functional groups and other groups.
Downloads
References
Ashley E, McGready R, Proux S, Nosten F. Malaria .Travel Med. Infect. Dis. 2006; 4: 159-173.
Kumar A, Katiyar SB, Agawal A, Chauhan PMS. Perspective in Antimalarial Chemotherapy.Curr.Med. Chem. 2003; 10: 1137-1150.
http://www.who.int/mediacentre/factsheets/fs094/en/index.html.
a) http://www.rollbackmalaria.org/wmr2005/pdf/intro_section.pdf.
b) http://www.rollbackmalaria.org/wmr2005/pdf/section2.pdf.
www.niaid.nih.gov/topics/malaria/documents/malaria.pdf.
Kumar A, Katiyar SB, Agawal A, Chauhan PMS.Perspective in antimalarial chemotherapy .Curr. Med. Chem. 2003; 10: 1137-1150.
Stocks PA, Raynes KJ, Ward SA. Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery (Ed.: P. J. Rosenthal), Humana, Totowa. 2001; 235-253.
Wellems TE, Plowe CV. Chloroquine resistant malaria .J. Infect. Dis. 2001; 184: 770-776.
Hastings IM. The origins of antimalarial drug resistance .Trends Parasitol. 2004; 20:512-518.
Ginsburg H.Acta Trop. Should chloroquine be laid to rest? 2005; 96:16-23.
Meshnick SR. Why does quinine still work after 350 years of use? Parasitol. Today1997; 13:89-90.
Kevin BJ. Effectiveness of antimalarial drugs. N. Engl. J. Med. 2005; 352: 1565-1577.
Suh KN, Kain KC, Keystone JS. Malaria. Can. Med. Assoc. J. 2004; 170: 1693- 1702.
Pasvol G.Management of severe malaria: interventions and controversies. Infect. Dis. Clin. N. Am. 2005; 19: 211-240.
http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf.
Taylor WRJ, White NJ. Antimalarial drug toxicity: a review .Drug Saf. 2004; 27: 25-61.
Haynes RK, Vonwiller SC. From Qinghao, Marvelous Herb of Antiquity, to the Antimalarial Trioxane Qinghaosu - and Some Remarkable New Chemistry .Acc. Chem. Res.1997; 30: 73-79.
Schmuck G, Roehrdanz E, Haynes RK, Kahl R. Neurotoxic Mode of Action of Artemisinin Antimicrob. Agents Chemother. 2002:46: 821-827.
Franck X, Fournet A, Prina E, Mahieux R, Hocquemiller R, Figadere B. Biological evaluation of substituted quinazolines. Bioorg. Med. Chem. Lett. 2004, 14, 3635.
Winter RW, Cornell KA, Johnson LL, Isabelle LM, Hinrichs DJ, Riscoe MK. Hydroxy anthraquinazones as antimalarial agents. Bioorg. Med.Chem. Lett. 1995, 5, 1927.
Francois G, Timperman G, Eling W, Assi LA, Holenz J, Brigmann G. Naphthylisoquinazoline alkaloids against malaria: evaluation of curative potentials of dioncophylline C and dioncopeltine A against Plasmodium berghei in vivo. Antimicrob. Agents Chemother. 1997, 41, 2533.
Konig GM, Wright AD, Sticher O, Fronczek F. Two new sesquiterpenes isothiocyanates from marine sponge Acanthella klethra. J. Nat. Prod. 1992, 55, 633.
Radloff PD, Philipps J, Nkeyi M, Hutchinson D, Kremsner PG. Atovaquone and proguanil for Plasmodium falciparum malaria. Lancet, 1996, 347, 1511.
Chen M, Christensen SB, Zhai L, Rasmussen MH, Theander TG, Frokjaer S, Steffansen B, Davidsen J, Kharazmi A. The novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivoJ. infect. Dis.1997, 176, 1327.
Francois G, Bringmann G, Dochez C, Schneider C, Timperman G. Assi, L. A. Activities of extracts and naphthylisoquinazoline alkaloids from Triphyophyllum peltatum, Ancistrocladus abbreviatus and Ancistrocladus barteri against Plasmodium berghei (Anka strain) in vitro.J.Ethanopharmacol.1995, 46, 115.
Singh SB, Zink DL, Polishook JD, Dombrowski AW, Darkin-Rattray SJ, Schmatz DM, Goetz MA. Apicidins: Novel cyclic tetrapeptides as coccidiostats and antimalarial agents from Fusarium pallidoroseum. Tetrahedron Lett. 1996;37:8077.
Ancelin M, Calas M, Vidal-Sailhan V, Herbute S, Ringwald P, Vial H. Potential inhibitors of Plasmodium phospholipid metabolism with a broad spectrum of in vitro antimalarial activities. Antimicrob Agents Chemother. 2003; 47:2590.
Martin RE, Henry RI, Abbey JL, Clements JD, Kirk K. The ‘permeome’ of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum. Genome Biol. 2005; 6:R26.
Roberts F, Roberts CW, Johnson JJ, et al. Evidence for shikimate pathway in apicomplexan parasites. Nature.1998; 393:801.
Jomaa H, Jochen W, Sanderbrand S, et al. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science.1999; 285:1573.
Doerig C, Endicott J, Chakrabarti D. Cyclin-dependent kinase homologues of Plasmodium falciparum. Int J Parasitol. 2002; 32:1575.
[a]. Blackman M. Proteases involved in erythrocyte invasion by the malaria parasite: function and potential as chemotherapeutic targets. Curr Drug Targets. 2000; 1:59.
[b]. Coteron M. jose, et al. Falcipian Inhibitors: Optimization Studies of the 2-Pyrimidinecarbonitrile Lead Series. Jounral of Medicinal Chemistry . 2010.
Salmon BL, Oksman A, Goldberg DE. Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis. Proc Natl Acad Sci USA. 2000; 98:271.
Bailly E, Jambou R, Savel J, Jaureguiberry G. Plasmodium falciparum: differential sensitivity in vitro to E-64 (cysteine protease inhibitor) and Pepstatin A (aspartyl protease inhibitor). J Protozool. 1992; 39: 593.
Singh A, Rosenthal PJ. Comparison of efficacies of cysteine protease inhibitors against five strains of Plasmodium falciparum. Antimicrob Agents Chemother. 2001; 45:949.
Pandey KC, Wang SX, Sijwali PS, Lau AL, McKerrow JH, Rosenthal PJ. The Plasmodium falciparum cysteine protease Falcipian-2 captures its substrate, hemoglobin, via a unique motif. Proc Natl Acad Sci USA. 2005; 102:9138.
Rosenthal PJ, Olson JE, Lee GK, Palmer JT, Klaus JL, Rasnick D. Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. Antimicrob Agents Chemother. 1996; 40:1600.
Lee BJ, Singh A, Chiang P, et al. Antimalarial activities of novel synthetic cysteine protease inhibitors. Antimicrob Agents Chemother. 2003; 47:3810.
Barrett AJ, Rawlings ND. Evolutionary lines of cysteine peptidases. Biol. Chem. 2001; 382: 727.
Barrett AJ, Rawlings ND, Woessner JF. Handbook of Proteolytic Enzymes. Academic Press, San Diego, CA.1998.
Turk V, Turk B, Turk D. Lysosomal cysteine proteases: facts and opportunities. Eur. Mol. Biol. Org. J. 2001; 20: 4629.
Wu Y, Wang X, Liu X, Wang Y. Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite. Genome Res. 2003; 13: 601.
Rosenthal PJ. Protease inhibitors, in: Rosenthal PJ (Ed.), Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Humana Press, Totowa, NJ, 2001: 325.
Shenai BR, Rosenthal PJ. Reducing requirements for hemoglobin hydrolysis by Plasmodium falciparum cysteine proteases. Mol. Biochem. Parasitol. 2002; 122:99.
Francis SE, Sullivan Jr DJ, Goldberg DE. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol.1997b: 51: 97.
McKerrow JH, Sun E, Rosenthal PJ, Bouvier J. The proteases and pathogenicity of parasitic protozoa. Annu. Rev. Microbiol.1993; 47: 821.
Lew VL, Tiffert T, Ginsburg H. Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells. Blood2003; 101: 4189.
Bailly E, Jambou R, Savel J, Jaureguiberry G. Plasmodium falciparum: differential sensitivity in vitro to E-64 (cysteine protease inhibitor) and Pepstatin A (aspartyl protease inhibitor). J. Protozool. 1992; 39:593.
Dluzewski AR, Rangachari K, Wilson RJ, Gratzer WB. Plasmodium falciparum: protease inhibitors and inhibition of erythrocyte invasion. Exp. Parasitol.1986; 62: 416.
Rosenthal PJ, McKerrow JH, Aikawa M, Nagasawa H, Leech JH. A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum. J. Clin. Invest.1988; 82: 1560.
Gluzman IY, Francis SE, Oksman A, Smith CE, Duffin KL, Goldberg DE. Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. J. Clin. Invest. 1994; 93: 1602.
Rosenthal PJ. Plasmodium falciparum: effects of proteinase inhibitors on globin hydrolysis by cultured malaria parasites. Exp. Parasitol. 1995; 80: 272.
Gamboa de Dominguez ND, Rosenthal PJ. Cysteine proteinase inhibitors block early steps in hemoglobin degradation by cultured malaria parasites. Blood.1996; 87: 4448.
Francis SE, Banerjee R, Goldberg DE. Biosynthesis and maturation of the malaria aspartic hemoglobinases plasmepsins I and II. J. Biol. Chem. 1997a; 272: 14961.
Debrabant A, Delplace P. Leupeptin alters the proteolytic processing of P126, the major parasitophorous vacuole antigen of Plasmodium falciparum. Mol. Biochem. Parasitol.1989; 33: 151.
Hadley T, Aikawa M, Miller LH. Plasmodium knowlesi: studies on invasion of rhesus erythrocytes by merozoites in the presence of protease inhibitors. Exp. Parasitol.1983; 55: 306.
Lyon JA, Haynes JD, Diggs CL, Chulay JD, Pratt-Rossiter JM. Plasmodium falciparum antigens synthesised by schizonts and stabilised at the merozoite surface by antibodies when schizonts mature in the presence of growth inhibitory immune serum. J. Immunol.1986; 136: 2252.
Salmon BL, Oksman A, Goldberg DE. Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis. Proc. Natl Acad. Sci. USA.2001: 98: 271.
Wickham ME, Culvenor JG, Cowman AF. Selective inhibition of a two-step egress of malaria parasites from the host erythrocyte. J. Biol. Chem.2003; 278: 37658.
Rosenthal PJ. Protease inhibitors, in: Rosenthal PJ (Ed.), Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery. Humana Press, Totowa, NJ. 2001 pp. 325.
Breton CB, Blisnick T, Jouin H, Barale JC, Rabilloud T, Langsley G, Pereira da Silva LH. Plasmodium chabaudi p68 serine protease activity required for merozoite entry into mouse erythrocytes. Proc. Natl Acad. Sci. USA. 1992; 89: 9647.
Hadley T, Aikawa M, Miller LH. Plasmodium knowlesi: studies on invasion of rhesus erythrocytes by merozoites in the presence of protease inhibitors. Exp. Parasitol. 1983; 55: 306.
Greenbaum DC, Baruch A, Grainger M, Bozdech Z, Medzihradszky KF, Engel J, DeRisi J, Holder AA, Bogyo M. A role for the protease Falcipian 1 in host cell invasion by the human malaria parasite. Science.2002; 298: 2002.
Williamson KC, Fujioka H, Aikawa M, Kaslow DC. Stage-- specific processing of Pfs230, a Plasmodium falciparum transmission blocking vaccine candidate. Mol. Biochem. Parasitol.1996; 78: 161.
Brooks SR, Williamson KC. Proteolysis of Plasmodium falciparum surface antigen, Pfs230, during gametogenesis. Mol. Biochem. Parasitol.2000; 106: 77.
Eksi S, Czesny B, Greenbaum DC, Bogyo M, Williamson KC . Targeted disruption of Plasmodium falciparum cysteine protease, Falcipian 1, reduces oocyste production, not erythrocyte stage growth. Mol. Microbiol.2004; 53: 243.
Chiyanzu I, Elizabeth H, Jiri G, Rosethal PJ, Mckerrow J, Chibale K. Synthesis and evaluation of isatins and thiosemicarbazone derivatives against Cruzain, Falcipian-2, and Rhodesain. Bioorg. Med. Chem. Lett. 2003; 13: 3527.
Greenbaum DC, Mackey Z, Hansell E, Doyle, P, Gut, J, Caffrey C R, Lehrman J, Rosenthal P J, Mckerrow J, Chibale K. Synthesis and SAR of parasiticidal thiosemicarbazone Cysteine Protease inhibitors against Plasmodium Falciparum, T. Brucei, T. Cruzi. J. Med. Chem. 2004; 47: 3212.
Rosenthal P J, Dahl EL. Biosynthesis, localization and processing of Falcipian cysteine proteases of Plasmodium falciparum. Molecular & Biochemical Parasitology, 2005; 139: 205.
Chiyanzu I, Clarkson C, Smith PJ, Lehman J, Gut J, Rosenthal PJ, Chibale K. Design Synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinazoline isatin derivatives. Bioorg. & Med. Chem. 2005; 13: 3249.
Dominguez JN, Leon C, Rodrigues J, Gut J, Rosenthal PJ. Synthesis and Evaluation of new antimalarial phenylurenyl chalcone derivatives. J. Med. Chem. 2005; 48: 3654.
Valente C, Guedes RC, Moreira R, Iley J, Gut J, Rosenthal PJ. Dipeptide vinyl sultams: Synthesis via the Wittig-Horner reaction and activity against papain, Falcipian-2 and Plasmodium falciparum. Bioorg. & Med. Chem. Lett. 2006; 16: 4115.
Chipeleme A, Gut J, Rosenthal PJ, Chibale K. Synthesis and biological evaluation of phenolic Mannich bases of benzaldehyde and thiosemicarbazone derivatives against the cysteine protease Falcipian-2 and a chloroquine resistant strain of Plasmodium falciparum. Bioorg. & Med. Chem.2007; 15: 273.
Verissimo E, Berry N, Gibbons P, Cristiano MLS, Rosenthal PJ, Gut J, Ward SA, O’Neill PM. Design and synthesis of novel 2-pyridone peptidometic Falcipian 2/3 inhibitors. Bioorg. &Med. Chem. Lett. 2008; 18: 4210.
Loser R, Gut J, Rosenthal PJ, Frizler M, Gutschow M, Andrews KT. Antimalarial activity of azadipeptide nitriles. Bioorg. &Med. Chem. Lett. 2010; 20: 252.
Hans RH, Guantai EM, Lategan C, Smith PJ, Wan B, Franzblau SG, Gut J, Rosenthal PJ, Chibale K. Synthesis, antimalarial and anti tubercular activity of acetylenic chalcones. Bioorg. & Med. Chem. Lett. 2010; 20: 942.
Kerr ID, Lee JH, Pandey KC, Harrison A, Sajid M, Rosenthal PJ, Brinen LS. Structures of Falcipian-2 and Falcipian-3 Bound to Small molecule Inhibitors: Implications for Substrate Specificity. J. Med. Chem. 2009; 52, 852.
Sijwali PS, Shenai BR, Gut J, Singh A, Rosenthal PJ. Expression and characterization of the Plasmodium falciparum haemoglobinase Falcipian-3. Biochem. J. 2001b; 360:481.
Rosenthal PJ. Cysteine poteases of malaria parasite. Int. J. of Parasitol. 2004; 34:1489.
Garcia LGE, Rodriguez JB. Current status and progress made in malaria chemotherapy. Curr. Med. Chem. 2007; 14: 289.
Goldberg DE. Semin. Cell Biol. Hemoglobin degradation in Plasmodium infected red blood cells.1993; 4: 355.
Rosenthal PJ. Cysteine proteases of malaria parasites.Int. J. Parasitol. 2004; 34: 1489.
Ersmark K, Samuelson B, Hallberg A.Plasmepsins as potential targets for new antimalarial therapy. Med. Res. Rev. 2006; 26: 626.
Rosenthal PJ, Sijwali P S, Singh A., Shenai BR. Cysteine proteases of malaria parasite: targets for chemotherapy. Curr. Pharm. Des. 2002, 8: 1659.
Hansch, C.; Leo, A.; Substituent Constants for Correlation Analysis in Chemistry and Biology, John Wiley & Sons, New York, 1979.
Livingstone, DJ. Perspective: “The charactarization of chemical structure using molecular properties. A Survey”. J. Chem. Inf. Comput. Sci.2000; 40: 195.
Hansch C, Kurup A, Garg R, Gao H. A review of QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP lacking positive hydrophobic termsChem. Rev.2001; 101: 619.
Crum-Brown A, Fraser TR. On the connection between chemical constitution and physiological action. Part1. On the physiological action of the ammonium bases, derived from Strychia, Brucia, Thebaia, Codeia, Morphia and Nicotia. Trans. R. Soc. Edinburgh. 1868; 25: 151.
Richet C, Seancs C R. Comptes Rendus des Seances de la Societe de Biologie et de ses Filiales. Soc. Biol. Ses. Fil.1893; 9: 775.
Meyer H. “Welche eigenschaft der anaesthetica bedingt inre Narkotische wirkung?” Arch. Exp. Pathol. Pharmakol.1899; 42: 109.
Overton, E.; Studien Uber die Narkose, Fischer, Jena, Germany, 1901.
Ferguson J. The use of chemical potential as indices of toxicity. Proc. R. Soc. London Ser. B.1939; 127: 387-404.
Hammett LP. Chem. Rev.1935; 17: 125.
Hammett LP. ‘Physical Organic Chemistry’, 2nd ed., McGraw-Hill, New York, 1970.
Taft RW. J. Am. Chem. Soc.1952; 74: 3120.
Guner OF. Pharmacophore perception, development, and use in drug design. International University Line, La Jolla, CA.2000.
Van Drie JH. Pharmacophor discovery- lessons learned. Curr Pharm Design. 2003; 9:1649.
Topliss JG. Quantitative structure-activity relationships of drugs, Vol 19. Academic Press, New York. 1983.
Martin YC. Quantitative drug design: a critical introduction. Marcel Dekker, New York.1978.
Hansch C, Fujita T. J Am Chem Soc. 1964; 86:1616.
Gund P, Wipke WT, Langridge R. Computer searching of a molecular structure file for pharmacophoric patterns. Elsevier, Amsterdam. 1974, 3: 33.
Kier LB, Hall LH .Molecular connectivity in chemistry and drug research. Academic Press, London. 1976.
Hancsh C, Leo A. Substituent constants for correlation analysis in chemistry and biology. Wiley, New York. 1979.
Hopfinger AJ. A QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP investigation of dihydrofolate reductase inhibition by Baker triazines based upon molecular shape analysis. J Am Chem Soc. 1980;102:7196.
Van Drie JH, Weininger D, Martin YC. ALADDIN: an integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric, and substructure searching of 3-D molecular structures. J Comput- Aided Mol Design.1989; 3:225.
Lauri G, Bartlett PA. CAVEAT: A program to facilitate design of organic molecules. J Comput-Aided Mol Design. 1994; 8:51.
Van Drie JH. Strategies for the determination of pharmacophoric 3D database queries. J Comput-Aided Mol Design. 1997; 11:39.
Chen X, Rusinko A, III Young SS. Recursive partitioning analysis of a large structure-activity data set using 3-D descriptors. J Chem Inf Comput Sci .1998;38:1054.
Chen X, Rusinki A, III Tropsha A, Young SS. J Chem Inf Comput Sci.1999; 39:887.
Greene J, Kahn S, Savoj H, Sprague P, Teig S. J Chem Inf Comput Sci .1994;34:1297.
Barnum D, Greene J, Smellie A, Sprague P. Identification of common functional configuration among molecules. J Chem Inf Comput Sci.1996; 36:563.
Martin YC, In Hansch C, Fujita T. Classical and 3D QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP in agrochemistry. American Chemical Society, Washington, DC. 1995; 318.
Jones G, Willett P, Glen RC. A genetic algorithm for flexible molecular overlay and pharmacophore elucidation. J Comput-Aided Mol Design. 1995; 9:532.
Cramer RD, Patterson DE, Bunce JD. COMFA: Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc. 1988; 110:5959.
Van Drie JH, In Guner OF .Pharmacophore perception, development, and use in drug design. International University Line, La Jolla, CA. 2000; 517–530.
Phase, version 3.1, Schrodinger, LLC. New York, NY, 2009.
Lengauer T, Rarey M. "Computational methods for biomolecular docking". Curr. Opin. Struct. Biol. 1996;6 (3): 402.
Shoichet BK, Kuntz ID, Bodian DL. "Molecular docking using shape descriptors". Journal of Computational Chemistry .2004;13 (3): 380.
Cai W, Shao X, Maigret B. "Protein-ligand recognition using spherical harmonic molecular surfaces: towards a fast and efficient filter for large virtual throughput screening". J. Mol. Graph. Model. 2002;20 (4): 313.
Morris RJ, Najmanovich RJ, Kahraman A, Thornton JM. "Real spherical harmonic expansion coefficients as 3D shape descriptors for protein binding pocket and ligand comparisons". Bioinformatics. 2005;21 (10): 2347.
Kahraman A, Morris RJ, Laskowski RA, Thornton JM. "Shape variation in protein binding pockets and their ligands". J. Mol. Biol. 2007; 368 (1): 283.
Suresh PS, Kumar A, Kumar R, Singh VP. "An in silico [correction of insilico] approach to bioremediation: laccase as a case study".J. Mol. Graph. Model. 2008; 26 (5): 845.
Chipeleme A, Gut G, Rosenthal PJ, Chibale K. Synthesis and biological evaluation of phenolic Mannich bases of benzaldehyde and thiosemicarbazone derivative against the cysteine protease Falcipian2 and a chloroquine resistant strain of P. falciparum. Bioorg. & Med. Chem. 2007; 15: 273.
Chiyanzu I, Gut J, Rosenthal PJ, Chibale K. Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, Falcipian2 and Rhodesain. Bioorg. & Med. Chem. Lett. 2003; 13: 3527.
Dominguez JN, Leon C. Synthesis and evaluation of new antimalarials Phenyl urenyl chalcone derivative. J. Med. Chem. 2005; 48: 3654.
Gut J, Rosenthal PJ. Falcipian inhibitors: optimization studies of the 2- pyrimidino carbonitrile lead series. J. Med. Chem. 2010.
Gund P. In Pharmacophore Perception, Development, and Drug Design; Gunner, O. F., Ed.; International University Line: La Jolla,CA, 2000; 3.
Smellie A, Teig SL, Poling TP. Promoting Conformational Variation. J. Comput. Chem. 1995; 16: 171.
Published
How to Cite
Issue
Section
Copyright (c) 2023 Tropical Journal of Pharmaceutical and Life Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.