In silico prediction and in vitro assessment of novel heterocyclics with antimalarial activity.
Antimalarial susceptibility
Heterocyclics
Plasmodium falciparum
Journal
Parasitology research
ISSN: 1432-1955
Titre abrégé: Parasitol Res
Pays: Germany
ID NLM: 8703571
Informations de publication
Date de publication:
29 Dec 2023
29 Dec 2023
Historique:
received:
03
09
2023
accepted:
05
12
2023
medline:
29
12
2023
pubmed:
29
12
2023
entrez:
28
12
2023
Statut:
epublish
Résumé
The development of new antimalarials is paramount to keep the goals on reduction of malaria cases in endemic regions. The search for quality hits has been challenging as many inhibitory molecules may not progress to the next development stage. The aim of this work was to screen an in-house library of heterocyclic compounds (HCUV) for antimalarial activity combining computational predictions and phenotypic techniques to find quality hits. The physicochemical determinants, pharmacokinetic properties (ADME), and drug-likeness of HCUV were evaluated in silico, and compounds were selected for structure-based virtual screening and in vitro analysis. Seven Plasmodium target proteins were selected from the DrugBank Database, and ligands and receptors were processed using UCSF Chimera and Open Babel before being subjected to docking using Autodock Vina and Autodock 4. Growth inhibition of P. falciparum (3D7) cultures was tested by SYBR Green assays, and toxicity was assessed using hemolytic activity tests and the Galleria mellonella in vivo model. From a total of 792 compounds, 341 with good ADME properties, drug-likeness, and no interference structures were subjected to in vitro analysis. Eight compounds showed IC
Identifiants
pubmed: 38155300
doi: 10.1007/s00436-023-08089-7
pii: 10.1007/s00436-023-08089-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
75Subventions
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Organisme : Universidad del Valle
ID : Internal Grant Scheme 1907, 2020
Informations de copyright
© 2023. The Author(s).
Références
Acharya B, Saraswat D, Tiwari M, Kumar A (2010) Synthesis and antimalarial evaluation of 1, 3, 5-trisubstituted pyrazolines. Eur J Med Chem 45:430–438. https://doi.org/10.1016/j.ejmech.2009.10.023
doi: 10.1016/j.ejmech.2009.10.023
pubmed: 19926176
Allegra E, Titball RW, Carter J, Champion OL (2018) Galleria mellonella larvae allow the discrimination of toxic and non-toxic chemicals. Chemosphere 198:469–472. https://doi.org/10.1101/2021.07.06.451318
doi: 10.1101/2021.07.06.451318
pubmed: 29425947
Banerjee P, Eckert AO, Schrey AK, Preissner R (2018) ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 46:W257–W263. https://doi.org/10.1093/nar/gky318
doi: 10.1093/nar/gky318
pubmed: 29718510
pmcid: 6031011
Bekhit AA, Hymete A, Damtew A, Mohamed AMI, Bekhit AEDA (2012) Synthesis and biological screening of some pyridine derivatives as anti-malarial agents. J Enzyme Inhib Med Chem 27:69–77. https://doi.org/10.3109/14756366.2011.575071
doi: 10.3109/14756366.2011.575071
pubmed: 21612373
Bentzinger G, Pair E, Guillon J, Marchivie M, Mullié C, Agnamey P, Dassonville-Klimpt A, Sonnet P (2020) Enantiopure substituted pyridines as promising antimalarial drug candidates. Tetrahedron 76:1–12. https://doi.org/10.1016/j.tet.2020.131088
doi: 10.1016/j.tet.2020.131088
Bhojwani HR, Joshi UJ (2019) Selecting protein structure/s for docking-based virtual screening: a case study on type II inhibitors of Vegfr-2 kinase. Int J Pharm Sci Res 10:2998–3011. https://doi.org/10.13040/IJPSR.0975-8232
doi: 10.13040/IJPSR.0975-8232
Burger PB, Williams M, Sprenger J, Reeksting SB, Botha M, Müller IB, Joubert F, Birkholtz LM, Louw AI (2015) A novel inhibitor of Plasmodium falciparum spermidine synthase: a twist in the tail. Malar J 14:1–18. https://doi.org/10.1186/s12936-015-0572-z
doi: 10.1186/s12936-015-0572-z
Butt SS, Badshah Y, Shabbir M, Rafiq M (2020) Molecular docking using chimera and Autodock Vina software for non bioinformaticians. JMIR Bioinforma Biotechnol 1:e14232. https://doi.org/10.2196/14232
doi: 10.2196/14232
Corbett KD, Berger JM (2010) Structure of the ATP-binding domain of Plasmodium falciparum Hsp90. Proteins Struct Funct Bioinforma 78:2738–2744. https://doi.org/10.1002/prot.22799
doi: 10.1002/prot.22799
Cuartas V, Robledo SM, Vélez ID, Crespo MP, Sortino M, Zacchino S, Nogueras M, Cobo J, Upegui Y, Pineda T et al (2020) New thiazolyl-pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents. Arch Pharm (Weinheim) 353:5. https://doi.org/10.1002/ardp.201900351
doi: 10.1002/ardp.201900351
Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:1–13. https://doi.org/10.1038/srep42717
doi: 10.1038/srep42717
Dhameliya TM, Kathuri D, Patel TM, Dave BP, Chaudhari AZ, Vekariya DD (2023) A quinquennial review on recent advancements and developments in search of anti-malarial agents. Curr Top Med Chem 23:753–790. https://doi.org/10.2174/1568026623666230427115241
doi: 10.2174/1568026623666230427115241
pubmed: 37102486
Dutta T, Singh H, Edkins AL, Blatch GL (2022) Hsp90 and associated co-chaperones of the malaria parasite. Biomolecules 12:1–16. https://doi.org/10.3390/biom12081018
doi: 10.3390/biom12081018
Eagon S, Hammill JT, Sigal M, Ahn KJ, Tryhorn JE, Koch G, Belanger B, Chaplan CA, Loop L, Kashtanova AS et al (2020) Synthesis and structure-activity relationship of dual-stage antimalarial pyrazolo[3,4- b]pyridines. J Med Chem 63:11902–11919. https://doi.org/10.1021/acs.jmedchem.0c01152
doi: 10.1021/acs.jmedchem.0c01152
pubmed: 32945666
Egan WJ, Merz KM, Baldwin JJ (2000) Prediction of drug absorption using multivariate statistics. J Med Chem 43:3867–3877. https://doi.org/10.1021/jm000292e
doi: 10.1021/jm000292e
pubmed: 11052792
Ekawati L, Nurohmah BA, Syahri J, Purwono B (2022) Substituted 3-styryl-2-pyrazoline derivatives as an antimalaria: synthesis, in vitro assay, molecular docking, druglikeness analysis, and ADMET prediction. Sains Malaysiana 51:3215–3236. https://doi.org/10.17576/jsm-2022-5110-09
doi: 10.17576/jsm-2022-5110-09
Ertl P, Schuffenhauer A (2009) Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. J Cheminform 1:1–11. https://doi.org/10.1186/1758-2946-1-8
doi: 10.1186/1758-2946-1-8
Fährrolfes R, Bietz S, Flachsenberg F, Meyder A, Nittinger E, Otto T, Volkamer A, Rarey M (2017) Proteins Plus: a web portal for structure analysis of macromolecules. Nucleic Acids Res 45:W337–W343. https://doi.org/10.1093/nar/gkx333
doi: 10.1093/nar/gkx333
pubmed: 28472372
pmcid: 5570178
Fatimawali, Tallei TE, Kepel BJ, Alorabi M, El-Shehawi AM, Bodhi W, Tumilaar SG, Celik I, Mostafa-Hedeab G, Mohamed AAR et al. (2021) Appraisal of bioactive compounds of betel fruit as antimalarial agents by targeting plasmepsin 1 and 2: a computational approach. Pharmaceuticals. 14. https://doi.org/10.3390/ph14121285 .
Frasse PM, Odom J, Audrey R (2019) Haloacid dehalogenase proteins: novel mediators of metabolic plasticity in Plasmodium falciparum. Microbiol Insights 12:117863611984843. https://doi.org/10.1177/1178636119848435
doi: 10.1177/1178636119848435
Ghose AK, Viswanadhan VN, Wendoloski JJ (1999) A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1:55–68. https://doi.org/10.1021/cc9800071
doi: 10.1021/cc9800071
pubmed: 10746014
Gore S, Sanz García E, Hendrickx PMS, Gutmanas A, Westbrook JD, Yang H, Feng Z, Baskaran K, Berrisford JM, Hudson BP et al (2017) Validation of structures in the Protein Data Bank. Structure 25:1916–1927. https://doi.org/10.1016/j.str.2017.10.009
doi: 10.1016/j.str.2017.10.009
pubmed: 29174494
pmcid: 5718880
Green JL, Moon RW, Whalley D, Bowyer PW, Wallace C, Rochani A, Nageshan RK, Howell SA, Grainger M, Jones HM et al (2016) Imidazopyridazine inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 also target cyclic GMP-dependent protein kinase and heat shock protein 90 to kill the parasite at different stages of intracellular development. Antimicrob Agents Chemother 60:1464–1475. https://doi.org/10.1128/AAC.01748-15
doi: 10.1128/AAC.01748-15
pmcid: 4775997
Guggisberg AM, Park J, Edwards RL, Kelly ML, Hodge DM, Tolia NH, Odom AR (2014) A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites. Nat Commun. https://doi.org/10.1128/mbio.01193-18
doi: 10.1128/mbio.01193-18
pubmed: 25058848
Guggisberg AM, Frasse PM, Jezewski AJ, Kafai NM, Gandhi AY, Erlinger SJ, John ARO (2018) Suppression of drug resistance reveals a genetic mechanism of metabolic plasticity in malaria parasites. Mbio 9:1–16. https://doi.org/10.1038/ncomms5467
doi: 10.1038/ncomms5467
Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek EHG (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:17. https://doi.org/10.1186/1758-2946-4-17
doi: 10.1186/1758-2946-4-17
pubmed: 22889332
pmcid: 3542060
Kamil M, Kina UY, Deveci G, Akyuz SN, Yilmaz I, Aly ASI (2022) Mitochondrial Spermidine Synthase is essential for blood-stage growth of the malaria parasite. Microbiol Res 265:127181. https://doi.org/10.1016/j.micres.2022.127181
doi: 10.1016/j.micres.2022.127181
pubmed: 36162149
Kato N, March S, Bhatia SN and Marti M (2018) Phenotypic screening of small molecules with antimalarial activity for three different parasitic life stages. In: Wagner B (ed) Phenotypic Screening. Methods in Molecular Biology. Human Press, New York, NY, pp 41–52. https://doi.org/10.1007/978-1-4939-7847-2_3 .
Kimura R, Komaki-Yasuda K, Kawazu S, Kano S (2013) 2-Cys peroxiredoxin of Plasmodium falciparum is involved in resistance to heat stress of the parasite. Parasitol Int 62:137–143. https://doi.org/10.1016/j.parint.2012.11.005
doi: 10.1016/j.parint.2012.11.005
pubmed: 23201565
Kokkonda S, Deng X, White KL, Coteron JM, Marco M, De Las HL, White J, El Mazouni F, Tomchick DR, Manjalanagara K et al (2016) Tetrahydro-2-naphthyl and 2-Indanyl triazolopyrimidines targeting Plasmodium falciparum dihydroorotate dehydrogenase display potent and selective antimalarial activity. J Med Chem 59:5416–5431. https://doi.org/10.1021/acs.jmedchem.6b00275
doi: 10.1021/acs.jmedchem.6b00275
pubmed: 27127993
pmcid: 4904246
Kumar P, Kadyan K, Duhan M, Sindhu J, Singh V, Saharan BS (2017) Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents. Chem Cent J 11:1–14. https://doi.org/10.1186/s13065-017-0344-7
doi: 10.1186/s13065-017-0344-7
Kumar S, Haile MT, Hoopmann MR, Tran LT, Michaels SAMS, Ojo KK, Reynolds LM, Kusebauch U, Vaughan AM, Moritz RLKS, Swearingen KE (2021) Plasmodium falciparum calcium-dependent protein kinase 4 is critical for male gametogenesis and transmission to the mosquito vector. Mbio 12:e02575-e2621
doi: 10.1128/mBio.02575-21
pubmed: 34724830
pmcid: 8561384
Le Manach C, Paquet T, Brunschwig C, Njoroge M, Han Z, Gonzàlez Cabrera D, Bashyam S, Dhinakaran R, Taylor D, Reader J et al (2015) A novel pyrazolopyridine with in vivo activity in Plasmodium berghei- and Plasmodium falciparum-infected mouse models from structure-activity relationship studies around the core of recently identified antimalarial imidazopyridazines. J Med Chem 58:8713–8722. https://doi.org/10.1021/acs.jmedchem.5b01605
doi: 10.1021/acs.jmedchem.5b01605
pubmed: 26502160
Ling Y, Hao ZY, Liang D, Zhang CL, Liu YF, Wang Y (2021) The expanding role of pyridine and dihydropyridine scaffolds in drug design. Drug Des Devel Ther 15:4289–4338. https://doi.org/10.2147/DDDT.S329547
doi: 10.2147/DDDT.S329547
pubmed: 34675489
pmcid: 8520849
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 64:4–17. https://doi.org/10.1016/j.addr.2012.09.019
doi: 10.1016/j.addr.2012.09.019
Liu J, Gluzman IY, Drew ME, Goldberg DE (2005) The role of Plasmodium falciparum food vacuole plasmepsins. J Biol Chem 280:1432–1437. https://doi.org/10.1074/jbc.M409740200
doi: 10.1074/jbc.M409740200
pubmed: 15513918
Liu J, Istvan ES, Goldberg DE (2006) Hemoglobin-degrading plasmepsin II is active as a monomer. J Biol Chem 281:38682–38688. https://doi.org/10.1074/jbc.M608535200
doi: 10.1074/jbc.M608535200
pubmed: 17040901
Madrid DC, Ting LM, Waller KL, Schramm VL, Kim K (2008) Plasmodium falciparum purine nucleoside phosphorylase is critical for viability of malaria parasites. J Biol Chem 283:35899–35907. https://doi.org/10.1074/jbc.M807218200
doi: 10.1074/jbc.M807218200
pubmed: 18957439
pmcid: 2602904
Mahapatra RK, Das M (2020) A computational approach to validate novel drug targets of gentianine from Swertiya chirayita in Plasmodium falciparum. BioSystems 196:104175. https://doi.org/10.1016/j.biosystems.2020.104175
doi: 10.1016/j.biosystems.2020.104175
pubmed: 32593550
Manhas A, Kumar S, Jha PC (2022) Identification of the natural compound inhibitors against Plasmodium falciparum plasmepsin-II via common feature based screening and molecular dynamics simulations. J Biomol Struct Dyn 40:31–43. https://doi.org/10.1080/07391102.2020.1806110
doi: 10.1080/07391102.2020.1806110
pubmed: 32794426
Martin YC (2005) A bioavailability score. J Med Chem 48:3164–3170. https://doi.org/10.1021/jm0492002
doi: 10.1021/jm0492002
pubmed: 15857122
Meanwell NA and Walker MA (2008) 13.06 - 1,4-Diazepines. Compr Heterocycl Chem III Bristol-Myers Squibb Research and Development, Wallingford, CT, USA 13, pp. 183–235
Mishra VK, Mishra M, Kashaw V, Kashaw SK (2017) Synthesis of 1,3,5-trisubstituted pyrazolines as potential antimalarial and antimicrobial agents. Bioorganic Med Chem 25:1949–1962. https://doi.org/10.1016/j.bmc.2017.02.025
doi: 10.1016/j.bmc.2017.02.025
Moll K, Kaneko A, Scherf A, Wahlgren M (2013) Methods in Malaria Research, 6th ed. EviMalaR, Glasgow, UK & MR4/ATCC, Manassas, VA, USA
Muegge I, Heald SL and Brittelli D (2001) Simple selection criteria for drug-like chemical matter. J Med Chem 44. https://doi.org/10.1021/jm015507e
O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR (2011) Open Babel. J Cheminform 3:1–14. https://doi.org/10.1186/1758-2946-3-33
doi: 10.1186/1758-2946-3-33
Pandey AK, Sharma S, Pandey M, Alam MM, Shaquiquzzaman M, Akhter M (2016) 4, 5-Dihydrooxazole-pyrazoline hybrids: synthesis and their evaluation as potential antimalarial agents. Eur J Med Chem 123:476–486. https://doi.org/10.1016/j.ejmech.2016.07.055
doi: 10.1016/j.ejmech.2016.07.055
pubmed: 27494165
Park J, Guggisberg AM, Odom AR, Tolia NH (2015) Cap-domain closure enables diverse substrate recognition by the C2-type haloacid dehalogenase-like sugar phosphatase Plasmodium falciparum HAD1. Acta Crystallogr Sect D Biol Crystallogr 71:1824–1834. https://doi.org/10.1107/S1399004715012067
doi: 10.1107/S1399004715012067
Piatek M, Sheehan G, Kavanagh K (2021) Galleria mellonella: the versatile host for drug discovery, in vivo toxicity testing and characterising host-pathogen interactions. Antibiotics. https://doi.org/10.3390/antibiotics10121545
doi: 10.3390/antibiotics10121545
pubmed: 34943757
pmcid: 8698334
Ramírez-Prada J, Robledo SM, Vélez ID, del Crespo M, P, Quiroga J, Abonia R, Montoya A, Svetaz L, Zacchino S and Insuasty B, (2017) Synthesis of novel quinoline–based 4,5–dihydro–1H–pyrazoles as potential anticancer, antifungal, antibacterial and antiprotozoal agents. Eur J Med Chem 131:237–254. https://doi.org/10.1016/J.EJMECH.2017.03.016
doi: 10.1016/J.EJMECH.2017.03.016
pubmed: 28329730
Rathod GK, Jain M, Sharma KK, Das S, Basak A, Jain R (2022) New structural classes of antimalarials. Eur J Med Chem 242:114653. https://doi.org/10.1016/j.ejmech.2022.114653
doi: 10.1016/j.ejmech.2022.114653
pubmed: 35985254
Ravindar L, Hasbullah SA, Rakesh KP, Hassan NI (2023) Pyrazole and pyrazoline derivatives as antimalarial agents: a key review. Eur J Pharm Sci 183:106365. https://doi.org/10.1016/j.ejps.2022.106365
doi: 10.1016/j.ejps.2022.106365
pubmed: 36563914
Recacha R, Leitans J, Akopjana I, Aprupe L, Trapencieris P, Jaudzems K, Jirgensons A, Tars K (2015) Structures of plasmepsin II from Plasmodium falciparum in complex with two hydroxyethylamine-based inhibitors. Acta Crystallogr Sect Struct Biol Commun 71:1531–1539. https://doi.org/10.1107/S2053230X15022049
doi: 10.1107/S2053230X15022049
Rodrigues T, Guedes RC, dos Santos DJVA, Carrasco M, Gut J, Rosenthal PJ, Moreira R, Lopes F (2009) Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials. Bioorganic Med Chem Lett 19:3476–3480. https://doi.org/10.1016/j.bmcl.2009.05.017
doi: 10.1016/j.bmcl.2009.05.017
Shahinas D, Folefoc A, Taldone T, Chiosis G, Crandall I, Pillai DR (2013) A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium falciparum Hsp90 (PfHsp90). PLoS ONE. https://doi.org/10.1371/journal.pone.0075446
doi: 10.1371/journal.pone.0075446
pubmed: 24098696
pmcid: 3787104
Sharma PP, Sethi A, Diwedi B, Grishina M, Rathi B, Singh G (2022) Novel inhibitors of malarial aspartyl proteases, plasmepsin II and IV: in silico design and validation studies. Chem Biol Lett 9:315
Silva AM, Lee AY, Gulnik SV, Majer P, Collins J, Bhat TN, Collins PJ, Cachau RE, Luker KE, Gluzman IY et al (1996) Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum. Proc Natl Acad Sci U S A 93:10034–10039. https://doi.org/10.1073/pnas.93.19.10034
doi: 10.1073/pnas.93.19.10034
pubmed: 8816746
pmcid: 38331
Silva TB, Bernardino AMR, Ferreira M de LG, Rogerio KR, Carvalho LJM, Boechat N, Pinheiro LCS (2016) Design, synthesis and anti-P. falciparum activity of pyrazolopyridine–sulfonamide derivatives. Bioorganic Med Chem 24:4492–4498. https://doi.org/10.1016/j.bmc.2016.07.049
doi: 10.1016/j.bmc.2016.07.049
Sousa AP, Oliveira MS, Fernandes DA, Ferreira MDL, Cordeiro LV, Souza MFV, Fernandes LMD, Souza HDS, Oliveira Filho AA, Pessoa HLF et al (2021) In silico, in vitro, and ex vivo studies of the toxicological and pharmacological properties of the flavonoid 5,7-dihydroxy-3,8,4’-trimethoxy. Brazilian J Med Biol Res 54:4–9. https://doi.org/10.1590/1414-431X2021E11203
doi: 10.1590/1414-431X2021E11203
Staudacher V, Djuika CF, Koduka J, Schlossarek S, Kopp J, Büchler M, Lanzer M, Deponte M (2015) Plasmodium falciparum antioxidant protein reveals a novel mechanism for balancing turnover and inactivation of peroxiredoxins. Free Radic Biol Med 85:228–236. https://doi.org/10.1016/j.freeradbiomed.2015.04.030
doi: 10.1016/j.freeradbiomed.2015.04.030
pubmed: 25952724
Stofberg ML, Caillet C, de Villiers M, Zininga T (2021) Inhibitors of the Plasmodium falciparum hsp90 towards selective antimalarial drug design: the past, present and future. Cells. https://doi.org/10.3390/cells10112849
doi: 10.3390/cells10112849
pubmed: 34831072
pmcid: 8616389
Swearingen KE (2012) Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4; PF07_0072). Sci Exch 5:605–605. https://doi.org/10.1038/scibx.2012.605
doi: 10.1038/scibx.2012.605
Trager W and Jensen JB (1976) Human malaria parasites in continuous culture. Science (80- ). https://doi.org/10.1126/science.781840 .
Triches F, Triches F, Lino de Oliveira C (2022) Consensus combining outcomes of multiple ensemble dockings: examples using dDAT crystalized complexes. MethodsX. https://doi.org/10.1016/j.mex.2022.101788
doi: 10.1016/j.mex.2022.101788
pubmed: 35935527
pmcid: 9352961
Tripathi M, Taylor D, Khan S, Tekwani B, Ponnan P, Subhash D, Velpandian T, Rawat D (2019) Hybridization of fluoro-amodiaquine (FAQ) with pyrimidines: synthesis and antimalarial efficacy of FAQ–Pyrimidines. ACS Med Chem Lett 10:714–719. https://doi.org/10.1021/acsmedchemlett.8b00496
doi: 10.1021/acsmedchemlett.8b00496
pubmed: 31097988
pmcid: 6511959
Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD (2002) Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45:2615–2623. https://doi.org/10.1021/jm020017n
doi: 10.1021/jm020017n
pubmed: 12036371
Vieira TF, Sousa SF (2019) Comparing AutoDock and Vina in ligand/decoy discrimination for virtual screening. Appl Sci. https://doi.org/10.3390/app9214538
doi: 10.3390/app9214538
Volkamer A, Kuhn D, Rippmann F, Rarey M (2012) Dogsitescorer: a web server for automatic binding site prediction, analysis and druggability assessment. Bioinformatics 28:2074–2075. https://doi.org/10.1093/bioinformatics/bts310
doi: 10.1093/bioinformatics/bts310
pubmed: 22628523
Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127–134. https://doi.org/10.1093/protein/8.2.127
doi: 10.1093/protein/8.2.127
pubmed: 7630882
World Health Organization (2022) World Malaria Report. World Health. ISBN 978 92 4 1564403
Xue J, Diao J, Cai G, Deng L, Zheng B, Yao Y, Song Y (2013) Antimalarial and structural studies of pyridine-containing inhibitors of 1-deoxyxylulose-5-phosphate reductoisomerase. ACS Med Chem Lett 4:278–282. https://doi.org/10.1021/ml300419r
doi: 10.1021/ml300419r
pubmed: 23795240
Zininga T, Shonhai A (2019) Small molecule inhibitors targeting the heat shock protein system of human obligate protozoan parasites. Int J Mol Sci 20:1–29. https://doi.org/10.3390/ijms20235930
doi: 10.3390/ijms20235930