Dihydrofolate Reductase (DHFR) Inhibitors: A Comprehensive Review


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Background:Dihydrofolate reductase (DHFR) is an indispensable enzyme required for the survival of most prokaryotic and eukaryotic cells as it is involved in the biosynthesis of essential cellular components. DHFR has attracted a lot of attention as a molecular target for various diseases like cancer, bacterial infection, malaria, tuberculosis, dental caries, trypanosomiasis, leishmaniasis, fungal infection, influenza, Buruli ulcer, and respiratory illness. Various teams of researchers have reported different DHFR inhibitors to explore their therapeutic efficacy. Despite all the progress made, there is a strong need to find more novel leading structures, which may be used as better and safe DHFR inhibitors, especially against the microorganisms which are resistant to the developed drug candidates.

Objective:This review aims to pay attention to recent development, particularly made in the past two decades and published in this field, and pay particular attention to promising DHFR inhibitors. Hence, an attempt has been made in this article to highlight the structure of dihydrofolate reductase, the mechanism of action of DHFR inhibitors, most recently reported DHFR inhibitors, diverse pharmacological applications of DHFR inhibitors, reported in-silico study data and recent patents based on DHFR inhibitors to comprehensively portray the current scenery for researchers interested in designing novel DHFR inhibitors.

Conclusion:A critical review of recent studies revealed that most novel DHFR inhibitor compounds either synthetically or naturally derived are characterized by the presence of heterocyclic moieties in their structure. Non-classical antifolates like trimethoprim, pyrimethamine, and proguanil are considered excellent templates to design novel DHFR inhibitors, and most of them have substituted 2,4-diamino pyrimidine motifs. Targeting DHFR has massive potential to be investigated for newer therapeutic possibilities to treat various diseases of clinical importance.

Об авторах

Renu Sehrawat

School of Medical & Allied Sciences, K R Mangalam University

Email: info@benthamscience.net

Priyanka Rathee

, SBMN Institute of Pharmaceutical Sciences and Research, B.M.U.

Email: info@benthamscience.net

Sarita Khatkar

, Vaish Institute of Pharmaceutical Education and Research

Email: info@benthamscience.net

EsraKüpeli Akkol

Department of Pharmacognosy, Faculty of Pharmacy, Gazi University

Email: info@benthamscience.net

Maryam Khayatkashani

Nutringredients Research Center, Federal Institute of Education

Email: info@benthamscience.net

Seyed Nabavi

Advanced Medical Pharma (AMP-Biotec), Biopharmaceutical Innovation Centre

Email: info@benthamscience.net

Anurag Khatkar

Department of Pharmaceutical Sciences, Maharshi Dayanand University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Hawser, S.; Lociuro, S.; Islam, K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol., 2006, 71(7), 941-948. doi: 10.1016/j.bcp.2005.10.052 PMID: 16359642
  2. Hariri, S.; Rasti, B.; Shirini, F.; Ghasemi, J.B. A combined structure-based pharmacophore modeling and 3D-QSAR study on a series of N-heterocyclic scaffolds to screen novel antagonists as human DHFR inhibitors. Struct. Chem., 2021, 32(4), 1571-1588. doi: 10.1007/s11224-020-01705-7
  3. Rao, A.S.; Tapale, S.R. A study on dihdrofolate reductase and its inhibitors: A review. Int. J. Pharm. Sci. Res., 2013, 4(2535), 2535-2547.
  4. Foye, W.O.; Lemke, T.L.; Williams, D.A. Principles of medicinal chemistry.Wolter Kluwer Health Adis, 1995.
  5. He, J.; Qiao, W.; An, Q.; Yang, T.; Luo, Y. Dihydrofolate reductase inhibitors for use as antimicrobial agents. Eur. J. Med. Chem., 2020, 195, 112268. doi: 10.1016/j.ejmech.2020.112268 PMID: 32298876
  6. Gibson, M.W.; Dewar, S.; Ong, H.B.; Sienkiewicz, N.; Fairlamb, A.H. Trypanosoma brucei DHFR-TS revisited: Characterisation of a bifunctional and highly unstable recombinant dihydrofolate reductase-thymidylate synthase. PLoS Negl. Trop. Dis., 2016, 10(5), e0004714. doi: 10.1371/journal.pntd.0004714 PMID: 27175479
  7. El-Gazzar, Y.I.; Georgey, H.H.; El-Messery, S.M.; Ewida, H.A.; Hassan, G.S.; Raafat, M.M.; Ewida, M.A.; El-Subbagh, H.I. Synthesis, biological evaluation and molecular modeling study of new (1,2,4-triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3 H )-one as DHFR inhibitors. Bioorg. Chem., 2017, 72, 282-292. doi: 10.1016/j.bioorg.2017.04.019 PMID: 28499189
  8. Fesatidou, M.; Zagaliotis, P.; Camoutsis, C.; Petrou, A.; Eleftheriou, P.; Tratrat, C.; Haroun, M.; Geronikaki, A.; Ciric, A.; Sokovic, M. 5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design, synthesis, molecular docking and evaluation. Bioorg. Med. Chem., 2018, 26(16), 4664-4676. doi: 10.1016/j.bmc.2018.08.004 PMID: 30107969
  9. Polshakov, V.I. Dihydrofolate reductase: Structural aspects of mechanisms of enzyme catalysis and inhibition. Russ. Chem. Bull., 2001, 50(10), 1733-1751. doi: 10.1023/A:1014313625350
  10. Kitchen, D.B.; Decornez, H.; Furr, J.R.; Bajorath, J. Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat. Rev. Drug Discov., 2004, 3(11), 935-949. doi: 10.1038/nrd1549 PMID: 15520816
  11. Then, R.L. Antimicrobial dihydrofolate reductase inhibitors achievements and future options: Review. J. Chemother., 2004, 16(1), 3-12. doi: 10.1179/joc.2004.16.1.3 PMID: 15077993
  12. Huang, D.B.; Strader, C.D.; MacDonald, J.S.; VanArendonk, M.; Peck, R.; Holland, T. An updated review of iclaprim: A potent and rapidly bactericidal antibiotic for the treatment of skin and skin structure infections and nosocomial pneumonia caused by gram-positive including multidrug-resistant bacteria. Open Forum Infect. Dis., 2018, 5(2), ofy003. doi: 10.1093/ofid/ofy003 PMID: 29423421
  13. Krajinovic, M.; Abaji, R.; Sharif-Askari, B. DHFR (dihydrofolate reductase). Atlas Genet. Cytogenet. Oncol. Haematol., 2018. doi: 10.4267/2042/66069
  14. da Cunha, E.F.F.; Ramalho, T.C.; Maia, E.R.; de Alencastro, R.B. The search for new DHFR inhibitors: A review of patents, January 2001 – February 2005. Expert Opin. Ther. Pat., 2005, 15(8), 967-986. doi: 10.1517/13543776.15.8.967
  15. Raimondi, M.; Randazzo, O.; La Franca, M.; Barone, G.; Vignoni, E.; Rossi, D.; Collina, S. DHFR inhibitors: Reading the past for discovering novel anticancer agents. Molecules, 2019, 24(6), 1140. doi: 10.3390/molecules24061140 PMID: 30909399
  16. Wang, M.; Yang, J.; Yuan, M.; Xue, L.; Li, H.; Tian, C.; Wang, X.; Liu, J.; Zhang, Z. Synthesis and antiproliferative activity of a series of novel 6-substituted pyrido3,2- d pyrimidines as potential nonclassical lipophilic antifolates targeting dihydrofolate reductase. Eur. J. Med. Chem., 2017, 128, 88-97. doi: 10.1016/j.ejmech.2017.01.033 PMID: 28152430
  17. Ducker, G.S.; Rabinowitz, J.D. One-carbon metabolism in health and disease. Cell Metab., 2017, 25(1), 27-42. doi: 10.1016/j.cmet.2016.08.009 PMID: 27641100
  18. Brown, P.M.; Pratt, A.G.; Isaacs, J.D. Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nat. Rev. Rheumatol., 2016, 12(12), 731-742. doi: 10.1038/nrrheum.2016.175 PMID: 27784891
  19. Nordberg, M.G. Approaches to Soft Drug Analogues of Dihydrofolate Reductase Inhibitors, PhD thesis, Acta Universitatis Upsaliensis. 2001.
  20. Cao, H.; Gao, M.; Zhou, H.; Skolnick, J. The crystal structure of a tetrahydrofolate-bound dihydrofolate reductase reveals the origin of slow product release. Commun. Biol., 2018, 1(1), 226. doi: 10.1038/s42003-018-0236-y PMID: 30564747
  21. Macreadie, I.; Ginsburg, H.; Sirawaraporn, W.; Tilley, L. Antimalarial drug development and new targets. Parasitol. Today, 2000, 16(10), 438-444. doi: 10.1016/S0169-4758(00)01758-0 PMID: 11006476
  22. Wróbel, A.; Drozdowska, D. Recent design and structure-activity relationship studies on the modifications of DHFR inhibitors as anticancer agents. Curr. Med. Chem., 2021, 28(5), 910-939. doi: 10.2174/1875533XMTAxnNTQey PMID: 31622199
  23. Cody, V.; Schwalbe, C.H. Structural characteristics of antifolate dihydrofolate reductase enzyme interactions. Crystallogr. Rev., 2006, 12(4), 301-333. doi: 10.1080/08893110701337727
  24. Mhashal, A.R.; Vardi-Kilshtain, A.; Kohen, A.; Major, D.T. The role of the Met20 loop in the hydride transfer in Escherichia coli dihydrofolate reductase. J. Biol. Chem., 2017, 292(34), 14229-14239. doi: 10.1074/jbc.M117.777136 PMID: 28620051
  25. Oliveira, A.A.; Rennó, M.N.; de Matos, C.A.S.; Bertuzzi, M.D.; Ramalho, T.C.; Fraga, C.A.M.; França, T.C.C. Molecular modeling studies of Yersinia pestis dihydrofolate reductase. J. Biomol. Struct. Dyn., 2011, 29(2), 351-367. doi: 10.1080/07391102.2011.10507390 PMID: 21875154
  26. Zuccotto, F.; Martin, A.C.R.; Laskowski, R.A.; Thornton, J.M.; Gilbert, I.H. Dihydrofolate reductase: A potential drug target in trypanosomes and leishmania. J. Comput. Aided Mol. Des., 1998, 12(3), 241-257. doi: 10.1023/A:1016085005275 PMID: 9749368
  27. Cummins, J. Antimicrobial resistance. N. Z. Med. J., 1999, 112(1087), 166-167. PMID: 10378813
  28. Moran, G.J.; Krishnadasan, A.; Gorwitz, R.J.; Fosheim, G.E.; McDougal, L.K.; Carey, R.B.; Talan, D.A. Methicillin-resistant S. aureus infections among patients in the emergency department. N. Engl. J. Med., 2006, 355(7), 666-674. doi: 10.1056/NEJMoa055356 PMID: 16914702
  29. Fridkin, S.K.; Hageman, J.C.; Morrison, M.; Sanza, L.T.; Como-Sabetti, K.; Jernigan, J.A.; Harriman, K.; Harrison, L.H.; Lynfield, R.; Farley, M.M. Methicillin-resistant staphylococcus aureus disease in three communities. Active bacterial core surveillance program of the emerging infections program network N. Engl. J. Med., 2005, 352(14), 1436-1444. doi: 10.1056/NEJMoa043252 PMID: 15814879
  30. Kumar, M.; Dagar, A.; Gupta, V.K.; Sharma, A. In silico docking studies of bioactive natural plant products as putative DHFR antagonists. Med. Chem. Res., 2014, 23(2), 810-817. doi: 10.1007/s00044-013-0654-9 PMID: 25620864
  31. Mokmak, W.; Chunsrivirot, S.; Hannongbua, S.; Yuthavong, Y.; Tongsima, S.; Kamchonwongpaisan, S. Molecular dynamics of interactions between rigid and flexible antifolates and dihydrofolate reductase from pyrimethamine-sensitive and pyrimethamine-resistant Plasmodium falciparum. Chem. Biol. Drug Des., 2014, 84(4), 450-461. doi: 10.1111/cbdd.12334 PMID: 24716467
  32. Gregson, A.; Plowe, C.V. Mechanisms of resistance of malaria parasites to antifolates. Pharmacol. Rev., 2005, 57(1), 117-145. doi: 10.1124/pr.57.1.4 PMID: 15734729
  33. Bolstad, D.B.; Bolstad, E.S.D.; Wright, D.L.; Anderson, A.C. Dihydrofolate reductase inhibitors: Developments in antiparasitic chemotherapy. Expert Opin. Ther. Pat., 2008, 18(2), 143-157. doi: 10.1517/13543776.18.2.143 PMID: 20553119
  34. Alam, M.S.; Saleh, M.A.; Mozibullah, M.; Riham, A.T.; Solayman, M.; Gan, S.H. Computational algorithmic and molecular dynamics study of functional and structural impacts of non-synonymous single nucleotide polymorphisms in human DHFR gene. Comput. Biol. Chem., 2021, 95, 107587. doi: 10.1016/j.compbiolchem.2021.107587 PMID: 34710812
  35. Matthews, D.A.; Bolin, J.T.; Burridge, J.M.; Filman, D.J.; Volz, K.W.; Kaufman, B.T.; Beddell, C.R.; Champness, J.N.; Stammers, D.K.; Kraut, J. Refined crystal structures of Escherichia coli and chicken liver dihydrofolate reductase containing bound trimethoprim. J. Biol. Chem., 1985, 260(1), 381-391. doi: 10.1016/S0021-9258(18)89743-5 PMID: 3880742
  36. Wróbel, A.; Arciszewska, K.; Maliszewski, D.; Drozdowska, D. Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors. J. Antibiot., 2020, 73(1), 5-27. doi: 10.1038/s41429-019-0240-6 PMID: 31578455
  37. Eliopoulos, G.M.; Huovinen, P. Resistance to trimethoprim-sulfamethoxazole. Clin. Infect. Dis., 2001, 32(11), 1608-1614. doi: 10.1086/320532 PMID: 11340533
  38. Libecco, J.A.; Powell, K.R.; Miller, N. Trimethoprim/Sulfamethoxazole. Pediatr. Rev., 2004, 25(11), 375-380. doi: 10.1542/pir.25.11.375 PMID: 15520082
  39. Farber, S.; Diamond, L.K.; Mercer, R.D.; Sylvester, R.F., Jr; Wolff, J.A. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N. Engl. J. Med., 1948, 238(23), 787-793. doi: 10.1056/NEJM194806032382301 PMID: 18860765
  40. Blaney, J.M.; Hansch, C.; Silipo, C.; Vittoria, A. Structure-activity relationships of dihydrofolated reductase inhibitors. Chem. Rev., 1984, 84(4), 333-407. doi: 10.1021/cr00062a002
  41. Srinivasan, B.; Skolnick, J. Insights into the slow-onset tight-binding inhibition of Escherichia coli dihydrofolate reductase: detailed mechanistic characterization of pyrrolo 3,2- f quinazoline-1,3-diamine and its derivatives as novel tight-binding inhibitors. FEBS J., 2015, 282(10), 1922-1938. doi: 10.1111/febs.13244 PMID: 25703118
  42. Zhang, Y.; Chowdhury, S.; Rodrigues, J.V.; Shakhnovich, E. Development of antibacterial compounds that constrain evolutionary pathways to resistance. eLife, 2021, 10, e64518. doi: 10.7554/eLife.64518 PMID: 34279221
  43. Gangjee, A.; Jain, H.D.; Phan, J.; Lin, X.; Song, X.; McGuire, J.J.; Kisliuk, R.L. Dual inhibitors of thymidylate synthase and dihydrofolate reductase as antitumor agents: design, synthesis, and biological evaluation of classical and nonclassical pyrrolo2,3-dpyrimidine antifolates(1). J. Med. Chem., 2006, 49(3), 1055-1065. doi: 10.1021/jm058276a PMID: 16451071
  44. Shinde, G.H.; Pekamwar, S.S. An overview on dihydrofolate reductase inhibitors. Int. J. Chem. Pham. Sci., 2013, 4, 8-17.
  45. Singh, A.; Deshpande, N.; Pramanik, N.; Jhunjhunwala, S.; Rangarajan, A.; Atreya, H.S. Optimized peptide based inhibitors targeting the dihydrofolate reductase pathway in cancer. Sci. Rep., 2018, 8(1), 3190. doi: 10.1038/s41598-018-21435-5 PMID: 29453377
  46. Tonelli, M.; Naesens, L.; Gazzarrini, S.; Santucci, M.; Cichero, E.; Tasso, B.; Moroni, A.; Costi, M.P.; Loddo, R. Host dihydrofolate reductase (DHFR)-directed cycloguanil analogues endowed with activity against influenza virus and respiratory syncytial virus. Eur. J. Med. Chem., 2017, 135, 467-478. doi: 10.1016/j.ejmech.2017.04.070 PMID: 28477572
  47. Liu, J.; Bolstad, D.B.; Bolstad, E.S.D.; Wright, D.L.; Anderson, A.C. Towards new antifolates targeting eukaryotic opportunistic infections. Eukaryot. Cell, 2009, 8(4), 483-486. doi: 10.1128/EC.00298-08 PMID: 19168759
  48. Anderson, A.C.; Wright, D.L. Antifolate agents: A patent review (2010 – 2013). Expert Opin. Ther. Pat., 2014, 24(6), 687-697. doi: 10.1517/13543776.2014.898062 PMID: 24655343
  49. Wang, Y.; Lu, H.; Sun, L.; Chen, X.; Wei, H.; Suo, C.; Feng, J.; Yuan, M.; Shen, S.; Jia, W.; Wang, Y.; Zhang, H.; Li, Z.; Zhong, X.; Gao, P. Metformin sensitises hepatocarcinoma cells to methotrexate by targeting dihydrofolate reductase. Cell Death Dis., 2021, 12(10), 902. doi: 10.1038/s41419-021-04199-1 PMID: 34601503
  50. Zhou, X.; Lin, K.; Ma, X.; Chui, W.K.; Zhou, W. Design, synthesis, docking studies and biological evaluation of novel dihydro-1,3,5-triazines as human DHFR inhibitors. Eur. J. Med. Chem., 2017, 125, 1279-1288. doi: 10.1016/j.ejmech.2016.11.010 PMID: 27886545
  51. Riyadh, S.M.; El-Motairi, S.A.; Ahmed, H.E.A.; Khalil, K.D.; Habib, E.L.S.E. Synthesis, biological evaluation, and molecular docking of novel thiazoles and 1,3,4thiadiazoles incorporating sulfonamide group as DHFR inhibitors. Chem. Biodivers., 2018, 15(9), e1800231. doi: 10.1002/cbdv.201800231 PMID: 29956887
  52. Fargualy, A.M.; Habib, N.S.; Ismail, K.A.; Hassan, A.M.M.; Sarg, M.T.M. Synthesis, biological evaluation and molecular docking studies of some pyrimidine derivatives. Eur. J. Med. Chem., 2013, 66, 276-295. doi: 10.1016/j.ejmech.2013.05.028 PMID: 23811090
  53. Ewida, M.A.; Abou El Ella, D.A.; Lasheen, D.S.; Ewida, H.A.; El-Gazzar, Y.I.; El-Subbagh, H.I. Imidazo2′,1′:2,3thiazolo4,5-dpyridazinone as a new scaffold of DHFR inhibitors: Synthesis, biological evaluation and molecular modeling study. Bioorg. Chem., 2018, 80, 11-23. doi: 10.1016/j.bioorg.2018.05.025 PMID: 29864684
  54. Ewida, M.A.; Abou El Ella, D.A.; Lasheen, D.S.; Ewida, H.A.; El-Gazzar, Y.I.; El-Subbagh, H.I. Thiazolo4,5- d pyridazine analogues as a new class of dihydrofolate reductase (DHFR) inhibitors: Synthesis, biological evaluation and molecular modeling study. Bioorg. Chem., 2017, 74, 228-237. doi: 10.1016/j.bioorg.2017.08.010 PMID: 28865294
  55. Algul, O.; Paulsen, J.L.; Anderson, A.C. 2,4-Diamino-5-(2′-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition. J. Mol. Graph. Model., 2011, 29(5), 608-613. doi: 10.1016/j.jmgm.2010.11.004 PMID: 21146434
  56. Hobani, Y.; Jerah, A.; Bidwai, A. A comparative molecular docking study of curcumin and methotrexate to dihydrofolate reductase. Bioinformation, 2017, 13(3), 63-66. doi: 10.6026/97320630013063 PMID: 28584445
  57. Aslan, E.; Adem, S. Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity. J. Biochem. Mol. Toxicol., 2015, 29(3), 135-139. doi: 10.1002/jbt.21677 PMID: 25418905
  58. Sánchez-del-Campo, L.; Sáez-Ayala, M.; Chazarra, S.; Cabezas-Herrera, J.; Rodríguez-López, J.N. Binding of natural and synthetic polyphenols to human dihydrofolate reductase. Int. J. Mol. Sci., 2009, 10(12), 5398-5410. doi: 10.3390/ijms10125398 PMID: 20054477
  59. El-Subbagh, H.I.; Hassan, G.S.; El-Messery, S.M.; Al-Rashood, S.T.; Al-Omary, F.A.M.; Abulfadl, Y.S.; Shabayek, M.I. Nonclassical antifolates, part 5. Benzodiazepine analogs as a new class of DHFR inhibitors: Synthesis, antitumor testing and molecular modeling study. Eur. J. Med. Chem., 2014, 74, 234-245. doi: 10.1016/j.ejmech.2014.01.004 PMID: 24469112
  60. El-Shershaby, M.H.; El-Gamal, K.M.; Bayoumi, A.H.; El-Adl, K.; Alswah, M.; Ahmed, H.E.A.; Al-Karmalamy, A.A.; Abulkhair, H.S. The antimicrobial potential and pharmacokinetic profiles of novel quinoline-based scaffolds: Synthesis and in silico mechanistic studies as dual DNA gyrase and DHFR inhibitors. New J. Chem., 2021, 45(31), 13986-14004. doi: 10.1039/D1NJ02838C
  61. Ragab, A.; Fouad, S.A.; Ali, O.A.A.; Ahmed, E.M.; Ali, A.M.; Askar, A.A.; Ammar, Y.A. Sulfaguanidine hybrid with some new pyridine-2-one derivatives: Design, synthesis, and antimicrobial activity against multidrug-resistant bacteria as dual DNA gyrase and DHFR inhibitors. Antibiotics, 2021, 10(2), 162. doi: 10.3390/antibiotics10020162 PMID: 33562582
  62. Li, Y.; Ouyang, Y.; Wu, H.; Wang, P.; Huang, Y.; Li, X.; Chen, H.; Sun, Y.; Hu, X.; Wang, X.; Li, G.; Lu, Y.; Li, C.; Lu, X.; Pang, J.; Nie, T.; Sang, X.; Dong, L.; Dong, W.; Jiang, J.; Paterson, I.C.; Yang, X.; Hong, W.; Wang, H.; You, X. The discovery of 1, 3-diamino-7H-pyrrol3, 2-fquinazoline compounds as potent antimicrobial antifolates. Eur. J. Med. Chem., 2021, 113979 doi: 10.1016/j.ejmech.2021.113979 PMID: 34802838
  63. Rashid, U.; Ahmad, W.; Hassan, S.F.; Qureshi, N.A.; Niaz, B.; Muhammad, B.; Imdad, S.; Sajid, M. Design, synthesis, antibacterial activity and docking study of some new trimethoprim derivatives. Bioorg. Med. Chem. Lett., 2016, 26(23), 5749-5753. doi: 10.1016/j.bmcl.2016.10.051 PMID: 28327306
  64. Dinari, M.; Gharahi, F.; Asadi, P. Synthesis, spectroscopic characterization, antimicrobial evaluation and molecular docking study of novel triazine-quinazolinone based hybrids. J. Mol. Struct., 2018, 1156, 43-50. doi: 10.1016/j.molstruc.2017.11.087
  65. Debbabi, K.F.; Bashandy, M.S.; Al-Harbi, S.A.; Aljuhani, E.H.; Al-Saidi, H.M. Synthesis and molecular docking against dihydrofolate reductase of novel pyridin-N-ethyl-N-methylbenzenesulfonamides as efficient anticancer and antimicrobial agents. J. Mol. Struct., 2017, 1131, 124-135. doi: 10.1016/j.molstruc.2016.11.048
  66. Gschwend, D.A.; Sirawaraporn, W.; Santi, D.V.; Kuntz, I.D. Specificity in structure-based drug design: Identification of a novel, selective inhibitor ofPneumocystis carinii dihydrofolate reductase. Proteins, 1997, 29(1), 59-67. doi: 10.1002/(SICI)1097-0134(199709)29:13.0.CO;2-A PMID: 9294866
  67. Jackson, H.C.; Biggadike, K.; McKilligin, E.; Kinsman, O.S.; Queener, S.F.; Lane, A.; Smith, J.E. 6,7-disubstituted 2,4-diaminopteridines: Novel inhibitors of Pneumocystis carinii and toxoplasma gondii dihydrofolate reductase. Antimicrob. Agents Chemother., 1996, 40(6), 1371-1375. doi: 10.1128/AAC.40.6.1371 PMID: 8726003
  68. Liu, J.; Bolstad, D.B.; Smith, A.E.; Priestley, N.D.; Wright, D.L.; Anderson, A.C. The crystal structure of Candida glabrata dihydrofolate reductase drives new inhibitor design toward efficacious antifungal agents. Chem. Biol., 2008, 15(9), 990. doi: 10.1016/j.chembiol.2008.07.013 PMID: 18804036
  69. Dewangan, D.; Vaishnav, Y.; Mishra, A.; Jha, A.K.; Verma, S.; Badwaik, H. Synthesis, molecular docking, and biological evaluation of Schiff base hybrids of 1,2,4-triazole-pyridine as dihydrofolate reductase inhibitors. Curr Res Pharmacol Drug Discov, 2021, 2, 100024. doi: 10.1016/j.crphar.2021.100024 PMID: 34909659
  70. Buruli ulcer. Available From: https://www.who.int/news-room/fact-sheets/detail/buruli-ulcer-(Accessed on: December 1, 2021).
  71. Riboldi, G.P.; Zigweid, R.; Myler, P.J.; Mayclin, S.J.; Couñago, R.M.; Staker, B.L. Identification of P218 as a potent inhibitor of Mycobacterium ulcerans DHFR. RSC Medicinal Chemistry, 2021, 12(1), 103-109. doi: 10.1039/D0MD00303D PMID: 34046602
  72. Desai, N.C.; Trivedi, A.R.; Khedkar, V.M. Preparation, biological evaluation and molecular docking study of imidazolyl dihydropyrimidines as potential Mycobacterium tuberculosis dihydrofolate reductase inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(16), 4030-4035. doi: 10.1016/j.bmcl.2016.06.082 PMID: 27397497
  73. Sharma, K.; Tanwar, O.; Sharma, S.; Ali, S.; Alam, M.M.; Zaman, M.S.; Akhter, M. Structural comparison of Mtb-DHFR and h-DHFR for design, synthesis and evaluation of selective non-pteridine analogues as antitubercular agents. Bioorg. Chem., 2018, 80, 319-333. doi: 10.1016/j.bioorg.2018.04.022 PMID: 29986181
  74. Aragaw, W.W.; Lee, B.M.; Yang, X.; Zimmerman, M.D.; Gengenbacher, M.; Dartois, V.; Chui, W.K.; Jackson, C.J.; Dick, T. Potency boost of a Mycobacterium tuberculosis dihydrofolate reductase inhibitor by multienzyme F 420 H 2 -dependent reduction. Proc. Natl. Acad. Sci. USA, 2021, 118(25), e2025172118. doi: 10.1073/pnas.2025172118 PMID: 34161270
  75. Malaria. Available From: https://www.who.int/news-room/fact-sheets/detail/malaria (Accessed on: December 1, 2021).
  76. Ivanetich, K.M.; Santi, D.V. Thymidylate synthase-dihydrofolate reductase in protozoa. Exp. Parasitol., 1990, 70(3), 367-371. doi: 10.1016/0014-4894(90)90119-W PMID: 2178951
  77. Thakkar, S.S.; Thakor, P.; Doshi, H.; Ray, A. 1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities. Bioorg. Med. Chem., 2017, 25(15), 4064-4075. doi: 10.1016/j.bmc.2017.05.054 PMID: 28634040
  78. Thakkar, S.S.; Thakor, P.; Ray, A.; Doshi, H.; Thakkar, V.R. Benzothiazole analogues: Synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities. Bioorg. Med. Chem., 2017, 25(20), 5396-5406. doi: 10.1016/j.bmc.2017.07.057 PMID: 28789907
  79. Bekhit, A.A.; Saudi, M.N.; Hassan, A.M.M.; Fahmy, S.M.; Ibrahim, T.M.; Ghareeb, D.; El-Seidy, A.M.; Nasralla, S.N.; Bekhit, A.E.D.A. Synthesis, in silico experiments and biological evaluation of 1,3,4-trisubstituted pyrazole derivatives as antimalarial agents. Eur. J. Med. Chem., 2019, 163, 353-366. doi: 10.1016/j.ejmech.2018.11.067 PMID: 30530172
  80. Gahtori, P.; Ghosh, S.K.; Parida, P.; Prakash, A.; Gogoi, K.; Bhat, H.R.; Singh, U.P. Antimalarial evaluation and docking studies of hybrid phenylthiazolyl-1,3,5-triazine derivatives: A novel and potential antifolate lead for Pf-DHFR-TS inhibition. Exp. Parasitol., 2012, 130(3), 292-299. doi: 10.1016/j.exppara.2011.12.014 PMID: 22233734
  81. Patel, T.S.; Vanparia, S.F.; Patel, U.H.; Dixit, R.B.; Chudasama, C.J.; Patel, B.D.; Dixit, B.C. Novel 2,3-disubstituted quinazoline-4(3H)-one molecules derived from amino acid linked sulphonamide as a potent malarial antifolates for DHFR inhibition. Eur. J. Med. Chem., 2017, 129, 251-265. doi: 10.1016/j.ejmech.2017.02.012 PMID: 28231522
  82. Hopper, A.T.; Brockman, A.; Wise, A.; Gould, J.; Barks, J.; Radke, J.B.; Sibley, L.D.; Zou, Y.; Thomas, S. Discovery of selective Toxoplasma gondii dihydrofolate reductase inhibitors for the treatment of toxoplasmosis. J. Med. Chem., 2019, 62(3), 1562-1576. doi: 10.1021/acs.jmedchem.8b01754 PMID: 30624926
  83. Singh, I.V.; Mishra, S. Molecular docking analysis of pyrimethamine derivatives with plasmodium falciparum dihydrofolate reductase. Bioinformation, 2018, 14(5), 232-235. doi: 10.6026/97320630014232 PMID: 30108420
  84. Francesconi, V.; Giovannini, L.; Santucci, M.; Cichero, E.; Costi, M.P.; Naesens, L.; Giordanetto, F.; Tonelli, M. Synthesis, biological evaluation and molecular modeling of novel azaspiro dihydrotriazines as influenza virus inhibitors targeting the host factor dihydrofolate reductase (DHFR). Eur. J. Med. Chem., 2018, 155, 229-243. doi: 10.1016/j.ejmech.2018.05.059 PMID: 29886325
  85. Zhang, Q.; Nguyen, T.; McMichael, M.; Velu, S.E.; Zou, J.; Zhou, X.; Wu, H. New small-molecule inhibitors of dihydrofolate reductase inhibit Streptococcus mutans. Int. J. Antimicrob. Agents, 2015, 46(2), 174-182. doi: 10.1016/j.ijantimicag.2015.03.015 PMID: 26022931
  86. Kelotra, A.; Soumya, V.; Kelotra, S.; Gokhale, S.M.; Bidwai, A. Molecular docking of some herbal-based potential anti-psoriasis agents with dihydrofolate reductase. Ind. J. Drug Dis., 2012, 1(8)
  87. World Health Organization (WHO). Leishmaniasis. Available From: https://www.who.int/news-room/fact-sheets/detail/leishmaniasis (Accessed on: December 1, 2021).
  88. Cavazzuti, A.; Paglietti, G.; Hunter, W.N.; Gamarro, F.; Piras, S.; Loriga, M.; Allecca, S.; Corona, P.; McLuskey, K.; Tulloch, L.; Gibellini, F.; Ferrari, S.; Costi, M.P. Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development. Proc. Natl. Acad. Sci., 2008, 105(5), 1448-1453. doi: 10.1073/pnas.0704384105 PMID: 18245389
  89. Bibi, M.; Qureshi, N.A.; Sadiq, A.; Farooq, U.; Hassan, A.; Shaheen, N.; Asghar, I.; Umer, D.; Ullah, A.; Khan, F.A.; Salman, M.; Bibi, A.; Rashid, U. Exploring the ability of dihydropyrimidine-5-carboxamide and 5-benzyl-2,4-diaminopyrimidine-based analogues for the selective inhibition of L. major dihydrofolate reductase. Eur. J. Med. Chem., 2021, 210, 112986. doi: 10.1016/j.ejmech.2020.112986 PMID: 33187806
  90. Schüttelkopf, A.W.; Hardy, L.W.; Beverley, S.M.; Hunter, W.N. Structures of Leishmania major pteridine reductase complexes reveal the active site features important for ligand binding and to guide inhibitor design. J. Mol. Biol., 2005, 352(1), 105-116. doi: 10.1016/j.jmb.2005.06.076 PMID: 16055151
  91. Maganti, L.; Manoharan, P.; Ghoshal, N. Probing the structure of Leishmania donovani chagasi DHFR-TS: comparative protein modeling and protein–ligand interaction studies. J. Mol. Model., 2010, 16(9), 1539-1547. doi: 10.1007/s00894-010-0649-0 PMID: 20174846
  92. Available From: https://go.drugbank.com/ drugs/ DB03695 (Accessed on: December 1, 2021)
  93. Lémann, M.; Zenjari, T.; Bouhnik, Y.; Cosnes, J.; Mesnard, B.; Rambaud, J.C.; Modigliani, R.; Cortot, A.; Colombel, J.F. Methotrexate in Crohn’s disease: Long-term efficacy and toxicity. Am. J. Gastroenterol., 2000, 95(7), 1730-1734. doi: 10.1111/j.1572-0241.2000.02190.x PMID: 10925976
  94. Vidmar, M.; Grželj, J.; Mlinarič-Raščan, I.; Geršak, K.; Dolenc, M.S. Medicines associated with folate–homocysteine–methionine pathway disruption. Arch. Toxicol., 2019, 93(2), 227-251. doi: 10.1007/s00204-018-2364-z PMID: 30499019
  95. Petersen, E. The safety of atovaquone/proguanil in long-term malaria prophylaxis of nonimmune adults. J. Travel Med., 2003, 10, S13-S15. doi: 10.2310/7060.2003.35050 PMID: 12737755
  96. Available From: https://www.drugs.com/search.php? searchterm=pemetrexed&a=1 (Accessed on: July 27, 2021).
  97. FDA Approves Folotyn (pralatrexate) for Treatment of Peripheral T-cell Lymphoma. Available From: https://www.drugs.com/newdrugs/fda-approves-folotyn-pralatrexate-peripheral-t-cell-lymphoma-1666.html (Accessed on: December 1, 2021).
  98. Andersen, J.T.; Petersen, M.; Jimenez-Solem, E.; Broedbaek, K.; Andersen, E.W.; Andersen, N.L.; Afzal, S.; Torp-Pedersen, C.; Keiding, N.; Poulsen, H.E. Trimethoprim use in early pregnancy and the risk of miscarriage: A register-based nationwide cohort study. Epidemiol. Infect., 2013, 141(8), 1749-1755. doi: 10.1017/S0950268812002178 PMID: 23010291
  99. Salako, L.A. Toxicity and side-effects of antimalarials in Africa: A critical review. Bull. World Health Organ., 1984.
  100. Proguanil. Available From: https://go.drugbank.com/drugs/DB01131 (Accessed on: December 1, 2021).
  101. Andrejko, K.L.; Mayer, R.C.; Kovacs, S.; Slutsker, E.; Bartlett, E.; Tan, K.R.; Gutman, J.R. The safety of atovaquone-proguanil for the prevention and treatment of malaria in pregnancy: A systematic review. Travel Med. Infect. Dis., 2019, 27, 20-26. doi: 10.1016/j.tmaid.2019.01.008 PMID: 30654041
  102. Patents. Fuel Cells Bull., 2019, 2019(4), 16-19. doi: 10.1016/S1464-2859(19)30172-5
  103. Espacenet. Patent search. 2021. Available From: https://worldwide.espacenet.com/searchResults?search=DHFR+inhibitors&DB=EPODOC&submitted=true&locale=en_EP&ST=singleline&compact=-false&DB=EPODOC&query=DHFR+inhibitors&DB=EPODOC&submitted=true&locale=en_EP&ST=singleline&compact=false&DB=EPODOC&query=DHFR+i (Accessed on: July 5, 2021).

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