Login Register Cart 0
Review Article

二氢叶酸还原酶(DHFR)抑制剂:综合综述

卷 31, 期 7, 2024

发表于: 19 May, 2023

页: [799 - 824] 页: 26

弟呕挨: 10.2174/0929867330666230310091510

价格: $65

conference banner
摘要

背景: 二氢叶酸还原酶(DHFR)是大多数原核和真核细胞生存所必需的酶，因为它参与了细胞必需成分的生物合成。DHFR作为癌症、细菌感染、疟疾、结核病、龋齿、锥虫病、利什曼病、真菌感染、流感、布鲁里溃疡和呼吸系统疾病等多种疾病的分子靶点，引起了广泛关注。不同的研究小组已经报道了不同的DHFR抑制剂来探索它们的治疗效果。尽管取得了所有这些进展，但迫切需要找到更多新的先导结构，这些结构可能用作更好和安全的DHFR抑制剂，特别是针对对已开发的候选药物耐药的微生物。 目的：本综述旨在关注该领域的最新进展，特别是过去二十年来在该领域取得的进展和发表的文章，并特别关注有前景的DHFR抑制剂。因此，本文试图重点介绍二氢叶酸还原酶的结构、DHFR抑制剂的作用机制、最近报道的DHFR抑制剂、DHFR抑制剂的各种药理学应用、已报道的硅研究数据和基于DHFR抑制剂的最新专利，以全面描绘对设计新型DHFR抑制剂感兴趣的研究人员的现状。 结论：最近的一项研究表明，大多数新的DHFR抑制剂化合物，无论是合成的还是天然衍生的，都以其结构中存在杂环部分为特征。非经典抗叶酸药物如甲氧苄啶、乙胺嘧啶和proguanil被认为是设计新型DHFR抑制剂的优秀模板，它们大多数具有取代的2,4-二氨基嘧啶基序。靶向DHFR具有巨大的潜力被研究用于治疗各种临床重要疾病的新治疗可能性。

关键词: 二氢叶酸还原酶(DHFR)抑制剂，结核，乙胺嘧啶，酶，甲氨蝶呤，甲氧苄啶。

« Previous Next »
[1]
Hawser, S.; Lociuro, S.; Islam, K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol., 2006, 71(7), 941-948.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1093/ofid/ofy003] [PMID: 29423421]
[13]
Krajinovic, M.; Abaji, R.; Sharif-Askari, B. DHFR (dihydrofolate reductase). Atlas Genet. Cytogenet. Oncol. Haematol., 2018.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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 pyrido[3,2- d ]pyrimidines as potential nonclassical lipophilic antifolates targeting dihydrofolate reductase. Eur. J. Med. Chem., 2017, 128, 88-97.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1086/320532] [PMID: 11340533]
[38]
Libecco, J.A.; Powell, K.R.; Miller, N. Trimethoprim/Sulfamethoxazole. Pediatr. Rev., 2004, 25(11), 375-380.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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 pyrrolo[2,3-d]pyrimidine antifolates(1). J. Med. Chem., 2006, 49(3), 1055-1065.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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 [1,3,4]thiadiazoles incorporating sulfonamide group as DHFR inhibitors. Chem. Biodivers., 2018, 15(9), e1800231.
[http://dx.doi.org/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.
[http://dx.doi.org/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. Imidazo[2′,1′:2,3]thiazolo[4,5-d]pyridazinone as a new scaffold of DHFR inhibitors: Synthesis, biological evaluation and molecular modeling study. Bioorg. Chem., 2018, 80, 11-23.
[http://dx.doi.org/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. Thiazolo[4,5- 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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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-pyrrol[3, 2-f]quinazoline compounds as potent antimicrobial antifolates. Eur. J. Med. Chem., 2021, 113979
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1002/(SICI)1097-0134(199709)29:1<59::AID-PROT4>3.0.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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1016/j.tmaid.2019.01.008] [PMID: 30654041]
[102]
Patents. Fuel Cells Bull., 2019, 2019(4), 16-19.
[http://dx.doi.org/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).

Rights & Permissions Print Cite
Article Metrics
80
5
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy