Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Ninety Years of Pentamidine: The Development and Applications of Pentamidine and its Analogs

Author(s): Bo Zhang, Yushan Jin, Lei Zhang, Hongshuang Wang* and Xiaohui Wang*

Volume 29, Issue 26, 2022

Published on: 12 April, 2022

Page: [4602 - 4609] Pages: 8

DOI: 10.2174/0929867329666220314121446

Price: $65

Abstract

Pentamidine, an FDA-approved human drug for many protozoal infections, was initially synthesized in the late 1930s and first reported to be curative for parasitosis in the 1940s. After ninety years of sometimes quiet growth, pentamidine and its derivatives have gone far beyond antibacterial agents, including but not limited to the ligands of DNA minor groove, modulators of PPIs (protein-protein interactions) of the transmembrane domain 5 of lateral membrane protein 1, and the blockers of the SARS-CoV-2 3a channel. This mini-review highlights the development and applications of pentamidine and its analogs, aiming to provide insights for further developing pentamidine derivatives in the following decades.

Keywords: Pentamidine, antimicrobial drug, DNA minor groove ligands, SARS-CoV-2, 3a channel, inhibitors of PPIs, amidine.

« Previous Next »
[1]
Leoung, G.S.; Feigal, D.W., Jr; Montgomery, A.B.; Corkery, K.; Wardlaw, L.; Adams, M.; Busch, D.; Gordon, S.; Jacobson, M.A.; Volberding, P.A. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco community prophylaxis trial. N. Engl. J. Med., 1990, 323(12), 769-775.
[http://dx.doi.org/10.1056/NEJM199009203231201] [PMID: 1975426]
[2]
Nguewa, P.A.; Fuertes, M.A.; Cepeda, V.; Iborra, S.; Carrión, J.; Valladares, B.; Alonso, C.; Pérez, J.M. Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin. Chem. Biodivers., 2005, 2(10), 1387-1400.
[http://dx.doi.org/10.1002/cbdv.200590111] [PMID: 17191940]
[3]
Kovacs, J.A.; Masur, H. Evolving health effects of Pneumocystis: One hundred years of progress in diagnosis and treatment. JAMA, 2009, 301(24), 2578-2585.
[http://dx.doi.org/10.1001/jama.2009.880] [PMID: 19549975]
[4]
Nok, A.J. Arsenicals (melarsoprol), pentamidine and suramin in the treatment of human African trypanosomiasis. Parasitol. Res., 2003, 90(1), 71-79.
[http://dx.doi.org/10.1007/s00436-002-0799-9] [PMID: 12743807]
[5]
Singh, S.; Sivakumar, R. Challenges and new discoveries in the treatment of leishmaniasis. J. Infect. Chemother., 2004, 10(6), 307-315.
[http://dx.doi.org/10.1007/s10156-004-0348-9] [PMID: 15614453]
[6]
Bray, P.G.; Barrett, M.P.; Ward, S.A.; de Koning, H.P. Pentamidine uptake and resistance in pathogenic protozoa: Past, present and future. Trends Parasitol., 2003, 19(5), 232-239.
[http://dx.doi.org/10.1016/S1471-4922(03)00069-2] [PMID: 12763430]
[7]
Jung, H.J.; Suh, S.I.; Suh, M.H.; Baek, W.K.; Park, J.W. Pentamidine reduces expression of hypoxia-inducible factor-1α in DU145 and MDA-MB-231 cancer cells. Cancer Lett., 2011, 303(1), 39-46.
[http://dx.doi.org/10.1016/j.canlet.2011.01.008] [PMID: 21316841]
[8]
Dorlo, T.P.; Kager, P.A. Pentamidine dosage: A base/salt confusion. PLoS Negl. Trop. Dis., 2008, 2(5), e225.
[http://dx.doi.org/10.1371/journal.pntd.0000225] [PMID: 18509543]
[9]
Li, W.; Schäfer, A.; Kulkarni, S.S.; Liu, X.; Martinez, D.R.; Chen, C.; Sun, Z.; Leist, S.R.; Drelich, A.; Zhang, L.; Ura, M.L.; Berezuk, A.; Chittori, S.; Leopold, K.; Mannar, D.; Srivastava, S.S.; Zhu, X.; Peterson, E.C.; Tseng, C.T.; Mellors, J.W.; Falzarano, D.; Subramaniam, S.; Baric, R.S.; Dimitrov, D.S. High potency of a bivalent human VH domain in SARS-CoV-2 animal models. Cell, 2020, 183(2), 429-441.e16.
[http://dx.doi.org/10.1016/j.cell.2020.09.007] [PMID: 32941803]
[10]
Hassan, A.O.; Kafai, N.M.; Dmitriev, I.P.; Fox, J.M.; Smith, B.K.; Harvey, I.B.; Chen, R.E.; Winkler, E.S.; Wessel, A.W.; Case, J.B.; Kashentseva, E.; McCune, B.T.; Bailey, A.L.; Zhao, H.; VanBlargan, L.A.; Dai, Y.N.; Ma, M.; Adams, L.J.; Shrihari, S.; Danis, J.E.; Gralinski, L.E.; Hou, Y.J.; Schäfer, A.; Kim, A.S.; Keeler, S.P.; Weiskopf, D.; Baric, R.S.; Holtzman, M.J.; Fremont, D.H.; Curiel, D.T.; Diamond, M.S. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2. Cell, 2020, 183(1), 169-184.e13.
[http://dx.doi.org/10.1016/j.cell.2020.08.026] [PMID: 32931734]
[11]
Jha, T.K.; Sharma, V.K. Pentamidine-induced diabetes mellitus. Trans. R. Soc. Trop. Med. Hyg., 1984, 78(2), 252-253.
[http://dx.doi.org/10.1016/0035-9203(84)90289-X] [PMID: 6464116]
[12]
Murdoch, J.K. Pentamidine and hypoglycemia. Ann. Intern. Med., 1983, 99(6), 879.
[http://dx.doi.org/10.7326/0003-4819-99-6-879_1] [PMID: 6651038]
[13]
Leen, C.L.; Mandal, B.K. Rash due to nebulised pentamidine. Lancet, 1988, 2(8622), 1250-1251.
[http://dx.doi.org/10.1016/S0140-6736(88)90841-0] [PMID: 2903979]
[14]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[15]
Paul, M.; Durand, R.; Boulard, Y.; Fusaï, T.; Fernandez, C.; Rivollet, D.; Deniau, M.; Astier, A. Physicochemical characteristics of pentamidine-loaded polymethacrylate nanoparticles: implication in the intracellular drug release in Leishmania major infected mice. J. Drug Target., 1998, 5(6), 481-490.
[http://dx.doi.org/10.3109/10611869808997874] [PMID: 9783679]
[16]
Kramp, K.L.; DeWitt, K.; Flora, J.W.; Muddiman, D.C.; Slunt, K.M.; Houston, T.A. Derivatives of pentamidine designed to target the Leishmania lipophosphoglycan. Tetrahedron Lett., 2005, 46(4), 695-698.
[http://dx.doi.org/10.1016/j.tetlet.2004.11.112]
[17]
Clement, B.; Bürenheide, A.; Rieckert, W.; Schwarz, J. Diacetyldiamidoximeester of pentamidine, a prodrug for treatment of protozoal diseases: Synthesis, in vitro and in vivo biotransformation. ChemMedChem, 2006, 1(11), 1260-1267.
[http://dx.doi.org/10.1002/cmdc.200600079] [PMID: 17001612]
[18]
Mayer, C.D.; Bracher, F. Cytotoxic ring A-modified steroid analogues derived from Grundmann’s ketone. Eur. J. Med. Chem., 2011, 46(8), 3227-3236.
[http://dx.doi.org/10.1016/j.ejmech.2011.04.036] [PMID: 21570162]
[19]
Farahat, A.A.; Ismail, M.A.; Kumar, A.; Wenzler, T.; Brun, R.; Paul, A.; Wilson, W.D.; Boykin, D.W. Indole and benzimidazole bichalcophenes: Synthesis, DNA binding and antiparasitic activity. Eur. J. Med. Chem., 2018, 143, 1590-1596.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.056] [PMID: 29126729]
[20]
Duszenko, M.; Ferguson, M.A.; Lamont, G.S.; Rifkin, M.R.; Cross, G.A. Cysteine eliminates the feeder cell requirement for cultivation of Trypanosoma brucei bloodstream forms in vitro. J. Exp. Med., 1985, 162(4), 1256-1263.
[http://dx.doi.org/10.1084/jem.162.4.1256] [PMID: 4045385]
[21]
Sands, M.; Kron, M.A.; Brown, R.B. Pentamidine: A review. Rev. Infect. Dis., 1985, 7(5), 625-634.
[http://dx.doi.org/10.1093/clinids/7.5.625] [PMID: 3903942]
[22a]
a) Fusai, T.; Deniau, M.; Durand, R.; Bories, C.; Paul, M.; Rivollet, D.; Astier, A.; Houin, R. Action of pentamidine-bound nanoparticles against Leishmania on an in vivo model. Parasite, 1994, 1(4), 319-324.
[http://dx.doi.org/10.1051/parasite/1994014319] [PMID: 9140499]
b) Yorke W. Recent work on the chemotherapy of protozoal infections. Trans. R. Soc. Trop. Med. Hyg., 1940, 33(5), 463-476.
[http://dx.doi.org/10.1016/S0035-9203(40)90029-3]
[23]
Peretti, E.; Miletto, I.; Stella, B.; Rocco, F.; Berlier, G.; Arpicco, S. Strategies to obtain encapsulation and controlled release of pentamidine in mesoporous silica nanoparticles. Pharmaceutics, 2018, 10(4), E195.
[http://dx.doi.org/10.3390/pharmaceutics10040195] [PMID: 30347763]
[24]
Jannin, J.; Cattand, P. Treatment and control of human African trypanosomiasis. Curr. Opin. Infect. Dis., 2004, 17(6), 565-571.
[http://dx.doi.org/10.1097/00001432-200412000-00009] [PMID: 15640711]
[25]
Mathis, A.M.; Holman, J.L.; Sturk, L.M.; Ismail, M.A.; Boykin, D.W.; Tidwell, R.R.; Hall, J.E. Accumulation and intracellular distribution of antitrypanosomal diamidine compounds DB75 and DB820 in African trypanosomes. Antimicrob. Agents Chemother., 2006, 50(6), 2185-2191.
[http://dx.doi.org/10.1128/AAC.00192-06] [PMID: 16723581]
[26]
Lanteri, C.A.; Stewart, M.L.; Brock, J.M.; Alibu, V.P.; Meshnick, S.R.; Tidwell, R.R.; Barrett, M.P. Roles for the Trypanosoma brucei P2 transporter in DB75 uptake and resistance. Mol. Pharmacol., 2006, 70(5), 1585-1592.
[http://dx.doi.org/10.1124/mol.106.024653] [PMID: 16912218]
[27]
Gale, R.P.; Chapel, H.M.; Bunch, C.; Rai, K.R.; Foon, K.; Courter, S.G.; Tait, D. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. N. Engl. J. Med., 1988, 319(14), 902-907.
[http://dx.doi.org/10.1056/NEJM198810063191403] [PMID: 2901668]
[28]
Alston, T.A. Inhibition of cholinesterases by pentamidine. Lancet, 1988, 2(8625), 1423.
[http://dx.doi.org/10.1016/S0140-6736(88)90612-5] [PMID: 2904548]
[29]
Heley, A. Aerosolised pentamidine treatment at home. Lancet, 1987, 2(8567), 1092.
[http://dx.doi.org/10.1016/S0140-6736(87)91523-6] [PMID: 2890004]
[30]
Tanious, F.; Wilson, W.D.; Wang, L.; Kumar, A.; Boykin, D.W.; Marty, C.; Baldeyrou, B.; Bailly, C. Cooperative dimerization of a heterocyclic diamidine determines sequence-specific DNA recognition. Biochemistry, 2003, 42(46), 13576-13586.
[http://dx.doi.org/10.1021/bi034852y] [PMID: 14622004]
[31]
Laughlin, S.; Wang, S.; Kumar, A.; Farahat, A.A.; Boykin, D.W.; Wilson, W.D. Resolution of mixed site DNA complexes with dimer-forming minor-groove binders by using electrospray ionization mass spectrometry: Compound structure and DNA sequence effects. Chemistry, 2015, 21(14), 5528-5539.
[http://dx.doi.org/10.1002/chem.201406322] [PMID: 25703690]
[32]
Sánchez, M.I.; Vázquez, O.; Vázquez, M.E.; Mascareñas, J.L. Light-controlled DNA binding of bisbenzamidines. Chem. Commun. (Camb.), 2011, 47(39), 11107-11109.
[http://dx.doi.org/10.1039/c1cc13355a] [PMID: 21909542]
[33]
Berg, R.W.; Riisager, A.; Fehrmann, R. Formation of an ion-pair molecule with a single NH(+)...Cl(-) hydrogen bond: Raman spectra of 1,1,3,3-tetramethylguanidinium chloride in the solid state, in solution, and in the vapor phase. J. Phys. Chem. A, 2008, 112(37), 8585-8592.
[http://dx.doi.org/10.1021/jp803597j] [PMID: 18714951]
[34]
Lucas, J.M.S. The chemotherapy of experimental babesiasis in mice and splenectomized calves. Res. Vet. Sci., 1960, 1(3), 218-225.
[http://dx.doi.org/10.1016/S0034-5288(18)34999-3]
[35]
Ashley, J.N.; Berg, S.S.; Lucas, J.M. 3:3′-diamidinocarbanilide: a new drug active against Babesial infections. Nature, 1960, 185(4711), 461.
[http://dx.doi.org/10.1038/185461a0] [PMID: 18990808]
[36]
Worrell, B.T.; Malik, J.A.; Fokin, V.V. Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azide-alkyne cycloadditions. Science, 2013, 340(6131), 457-460.
[http://dx.doi.org/10.1126/science.1229506] [PMID: 23558174]
[37]
Scala, A.; Piperno, A.; Micale, N.; Mineo, P.G.; Abbadessa, A.; Risoluti, R.; Castelli, G.; Bruno, F.; Vitale, F.; Cascio, A.; Grassi, G. “Click” on PLGA-PEG and hyaluronic acid: Gaining access to anti-leishmanial pentamidine bioconjugates. J. Biomed. Mater. Res. B Appl. Biomater., 2018, 106(8), 2778-2785.
[http://dx.doi.org/10.1002/jbm.b.34058] [PMID: 29219244]
[38]
Young, L.S.; Rickinson, A.B. Epstein-Barr virus: 40 years on. Nat. Rev. Cancer, 2004, 4(10), 757-768.
[http://dx.doi.org/10.1038/nrc1452] [PMID: 15510157]
[39]
Wang, Y. B.; Peng, Y. H.; Zhang, B.; Zhang, X. Z.; Li, H. Y.; Wilson, A. J.; Mineev, K. S.; Wang, X. H. Targeting trimeric transmembrane domain 5 of oncogenic latent membrane protein 1 using a computationally designed peptide. Chem. Sci., 2019, 10(32), 7584-7590.
[http://dx.doi.org/10.1039/C9SC02474C]
[40]
Wang, X.; Saludes, J.P.; Zhao, T.X.; Csakai, A.; Fiorini, Z.; Chavez, S.A.; Li, J.; Lee, G.I.; Varga, K.; Yin, H. Targeting the lateral interactions of transmembrane domain 5 of Epstein-Barr virus latent membrane protein 1. Biochim. Biophys. Acta, 2012, 1818(9), 2282-2289.
[http://dx.doi.org/10.1016/j.bbamem.2012.05.013] [PMID: 22609737]
[41]
Sammond, D.W.; Joce, C.; Takeshita, R.; McQuate, S.E.; Ghosh, N.; Martin, J.M.; Yin, H. Transmembrane peptides used to investigate the homo-oligomeric interface and binding hotspot of latent membrane protein 1. Biopolymers, 2011, 95(11), 772-784.
[http://dx.doi.org/10.1002/bip.21672] [PMID: 21560118]
[42]
Zhang, B.; Wang, Y.; Lin, C.; Li, H.; Wang, X.; Peng, Y.; Mineev, K.S.; Wilson, A.J.; Wang, H.; Wang, X. Targeting the transmembrane domain 5 of latent membrane protein 1 using small molecule modulators. Eur. J. Med. Chem., 2021, 214, 113210.
[http://dx.doi.org/10.1016/j.ejmech.2021.113210] [PMID: 33550183]
[43]
Scott, C.; Griffin, S. Viroporins: structure, function and potential as antiviral targets. J. Gen. Virol., 2015, 96(8), 2000-2027.
[http://dx.doi.org/10.1099/vir.0.000201] [PMID: 26023149]
[44]
Singh Tomar, P.P.; Arkin, I.T. SARS-CoV-2 E protein is a potential ion channel that can be inhibited by Gliclazide and Memantine. Biochem. Biophys. Res. Commun., 2020, 530(1), 10-14.
[http://dx.doi.org/10.1016/j.bbrc.2020.05.206] [PMID: 32828269]
[45]
Tomar, P.P.S.; Krugliak, M.; Arkin, I.T. Blockers of the SARS-CoV-2 3a channel identified by targeted drug repurposing. Viruses, 2021, 13(3), 532.
[http://dx.doi.org/10.3390/v13030532] [PMID: 33807095]

Rights & Permissions Print Cite
Article Metrics
29
1
© 2024 Bentham Science Publishers | Privacy Policy