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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Review Article

Selective Estrogen Receptor Modulators (SERMs): Mechanistic Insights Against Microbial Infections

Author(s): Aakriti Garg, Balraj Singh, Ruchika Sharma, Arti Singh and Anoop Kumar*

Volume 20, Issue 2, 2020

Page: [102 - 115] Pages: 14

DOI: 10.2174/1566524019666191014112133

Price: $65

Abstract

Background: Infections are one of the leading causes of death worldwide and currently available treatments remain unsatisfactory due to rise in the cases of antimicrobial resistance. Thus, there is a need for the development of new drugs with different mechanisms of action. However, the development of new antimicrobials agents is a long and expensive process. Hence, most of the pharmaceutical companies are looking forward to repurposing the already available drugs against microbial infections.

Methodology: The data related to SERMs and microbial infection has been extracted from Pub Med (from January 1997 to December 2018). A total of 101 studies have been published from 1997 -2018 regarding SERMs and microbial infections.

Results: On the basis of inclusion and exclusion criteria, 25 studies have been included for the analysis of level of evidence regarding antimicrobial effects of SERMs. Emerging reports have indicated the antimicrobial property of selective estrogen receptor modulators (SERMs) against normal and resistant strains under in vitro and in vivo conditions against wide variety of microorganisms through different mechanisms of action.

Conclusion: In conclusion, SERMs could be developed as a broad spectrum antimicrobial agent alone or in combination with existing antimicrobial agents.

Keywords: SERMs, drug repurposing, drug resistance, antimicrobial activity, microbial infections, estrogen.

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[1]
Rathi B, Latha N, Faletrov Y, Bhargava P, Shkumatov V. EDITORIAL: New avenues in controlling infectious diseases. Curr Top Med Chem 2017; 17(19): 2113.
[http://dx.doi.org/10.2174/156802661719170616164549] [PMID: 28664823]
[2]
Khan HA, Baig FK, Mehboob R. Nosocomial infections: Epidemiology, prevention, control and surveillance. Asian Pac J Trop Biomed 2017; 7(5): 478-82.
[http://dx.doi.org/10.1016/j.apjtb.2017.01.019]
[3]
Sanders JW, Fuhrer GS, Johnson MD, Riddle MS. The epidemiological transition: the current status of infectious diseases in the developed world versus the developing world. Sci Prog 2008; 91(Pt 1): 1-37.
[http://dx.doi.org/10.3184/003685008X284628] [PMID: 18453281]
[4]
Ambrus JL Sr, Ambrus JL Jr. Nutrition and infectious diseases in developing countries and problems of acquired immunodeficiency syndrome. Exp Biol Med (Maywood) 2004; 229(6): 464-72.
[http://dx.doi.org/10.1177/153537020422900603] [PMID: 15169964]
[5]
De Lamballerie X, Colson P. The battle against infectious diseases in developing countries: the inseparable twins of diagnosis and therapy. Clin Chem 2006; 52(7): 1217-7.
[http://dx.doi.org/10.1373/clinchem.2006.071316]
[6]
Bhutta ZA, Salam RA, Das JK, Lassi ZS. Tackling the existing burden of infectious diseases in the developing world: existing gaps and the way forward. Infect Dis Poverty 2014; 3(1): 28.
[http://dx.doi.org/10.1186/2049-9957-3-28] [PMID: 25105015]
[7]
Bassetti M, Vena A, Croxatto A, Righi E, Guery B. How to manage Pseudomonas aeruginosa infections. Drugs Context 2018; 7: 212527
[http://dx.doi.org/10.7573/dic.212527] [PMID: 29872449]
[8]
Rayner C, Munckhof WJ. Antibiotics currently used in the treatment of infections caused by Staphylococcus aureus. Intern Med J 2005; 35(Suppl. 2): S3-S16.
[http://dx.doi.org/10.1111/j.1444-0903.2005.00976.x] [PMID: 16271060]
[9]
Rappuoli R, Bloom DE, Black S. Deploy vaccines to fight superbugs. Nature 2017; 14; 552(7684): 165-7.
[http://dx.doi.org/10.1038/d41586-017-08323-0]
[10]
World Health Organization (WHO); Antimicrobial resistance Geneva, Switzerland: WHO.Available at: .. http://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance [accessed November 12, 2018].
[11]
Rana R, Sharma R, Kumar A. Repurposing of existing statin drugs for treatment of microbial infections: how much promising? Infect Disord Drug Targets 2019; 19(3): 224-37.
[http://dx.doi.org/10.2174/1871526518666180806123230] [PMID: 30081793]
[12]
Corsello SM, Bittker JA, Liu Z, et al. The Drug Repurposing Hub: a next-generation drug library and information resource. Nat Med 2017; 23(4): 405-8.
[http://dx.doi.org/10.1038/nm.4306] [PMID: 28388612]
[13]
Kapoor Y, Sharma R, Kumar A. Repurposing of existing drugs for the bacterial infections: An In silico and In vitro study. Infect Disord Drug Targets 2018. Epub ahead of print
[http://dx.doi.org/10.2174/1871526519666181126094244] [PMID: 30474540]
[14]
Rana R, Sharma R, Kumar A. Repurposing of Fluvastatin against Candida albicans CYP450 lanosterol 14 α-demethylase, a target enzyme for antifungal therapy: An In silico and In vitro study. Curr Mol Med 2019; 19(7): 506-24.
[http://dx.doi.org/10.2174/1566524019666190520094644] [PMID: 31109273]
[15]
Gupta M, Sharma R, Kumar A. Comparative potential of Simvastatin, Rosuvastatin and Fluvastatin against bacterial infection: an in silico and in vitro study. Orient Pharm Exp Med 2019; 19: 259-75.
[http://dx.doi.org/10.1007/s13596-019-00359-z]
[16]
Xu B, Lovre D, Mauvais-Jarvis F. The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights. J Diabetes Complications 2017; 31(4): 773-9.
[http://dx.doi.org/10.1016/j.jdiacomp.2016.12.010] [PMID: 28185712]
[17]
Barreto GE, Santos-Galindo M, Garcia-Segura LM. Selective estrogen receptor modulators regulate reactive microglia after penetrating brain injury. Front Aging Neurosci 2014; 6: 132.
[http://dx.doi.org/10.3389/fnagi.2014.00132] [PMID: 24999330]
[18]
Christodoulakos GE, Lambrinoudaki IV, Botsis DC. The cardiovascular effects of selective estrogen receptor modulators. Ann N Y Acad Sci 2006; 1092(1): 374-84.
[http://dx.doi.org/10.1196/annals.1365.034] [PMID: 17308162]
[19]
Hussein MH, Schneider EK, Elliott AG, et al. From breast cancer to antimicrobial: combating extremely resistant Gram-negative “superbugs” using novel combinations of polymyxin B with selective estrogen receptor modulators. Microb Drug Resist 2017; 23(5): 640-50.
[http://dx.doi.org/10.1089/mdr.2016.0196] [PMID: 27935770]
[20]
Ho Sui SJ, Lo R, Fernandes AR, et al. Raloxifene attenuates Pseudomonas aeruginosa pyocyanin production and virulence. Int J Antimicrob Agents 2012; 40(3): 246-51.
[http://dx.doi.org/10.1016/j.ijantimicag.2012.05.009] [PMID: 22819149]
[21]
Sun W, He S, Martínez-Romero C, et al. Synergistic drug combination effectively blocks Ebola virus infection. Antiviral Res 2017; 137: 165-72.
[http://dx.doi.org/10.1016/j.antiviral.2016.11.017] [PMID: 27890675]
[22]
Gerits E, Defraine V, Vandamme K, et al. Repurposing toremifene for treatment of oral bacterial infections. Antimicrob Agents Chemother 2017; 61(3): e01846-16.
[http://dx.doi.org/10.1128/AAC.01846-16] [PMID: 27993858]
[23]
De Cremer K, Delattin N, De Brucker K, et al. Oral administration of the broad-spectrum antibiofilm compound toremifene inhibits Candida albicans and Staphylococcus aureus biofilm formation in vivo. Antimicrob Agents Chemother 2014; 58(12): 7606-10.
[http://dx.doi.org/10.1128/AAC.03869-14] [PMID: 25288093]
[24]
Doroodgar M, Delavari M, Doroodgar M, Abbasi A, Taherian AA, Doroodgar A. Tamoxifen induces apoptosis of Leishmania major promastigotes in vitro. Korean J Parasitol 2016; 54(1): 9-14.
[http://dx.doi.org/10.3347/kjp.2016.54.1.9] [PMID: 26951973]
[25]
Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 2012; 125(1)(Suppl.): S3-S13.
[http://dx.doi.org/10.1016/j.amjmed.2011.11.001] [PMID: 22196207]
[26]
Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. P&T 2015; 40(4): 277-83.
[PMID: 25859123]
[27]
Berkow EL, Lockhart SR. Fluconazole resistance in Candida species: a current perspective. Infect Drug Resist 2017; 10: 237-45.
[http://dx.doi.org/10.2147/IDR.S118892] [PMID: 28814889]
[28]
Jiang YC, Feng H, Lin YC, Guo XR. New strategies against drug resistance to herpes simplex virus. Int J Oral Sci 2016; 8(1): 1-6.
[http://dx.doi.org/10.1038/ijos.2016.3] [PMID: 27025259]
[29]
Ouellette M. Biochemical and molecular mechanisms of drug resistance in parasites. Trop Med Int Health 2001; 6(11): 874-82.
[http://dx.doi.org/10.1046/j.1365-3156.2001.00777.x] [PMID: 11703841]
[30]
Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectr 2016; 4(2): 10.
[PMID: 27227291]
[31]
Delcour AH. Outer membrane permeability and antibiotic resistance. Biochim Biophys Acta 2009; 1794(5): 808-16.
[http://dx.doi.org/10.1016/j.bbapap.2008.11.005] [PMID: 19100346]
[32]
Fernández L, Hancock RE. Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev 2012; 25(4): 661-81.
[http://dx.doi.org/10.1128/CMR.00043-12] [PMID: 23034325]
[33]
Singh S, Singh SK, Chowdhury I, Singh R. Understanding the mechanism of bacterial biofilms resistance to antimicrobial agents. Open Microbiol J 2017; 11: 53-62.
[http://dx.doi.org/10.2174/1874285801711010053] [PMID: 28553416]
[34]
Montealegre MC, Roh JH, Rae M, et al. Differential penicillin-binding protein 5 (PBP5) levels in the Enterococcus faecium clades with different levels of ampicillin resistance. Antimicrob Agents Chemother 2016; 61(1): e02034-16.
[PMID: 27821450]
[35]
Food and Drug Administration (FDA). Drugs@FDA: FDA Approved Drug Products. Available at: . https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=017970 [accessed December 10, 2018].
[36]
electronic Medicines Compendium (eMC). Tamoxifen 20mg Film-Coated Tablets. Available at:. . https://www.medicines.org.uk/emc/product/2248/smpc 20updated on 10 August 2018 [accessed November 15, 2018].18
[37]
Food and Drug Administration (FDA). Drugs@FDA: FDA Approved Drug Products. Available at:.. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020497 [accessed December 10, 2018].
[38]
Food and Drug Administration (FDA). Drugs@FDA: FDA Approved Drug Products. Available at:. . https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020815 [accessed December 10, 2018].
[39]
electronic Medicines Compendium (eMC). Fareston 60mg Tablets. Available at:. . https://www.medicines.org.uk/emc/product/1705/smpc updated on 28 June 2017 [accessed December 11, 2018].
[40]
electronic Medicines Compendium (eMC). Evista 60mg filmcoated tablets. Available at:. . https://www.medicines.org.uk/emc/product/3778/smpc updated on 23 October 2017 [accessed December 11, 2018].
[41]
Qin T, Yuan ZY, Peng RJ, et al. Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer: a retrospective analysis. Curr Oncol 2013; 20(4): 196-204.
[http://dx.doi.org/10.3747/co.20.1231] [PMID: 23904760]
[42]
D’Amelio P, Isaia GC. The use of raloxifene in osteoporosis treatment. Expert Opin Pharmacother 2013; 14(7): 949-56.
[http://dx.doi.org/10.1517/14656566.2013.782002] [PMID: 23521229]
[43]
Morello KC, Wurz GT, DeGregorio MW. Pharmacokinetics of selective estrogen receptor modulators. Clin Pharmacokinet 2003; 42(4): 361-72.
[http://dx.doi.org/10.2165/00003088-200342040-00004] [PMID: 12648026]
[44]
Farrar MC, Jacobs TF. Tamoxifen.StatPearls. Treasure Island, FL: StatPearls Publishing 2019.https://www.ncbi.nlm.nih.gov/books/NBK532905/ Updated 2018 Dec 29 Internet
[45]
Toremifene-Indication, dosage, side effects, and precautions. Available at:. . https://www.medindia.net/doctors/drug_information/toremifene.htm [accessed 23August 2019].
[46]
Who should not take raloxifene HCl? Available at:. . https://www.webmd.com/drugs/2/drug-5191/raloxifene-oral/details/list-contraindications [accessed on 23 August 2019].
[47]
El Arbi M, Théolier J, Pigeon P, et al. Antibacterial properties and mode of action of new triaryl butene citrate compounds. Eur J Med Chem 2014; 76: 408-13.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.037] [PMID: 24602786]
[48]
Jang WS, Kim S, Podder B, et al. Anti-mycobacterial activity of tamoxifen against drug-resistant and intra-macrophage Mycobacterium tuberculosis. J Microbiol Biotechnol 2015; 25(6): 946-50.
[http://dx.doi.org/10.4014/jmb.1412.12023] [PMID: 25639719]
[49]
Tisi R, Rigamonti M, Groppi S, Belotti F. Calcium homeostasis and signaling in fungi and their relevance for pathogenicity of yeasts and filamentous fungi. AIMS Mol Sci 2016; 3(4): 505-49.
[http://dx.doi.org/10.3934/molsci.2016.4.505]
[50]
Reimão JQ, Miguel DC, Taniwaki NN, Trinconi CT, Yokoyama-Yasunaka JK, Uliana SR. Antileishmanial activity of the estrogen receptor modulator raloxifene. PLoS Negl Trop Dis 2014; 8: (5) e2842
[http://dx.doi.org/10.1371/journal.pntd.0002842] [PMID: 24810565]
[51]
Dittmar AJ, Drozda AA, Blader IJ. Drug repurposing screening identifies novel compounds that effectively inhibit Toxoplasma gondii growth. MSphere 2016; 1(2): e00042-15.
[http://dx.doi.org/10.1128/mSphere.00042-15] [PMID: 27303726]
[52]
Johansen LM, Brannan JM, Delos SE, et al. FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection. Sci Transl Med 2013; 5(190)190ra79
[http://dx.doi.org/10.1126/scitranslmed.3005471] [PMID: 23785035]
[53]
Zhao Y, Ren J, Harlos K, et al. Toremifene interacts with and destabilizes the Ebola virus glycoprotein. Nature 2016; 535(7610): 169-72.
[http://dx.doi.org/10.1038/nature18615] [PMID: 27362232]
[54]
Zheng K, Chen M, Xiang Y, et al. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB. Biochem Biophys Res Commun 2014; 446(4): 990-6.
[http://dx.doi.org/10.1016/j.bbrc.2014.03.050] [PMID: 24657267]
[55]
Kamboj A, Randhawa H. Pharmacological action and sar of thiophene derivatives: A review. J Pharm Res 2012; 5(5): 2676-82.
[56]
Delattin N, De Brucker K, Vandamme K, et al. Repurposing as a means to increase the activity of amphotericin B and caspofungin against Candida albicans biofilms. J Antimicrob Chemother 2014; 69(4): 1035-44.
[http://dx.doi.org/10.1093/jac/dkt449] [PMID: 24284780]
[57]
Butts A, Koselny K, Chabrier-Roselló Y, et al. Estrogen receptor antagonists are anti-cryptococcal agents that directly bind EF hand proteins and synergize with fluconazole in vivo. MBio 2014; 5(1): e00765-13.
[http://dx.doi.org/10.1128/mBio.00765-13] [PMID: 24520056]
[58]
Trinconi CT, Reimão JQ, Yokoyama-Yasunaka JK, Miguel DC, Uliana SR. Combination therapy with tamoxifen and amphotericin B in experimental cutaneous leishmaniasis. Antimicrob Agents Chemother 2014; 58(5): 2608-13.
[http://dx.doi.org/10.1128/AAC.01315-13] [PMID: 24550333]
[59]
Miguel DC, Zauli-Nascimento RC, Yokoyama-Yasunaka JK, Katz S, Barbiéri CL, Uliana SR. Tamoxifen as a potential antileishmanial agent: efficacy in the treatment of Leishmania braziliensis and Leishmania chagasi infections. J Antimicrob Chemother 2009; 63(2): 365-8.
[http://dx.doi.org/10.1093/jac/dkn509] [PMID: 19095684]
[60]
Eissa MM, Amer EI, El Sawy SM. Leishmania major: activity of tamoxifen against experimental cutaneous leishmaniasis. Exp Parasitol 2011; 128(4): 382-90.
[http://dx.doi.org/10.1016/j.exppara.2011.05.009] [PMID: 21620834]
[61]
Escobedo G, Palacios-Arreola MI, Olivos A, López-Griego L, Morales-Montor J. Tamoxifen treatment in hamsters induces protection during taeniosis by Taenia solium. Biomed Res Int 2012; 2013: 280496
[62]
Cong Y, Hart BJ, Gross R, et al. MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells. PLoS One 2018; 13(3)e0194868
[http://dx.doi.org/10.1371/journal.pone.0194868] [PMID: 29566060]
[63]
Wang LL, Chen Q, Zhou LN, Guo Y. [Study of gonadal hormone drugs in blocking filovirus entry of cells in vitro]. Yao Xue Xue Bao. 2015; 50(12): 1545-50.
[PMID: 27169275]
[64]
Dyall J, Nelson EA, DeWald LE, et al. Identification of combinations of approved drugs with synergistic activity against Ebola virus in cell cultures J Infect Dis 2018; 25(suppl_5): S672-8.
[65]
Furusyo N, Ogawa E, Sudoh M, et al. Raloxifene hydrochloride is an adjuvant antiviral treatment of postmenopausal women with chronic hepatitis C: a randomized trial. J Hepatol 2012; 57(6): 1186-92.
[http://dx.doi.org/10.1016/j.jhep.2012.08.003] [PMID: 22889955]
[66]
Miguel DC, Yokoyama-Yasunaka JK, Uliana SR. Tamoxifen is effective in the treatment of Leishmania amazonensis infections in mice. PLoS Negl Trop Dis 2008; 2(6)e249
[http://dx.doi.org/10.1371/journal.pntd.0000249] [PMID: 18545685]
[67]
Trinconi CT, Reimão JQ, Coelho AC, Uliana SR. Efficacy of tamoxifen and miltefosine combined therapy for cutaneous leishmaniasis in the murine model of infection with Leishmania amazonensis. J Antimicrob Chemother 2016; 71(5): 1314-22.
[http://dx.doi.org/10.1093/jac/dkv495] [PMID: 26851606]
[68]
Dolan K, Montgomery S, Buchheit B, Didone L, Wellington M, Krysan DJ. Antifungal activity of tamoxifen: in vitro and in vivo activities and mechanistic characterization. Antimicrob Agents Chemother 2009; 53(8): 3337-46.
[http://dx.doi.org/10.1128/AAC.01564-08] [PMID: 19487443]

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