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Volume 25, Issue 3
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

This review article delves into the critical role of Enoyl acyl carrier protein reductase (InhA; ENR), a vital enzyme in the NADH-dependent acyl carrier protein reductase family, emphasizing its significance in fatty acid synthesis and, more specifically, the biosynthesis of mycolic acid. The primary objective of this literature review is to elucidate diverse scaffolds and their developmental progression targeting InhA inhibition, thereby disrupting mycolic acid biosynthesis. Various scaffolds, including thiourea, piperazine, thiadiazole, triazole, quinazoline, benzamide, rhodanine, benzoxazole, and pyridine, have been systematically explored for their potential as InhA inhibitors. Noteworthy findings highlight thiadiazole and triazole derivatives, demonstrating promising IC values within the nanomolar concentration range. The review offers comprehensive insights into InhA's structure, structure-activity relationships, and a detailed overview of distinct scaffolds as effective inhibitors of InhA.

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2025-01-15

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References

  1. PrasadM.S. BholeR.P. KhedekarP.B. ChikhaleR.V. Mycobacterium enoyl acyl carrier protein reductase (InhA): A key target for antitubercular drug discovery.Bioorg. Chem.202111510524210.1016/j.bioorg.2021.105242 34392175
     [Google Scholar]
  2. JeeB. Understanding the early host immune response against Mycobacterium tuberculosis.Cent. Eur. J. Immunol.20204519910310.5114/ceji.2020.94711 32425687
     [Google Scholar]
  3. BurkiT. Tuberculosis mortality targets off-track.Lancet Infect. Dis.201919547210.1016/S1473‑3099(19)30179‑3 31034394
     [Google Scholar]
  4. LinC.H. LinC.J. KuoY.W. WangJ.Y. HsuC.L. ChenJ.M. ChengW.C. LeeL.N. Tuberculosis mortality: Patient characteristics and causes.BMC Infect. Dis.2014141510.1186/1471‑2334‑14‑5 24387757
     [Google Scholar]
  5. DenholmJ.T. MaraisB.J. DonnanE.J. WaringJ. StapledonR. TaylorJ.W. MahantyS. Tuberculosis mortality: Quantifying agreement in clinical cause of death assessments.Aust. N. Z. J. Public Health202246563063210.1111/1753‑6405.13204 35436020
     [Google Scholar]
  6. MacNeilA. GlaziouP. SismanidisC. DateA. MaloneyS. FloydK. Global epidemiology of tuberculosis and progress toward meeting global targets — Worldwide, 2018.MMWR Morb. Mortal. Wkly. Rep.2020691128128510.15585/mmwr.mm6911a2 32191687
     [Google Scholar]
  7. FukunagaR. GlaziouP. HarrisJ.B. DateA. FloydK. KasaevaT. Epidemiology of tuberculosis and progress toward meeting global targets — Worldwide, 2019.MMWR Morb. Mortal. Wkly. Rep.2021701242743010.15585/mmwr.mm7012a4 33764960
     [Google Scholar]
  8. GlaziouP. SismanidisC. FloydK. RaviglioneM. Global epidemiology of tuberculosis.Cold Spring Harb. Perspect. Med.201552a01779810.1101/cshperspect.a017798 25359550
     [Google Scholar]
  9. SloanD. DaviesG. KhooS. Recent advances in tuberculosis: New drugs and treatment regimens.Curr. Respir. Med. Rev.20139320021010.2174/1573398X113099990017 24683386
     [Google Scholar]
  10. ShehzadA. RehmanG. Ul-IslamM. KhattakW.A. LeeY.S. Challenges in the development of drugs for the treatment of tuberculosis.Braz. J. Infect. Dis.2013171748110.1016/j.bjid.2012.10.009 23287547
     [Google Scholar]
  11. UddinT.M. ChakrabortyA.J. KhusroA. ZidanB.M.R.M. MitraS. EmranT.B. DhamaK. RiponM.K.H. GajdácsM. SahibzadaM.U.K. HossainM.J. KoiralaN. Antibiotic resistance in microbes: History, mechanisms, therapeutic strategies and future prospects.J. Infect. Public Health202114121750176610.1016/j.jiph.2021.10.02034756812
     [Google Scholar]
  12. MacNairC.R. TsaiC.N. RutherfordS.T. TanM.W. returning to nature for the next generation of antimicrobial therapeutics.Antibiotics (Basel)2023128126710.3390/antibiotics12081267 37627687
     [Google Scholar]
  13. MeirellesL.A. PerryE.K. BergkesselM. NewmanD.K. Bacterial defenses against a natural antibiotic promote collateral resilience to clinical antibiotics.PLoS Biol.2021193e300109310.1371/journal.pbio.3001093 33690640
     [Google Scholar]
  14. SeungK.J. KeshavjeeS. RichM.L. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis.Cold Spring Harb. Perspect. Med.201559a01786310.1101/cshperspect.a017863 25918181
     [Google Scholar]
  15. TiberiS. ZumlaA. MiglioriG.B. multidrug and extensively drug-resistant tuberculosis.Infect. Dis. Clin. North Am.20193341063108510.1016/j.idc.2019.09.002 31668191
     [Google Scholar]
  16. MaitreT. AubryA. JarlierV. RobertJ. VezirisN. BernardC. SougakoffW. BrossierF. CambauE. MougariF. RaskineL. Multidrug and extensively drug-resistant tuberculosis.Med. Mal. Infect.201747131010.1016/j.medmal.2016.07.006 27637852
     [Google Scholar]
  17. AlsayedS.S.R. GunosewoyoH. Tuberculosis: Pathogenesis, current treatment regimens and new drug targets.Int. J. Mol. Sci.2023246520210.3390/ijms24065202 36982277
     [Google Scholar]
  18. PeloquinC.A. DaviesG.R. The treatment of tuberculosis.Clin. Pharmacol. Ther.202111061455146610.1002/cpt.2261 33837535
     [Google Scholar]
  19. PontaliE. RaviglioneM.C. MiglioriG.B. Regimens to treat multidrug-resistant tuberculosis: Past, present and future perspectives.Eur. Respir. Rev.20192815219003510.1183/16000617.0035‑2019 31142549
     [Google Scholar]
  20. TiberiS. du PlessisN. WalzlG. VjechaM.J. RaoM. NtoumiF. MfinangaS. KapataN. MwabaP. McHughT.D. IppolitoG. MiglioriG.B. MaeurerM.J. ZumlaA. Tuberculosis: Progress and advances in development of new drugs, treatment regimens, and host-directed therapies.Lancet Infect. Dis.2018187e183e19810.1016/S1473‑3099(18)30110‑5 29580819
     [Google Scholar]
  21. AlderwickL.J. HarrisonJ. LloydG.S. BirchH.L. The Mycobacterial cell wall—peptidoglycan and arabinogalactan.Cold Spring Harb. Perspect. Med.201558a02111310.1101/cshperspect.a021113 25818664
     [Google Scholar]
  22. AbrahamsK.A. BesraG.S. Mycobacterial cell wall biosynthesis: A multifaceted antibiotic target.Parasitology2018145211613310.1017/S0031182016002377 27976597
     [Google Scholar]
  23. JankuteM. CoxJ.A.G. HarrisonJ. BesraG.S. Assembly of the mycobacterial cell wall.Annu. Rev. Microbiol.201569140542310.1146/annurev‑micro‑091014‑104121 26488279
     [Google Scholar]
  24. XuX. DongB. PengL. GaoC. HeZ. WangC. ZengJ. Anti-tuberculosis drug development via targeting the cell envelope of Mycobacterium tuberculosis.Front. Microbiol.202213105660810.3389/fmicb.2022.1056608 36620019
     [Google Scholar]
  25. KumarN. SrivastavaR. MongreR.K. MishraC.B. KumarA. KhatoonR. BanerjeeA. Ashraf-Uz-ZamanM. SinghH. LynnA.M. LeeM.S. PrakashA. identifying the novel inhibitors against the mycolic acid biosynthesis pathway target “mtfabh” of Mycobacterium tuberculosis.Front. Microbiol.20221381871410.3389/fmicb.2022.818714 35602011
     [Google Scholar]
  26. ShetyeG.S. FranzblauS.G. ChoS. New tuberculosis drug targets, their inhibitors, and potential therapeutic impact.Transl. Res.2020220689710.1016/j.trsl.2020.03.007
     [Google Scholar]
  27. SmithS. WitkowskiA. JoshiA.K. Structural and functional organization of the animal fatty acid synthase.Prog. Lipid Res.200342428931710.1016/S0163‑7827(02)00067‑X 12689621
     [Google Scholar]
  28. CampbellJ.W. CronanJ.E.Jr Bacterial fatty acid biosynthesis: Targets for antibacterial drug discovery.Annu. Rev. Microbiol.200155130533210.1146/annurev.micro.55.1.305 11544358
     [Google Scholar]
  29. HeathR.J. RockC.O. Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli.J. Biol. Chem.199527044265382654210.1074/jbc.270.44.26538 7592873
     [Google Scholar]
  30. MagnusonK. JackowskiS. RockC.O. CronanJ.E.Jr Regulation of fatty acid biosynthesis in Escherichia coli.Microbiol. Rev.199357352254210.1128/mr.57.3.522‑542.1993 8246839
     [Google Scholar]
  31. HeathR.J. WhiteS.W. RockC.O. Lipid biosynthesis as a target for antibacterial agents.Prog. Lipid Res.200140646749710.1016/S0163‑7827(01)00012‑1 11591436
     [Google Scholar]
  32. HeathR.J. LiJ. RolandG.E. RockC.O. Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene.J. Biol. Chem.200027574654465910.1074/jbc.275.7.4654 10671494
     [Google Scholar]
  33. DessenA. QuémardA. BlanchardJ.S. JacobsW.R.Jr SacchettiniJ.C. Crystal structure and function of the isoniazid target of Mycobacterium tuberculosis.Science199526752041638164110.1126/science.7886450 7886450
     [Google Scholar]
  34. ParkH.S. YoonY.M. JungS.J. YunI.N.R. KimC.M. KimJ.M. KwakJ.H. CG400462, a new bacterial enoyl–acyl carrier protein reductase (FabI) inhibitor.Int. J. Antimicrob. Agents200730544645110.1016/j.ijantimicag.2007.07.006 17723291
     [Google Scholar]
  35. RoujeinikovaA. LevyC.W. RowsellS. SedelnikovaS. BakerP.J. MinshullC.A. MistryA. CollsJ.G. CambleR. StuitjeA.R. SlabasA.R. RaffertyJ.B. PauptitR.A. VinerR. RiceD.W. Crystallographic analysis of triclosan bound to enoyl reductase.J. Mol. Biol.1999294252753510.1006/jmbi.1999.3240 10610777
     [Google Scholar]
  36. CholletA. MoureyL. LherbetC. DelbotA. JulienS. BaltasM. BernadouJ. PratvielG. MaveyraudL. Bernardes-GénissonV. Crystal structure of the enoyl-ACP reductase of Mycobacterium tuberculosis (InhA) in the apo-form and in complex with the active metabolite of isoniazid pre-formed by a biomimetic approach.J. Struct. Biol.2015190332833710.1016/j.jsb.2015.04.008 25891098
     [Google Scholar]
  37. TongeP. KiskerC. SlaydenR. Development of modern InhA inhibitors to combat drug resistant strains of Mycobacterium tuberculosis.Curr. Top. Med. Chem.20077548949810.2174/156802607780059781 17346194
     [Google Scholar]
  38. MatviiukT. RodriguezF. SaffonN. Mallet-LadeiraS. GorichkoM. de Jesus Lopes RibeiroA.L. PascaM.R. LherbetC. VoitenkoZ. BaltasM. Design, chemical synthesis of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives and biological activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis.Eur. J. Med. Chem.201370374810.1016/j.ejmech.2013.09.041 24140915
     [Google Scholar]
  39. LucknerS.R. LiuN. am EndeC.W. TongeP.J. KiskerC. A slow, tight binding inhibitor of InhA, the enoyl-acyl carrier protein reductase from Mycobacterium tuberculosis.J. Biol. Chem.201028519143301433710.1074/jbc.M109.090373 20200152
     [Google Scholar]
  40. KumarV. SobhiaM.E. Insights into the bonding pattern for characterizing the open and closed state of the substrate-binding loop in Mycobacterium tuberculosis InhA.Future Med. Chem.20146660561610.4155/fmc.14.27 24895891
     [Google Scholar]
  41. KumarV. SobhiaM.E. Characterisation of the flexibility of substrate binding loop in the binding of direct InhA inhibitors.Int. J. Comput. Biol. Drug Des.20136431834210.1504/IJCBDD.2013.056795 24088266
     [Google Scholar]
  42. BonnacL. GaoG.Y. ChenL. FelczakK. BennettE.M. XuH. KimT. LiuN. OhH. TongeP.J. PankiewiczK.W. Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis.Bioorg. Med. Chem. Lett.200717164588459110.1016/j.bmcl.2007.05.084 17560106
     [Google Scholar]
  43. LuX.Y. YouQ.D. ChenY.D. Recent progress in the identification and development of InhA direct inhibitors of Mycobacterium tuberculosis.Mini Rev. Med. Chem.201010318219310.2174/138955710791185064 20408801
     [Google Scholar]
  44. SabbahM. MendesV. VistalR.G. DiasD.M.G. ZáhorszkáM. MikušováK. KordulákováJ. CoyneA.G. BlundellT.L. AbellC. Fragment-based design of Mycobacterium tuberculosis InhA inhibitors.J. Med. Chem.20206394749476110.1021/acs.jmedchem.0c00007 32240584
     [Google Scholar]
  45. EgbujorM.C. PetrosinoM. ZuhraK. SasoL. the role of organosulfur compounds as nrf2 activators and their antioxidant effects.Antioxidants2022117125510.3390/antiox11071255 35883746
     [Google Scholar]
  46. SharmaV. KaurB. SinghG. SinghI. Sulphur containing heterocyclic compounds as anticancer agents.Anticancer. Agents Med. Chem.202323886988110.2174/1871520623666221221143918 36545721
     [Google Scholar]
  47. KrátkyM. VinsovaJ. Sulphur-Containing Heterocycles as Antimycobacterial agents: Recent advances in thiophene and thiadiazole derivatives.Curr. Top. Med. Chem.201616262921295210.2174/1568026616666160506131118 27150373
     [Google Scholar]
  48. ShakeelA. Ataf Ali AltafA.A. QureshiA.M. BadshahA. Thiourea derivatives in drug design and medicinal chemistry: A Short Review.JDDMC2016211010.11648/j.jddmc.20160201.12
     [Google Scholar]
  49. PhetsuksiriB. JacksonM. SchermanH. McNeilM. BesraG.S. BaulardA.R. SlaydenR.A. DeBarberA.E. BarryC.E.III BairdM.S. CrickD.C. BrennanP.J. Unique mechanism of action of the thiourea drug isoxyl on Mycobacterium tuberculosis.J. Biol. Chem.200327852531235313010.1074/jbc.M311209200 14559907
     [Google Scholar]
  50. GrzegorzewiczA.E. EynardN. QuémardA. NorthE.J. MargolisA. LindenbergerJ.J. JonesV. KordulákováJ. BrennanP.J. LeeR.E. RonningD.R. McNeilM.R. JacksonM. Covalent modification of the Mycobacterium tuberculosis FAS-II dehydratase by Isoxyl and Thiacetazone.ACS Infect. Dis.201512919710.1021/id500032q 25897434
     [Google Scholar]
  51. DoğanŞ.D. GündüzM.G. DoğanH. KrishnaV.S. LherbetC. SriramD. Design and synthesis of thiourea-based derivatives as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors.Eur. J. Med. Chem.202019911240210.1016/j.ejmech.2020.112402 32417538
     [Google Scholar]
  52. RottaM. PissinateK. VillelaA.D. BackD.F. TimmersL.F.S.M. BachegaJ.F.R. de SouzaO.N. SantosD.S. BassoL.A. MachadoP. Piperazine derivatives: Synthesis, inhibition of the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase and SAR studies.Eur. J. Med. Chem.20159043644710.1016/j.ejmech.2014.11.034 25461892
     [Google Scholar]
  53. HeX. AlianA. Ortiz de MontellanoP.R. Inhibition of the Mycobacterium tuberculosis enoyl acyl carrier protein reductase InhA by arylamides.Bioorg. Med. Chem.200715216649665810.1016/j.bmc.2007.08.013 17723305
     [Google Scholar]
  54. KuoM.R. MorbidoniH.R. AllandD. SneddonS.F. GourlieB.B. StaveskiM.M. LeonardM. GregoryJ.S. JanjigianA.D. YeeC. MusserJ.M. KreiswirthB. IwamotoH. PerozzoR. JacobsW.R.Jr SacchettiniJ.C. FidockD.A. Targeting tuberculosis and malaria through inhibition of enoyl reductase: Compound activity and structural data.J. Biol. Chem.200327823208512085910.1074/jbc.M211968200 12606558
     [Google Scholar]
  55. FrijaL.M.T. PombeiroA.J.L. KopylovichM.N. Building 1,2,4‐Thiadiazole: Ten years of progress.Eur. J. Org. Chem.20172017192670268210.1002/ejoc.201601642
     [Google Scholar]
  56. CastroA. CastañoT. EncinasA. PorcalW. GilC. Advances in the synthesis and recent therapeutic applications of 1,2,4-thiadiazole heterocycles.Bioorg. Med. Chem.20061451644165210.1016/j.bmc.2005.10.012 16249092
     [Google Scholar]
  57. DawoodK.M. FarghalyT.A. Thiadiazole inhibitors: A patent review.Expert Opin. Ther. Pat.201727447750510.1080/13543776.2017.1272575
     [Google Scholar]
  58. DoğanH. DoğanŞ.D. GündüzM.G. KrishnaV.S. LherbetC. SriramD. ŞahinO. SarıpınarE. Discovery of hydrazone containing thiadiazoles as Mycobacterium tuberculosis growth and enoyl acyl carrier protein reductase (InhA) inhibitors.Eur. J. Med. Chem.202018811203510.1016/j.ejmech.2020.112035 31951850
     [Google Scholar]
  59. Ballell PagesL Castro PichelJ Fernandez MenendezR Fernandez VelandoEP Gonzalez del ValleS Leon DiazML Mendoza LosanaA WolfendaleMJ (Pyrazol-3-yl)-1,3,4-thiadiazole- 2-amine and (Pyrazol-3-yl)-1,3,4-thiazol-2-amine Compounds.W.O. Patent /2010/1188522010
  60. ShirudeP.S. MadhavapeddiP. NaikM. MuruganK. ShindeV. NandishaiahR. BhatJ. KumarA. HameedS. HoldgateG. DaviesG. McMikenH. HegdeN. AmbadyA. VenkatramanJ. PandaM. BandodkarB. SambandamurthyV.K. ReadJ.A. Methyl-thiazoles: a novel mode of inhibition with the potential to develop novel inhibitors targeting InhA in Mycobacterium tuberculosis.J. Med. Chem.201356218533854210.1021/jm4012033 24107081
     [Google Scholar]
  61. ŠinkR. SosičI. ŽivecM. Fernandez-MenendezR. TurkS. PajkS. Alvarez-GomezD. Lopez-RomanE.M. Gonzales-CortezC. Rullas-TriconadoJ. Angulo-BarturenI. BarrosD. Ballell-PagesL. YoungR.J. EncinasL. GobecS. Design, synthesis, and evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis.J. Med. Chem.201558261362410.1021/jm501029r 25517015
     [Google Scholar]
  62. KumarS. KhokraS.L. YadavA. Triazole analogues as potential pharmacological agents: A brief review.Future Journal of Pharmaceutical Sciences20217110610.1186/s43094‑021‑00241‑3 34056014
     [Google Scholar]
  63. YanM. XuL. WangY. WanJ. LiuT. LiuW. WanY. ZhangB. WangR. LiQ. Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents.Drug Dev. Res.202081440241810.1002/ddr.21638 31904877
     [Google Scholar]
  64. BozorovK. ZhaoJ. AisaH.A. 1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview.Bioorg. Med. Chem.201927163511353110.1016/j.bmc.2019.07.005 31300317
     [Google Scholar]
  65. KarczmarzykZ. Swatko-OssorM. WysockiW. DrozdM. GinalskaG. Pachuta-StecA. PituchaM. New application of 1,2,4-triazole derivatives as antitubercular agents. structure, in vitro screening and docking studies.Molecules20202524603310.3390/molecules25246033 33352814
     [Google Scholar]
  66. ZampieriD. CateniF. MoneghiniM. ZacchignaM. LauriniE. MarsonD. De LoguA. SannaA. MamoloM.G. Imidazole and 1,2,4-triazole-based derivatives gifted with antitubercular activity: cytotoxicity and computational assessment.Curr. Top. Med. Chem.201919862063210.2174/1568026619666190227183826 30827247
     [Google Scholar]
  67. El SawyM.A. ElshatanofyM.M. El KilanyY. KandeelK. ElwakilB.H. HagarM. AouadM.R. AlbelwiF.F. RezkiN. JaremkoM. El AshryE.S.H. Novel Hybrid 1,2,4- and 1,2,3-Triazoles targeting Mycobacterium tuberculosis enoyl acyl carrier protein reductase (InhA): Design, synthesis, and molecular docking.Int. J. Mol. Sci.2022239470610.3390/ijms23094706 35563096
     [Google Scholar]
  68. KunešJ. BažantJ. PourM. WaisserK. ŠlosárekM. JanotaJ. Quinazoline derivatives with antitubercular activity.Farmaco20005511-1272572910.1016/S0014‑827X(00)00100‑2 11204949
     [Google Scholar]
  69. WangW. ZouP.S. PangL. PanC.X. MoD.L. SuG.F. Recent advances in the synthesis of 2,3-fused quinazolinones.Org. Biomol. Chem.202220326293631310.1039/D2OB00778A 35838160
     [Google Scholar]
  70. KushwahaN. SahuA. MishraJ. SoniA. DorwalD. An insight on the prospect of quinazoline and quinazolinone derivatives as anti-tubercular agents.Curr. Org. Synth.202320883886910.2174/1570179420666230316094435 36927421
     [Google Scholar]
  71. AbuelizzH.A. Al-SalahiR. An overview of triazoloquinazolines: Pharmacological significance and recent developments.Bioorg. Chem.202111510526310.1016/j.bioorg.2021.105263 34426148
     [Google Scholar]
  72. PedgaonkarG.S. SrideviJ.P. JeankumarV.U. SaxenaS. DeviP.B. RenukaJ. YogeeswariP. SriramD. Development of 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives as novel enoyl-acyl carrier protein reductase (InhA) inhibitors for the treatment of tuberculosis.Eur. J. Med. Chem.20148661362710.1016/j.ejmech.2014.09.028 25218910
     [Google Scholar]
  73. PazJ.D. Denise de Moura SperottoN. RamosA.S. PissinateK. da Silva Rodrigues JuniorV. AbbadiB.L. BorsoiA.F. RamboR.S. Corso MinottoA.C. da Silva DaddaA. GalinaL. Macchi HopfF.S. MunizM.N. Borges MartinelliL.K. RothC.D. Madeira SilvaR.B. PerellóM.A. de Matos CzeczotA. NevesC.E. DuarteL.S. LeyserM. Dias de OliveiraS. BizarroC.V. MachadoP. BassoL.A. Novel 4-aminoquinolines: Synthesis, inhibition of the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase, antitubercular activity, SAR, and preclinical evaluation.Eur. J. Med. Chem.2023245Pt 111490810.1016/j.ejmech.2022.114908 36435016
     [Google Scholar]
  74. Gallardo-MaciasR. KumarP. JaskowskiM. RichmannT. ShresthaR. RussoR. SingletonE. ZimmermanM.D. HoH.P. DartoisV. ConnellN. AllandD. FreundlichJ.S. Optimization of N-benzyl-5-nitrofuran-2-carboxamide as an antitubercular agent.Bioorg. Med. Chem. Lett.201929460160610.1016/j.bmcl.2018.12.053 30600207
     [Google Scholar]
  75. VeeravarapuH. MalkhedV. MustyalaK.K. VadijaR. MalikantiR. VuruputuriU. MuthyalaM.K.K. Structure-based drug design, synthesis and screening of MmaA1 inhibitors as novel anti-TB agents.Mol. Divers.202125135136610.1007/s11030‑020‑10107‑0 32533514
     [Google Scholar]
  76. NimbalkarU.D. SeijasJ.A. BorkuteR. DamaleM.G. SangshettiJ.N. SarkarD. NikaljeA.P.G. Ultrasound assisted synthesis of 4-(benzyloxy)-n-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) benzamide as challenging anti-tubercular scaffold.Molecules2018238194510.3390/molecules23081945 30081525
     [Google Scholar]
  77. SrinivasaraoS. NandikollaA. SureshA. CalsterK.V. De VoogtL. CappoenD. GhoshB. AggarwalH. MurugesanS. Chandra SekharK.V.G. Seeking potent anti-tubercular agents: design and synthesis of substituted- N -(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents.RSC Advances20201021122721228810.1039/D0RA01348J 35497605
     [Google Scholar]
  78. NawrotD. SuchánkováE. JanďourekO. KonečnáK. BártaP. DoležalM. ZitkoJ. N ‐pyridinylbenzamides: an isosteric approach towards new antimycobacterial compounds.Chem. Biol. Drug Des.202197368670010.1111/cbdd.13804 33068457
     [Google Scholar]
  79. GuardiaA. GultenG. FernandezR. GómezJ. WangF. ConveryM. BlancoD. MartínezM. Pérez-HerránE. AlonsoM. OrtegaF. RullásJ. CalvoD. MataL. YoungR. SacchettiniJ.C. Mendoza-LosanaA. RemuiñánM. Ballell PagesL. Castro-PichelJ. N ‐Benzyl‐4‐((heteroaryl)methyl)benzamides: a new class of direct nadh‐dependent 2‐ trans enoyl–acyl carrier protein reductase (InhA) inhibitors with antitubercular activity.ChemMedChem201611768770110.1002/cmdc.201600020 26934341
     [Google Scholar]
  80. TrotskoN. Antitubercular properties of thiazolidin-4-ones – A review.Eur. J. Med. Chem.202121511326610.1016/j.ejmech.2021.113266 33588179
     [Google Scholar]
  81. AlegaonS.G. AlagawadiK.R. SonkusareP.V. ChaudharyS.M. DadweD.H. ShahA.S. Novel imidazo[2,1-b][1,3,4]thiadiazole carrying rhodanine-3-acetic acid as potential antitubercular agents.Bioorg. Med. Chem. Lett.20122251917192110.1016/j.bmcl.2012.01.052 22325950
     [Google Scholar]
  82. ChengS. ZouY. ChenX. ChenJ. WangB. TianJ. YeF. LuY. HuangH. LuY. ZhangD. Design, synthesis and biological evaluation of 3-substituted-2-thioxothiazolidin-4-one (rhodanine) derivatives as antitubercular agents against Mycobacterium tuberculosis protein tyrosine phosphatase B.Eur. J. Med. Chem.202325811557110.1016/j.ejmech.2023.115571 37348296
     [Google Scholar]
  83. XuJ.F. WangT.T. YuanQ. DuanY.T. XuY.J. LvP.C. WangX.M. YangY.S. ZhuH.L. Discovery and development of novel rhodanine derivatives targeting enoyl-acyl carrier protein reductase.Bioorg. Med. Chem.20192781509151610.1016/j.bmc.2019.02.043 30846404
     [Google Scholar]
  84. SlepikasL. ChirianoG. PerozzoR. TardyS. KranjcA. Patthey-VuadensO. Ouertatani-SakouhiH. KickaS. HarrisonC.F. ScrignariT. PerronK. HilbiH. SoldatiT. CossonP. TaraseviciusE. ScapozzaL. in silico driven design and synthesis of rhodanine derivatives as novel antibacterials targeting the enoyl reductase InhA.J. Med. Chem.20165924109171092810.1021/acs.jmedchem.5b01620 26730986
     [Google Scholar]
  85. ZervosenA. LuW.P. ChenZ. WhiteR.E. DemuthT.P.Jr FrèreJ.M. Interactions between penicillin-binding proteins (PBPs) and two novel classes of PBP inhibitors, arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones.Antimicrob. Agents Chemother.200448396196910.1128/AAC.48.3.961‑969.2004 14982790
     [Google Scholar]
  86. MarinerK.R. TrowbridgeR. AgarwalA.K. MillerK. O’NeillA.J. FishwickC.W.G. ChopraI. Furanyl-rhodanines are unattractive drug candidates for development as inhibitors of bacterial RNA polymerase.Antimicrob. Agents Chemother.201054104506450910.1128/AAC.00753‑10 20660693
     [Google Scholar]
  87. Villain-GuillotP. GualtieriM. BastideL. RoquetF. MartinezJ. AmblardM. PugniereM. LeonettiJ.P. Structure-activity relationships of phenyl-furanyl-rhodanines as inhibitors of RNA polymerase with antibacterial activity on biofilms.J. Med. Chem.200750174195420410.1021/jm0703183 17665895
     [Google Scholar]
  88. AndleebH. TehseenY. JabeenF. KhanI. IqbalJ. HameedS. Exploration of thioxothiazolidinone–sulfonate conjugates as a new class of aldehyde/aldose reductase inhibitors: A synthetic and computational investigation.Bioorg. Chem.20177511510.1016/j.bioorg.2017.08.009 28888096
     [Google Scholar]
  89. KumarG. ParasuramanP. SharmaS.K. BanerjeeT. KarmodiyaK. SuroliaN. SuroliaA. Discovery of a rhodanine class of compounds as inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase.J. Med. Chem.200750112665267510.1021/jm061257w 17477517
     [Google Scholar]
  90. YounisM.H. MohammedE.R. MohamedA.R. Abdel-AzizM.M. GeorgeyH.H. Abdel GawadN.M. Design, synthesis and anti-Mycobacterium tuberculosis evaluation of new thiazolidin-4-one and thiazolo[3,2-a][1,3,5]triazine derivatives.Bioorg. Chem.202212410580710.1016/j.bioorg.2022.105807 35487073
     [Google Scholar]
  91. PedgaonkarG.S. VariamJ.P. Ullas JeankumarVU Development of benzo[d]oxazol-2(3H)-ones derivatives as novel inhibitors of Mycobacterium tuberculosis InhA.Bioorg. Med. Chem.20142221613445
     [Google Scholar]
  92. PflégrV. HorváthL. StolaříkováJ. PálA. KordulákováJ. BőszeS. VinšováJ. KrátkýM. Design and synthesis of 2-(2-isonicotinoylhydrazineylidene)propanamides as InhA inhibitors with high antitubercular activity.Eur. J. Med. Chem.202122311366810.1016/j.ejmech.2021.113668 34198149
     [Google Scholar]
  93. SanjayS. GirishC. ToiP.C. BobbyZ. Gallic acid attenuates isoniazid and rifampicin-induced liver injury by improving hepatic redox homeostasis through influence on Nrf2 and NF-κB signalling cascades in Wistar rats.J. Pharm. Pharmacol.202173447348610.1093/jpp/rgaa048 33793834
     [Google Scholar]
  94. RehbergN. OmejeE. EbadaS.S. van GeelenL. LiuZ. SureechatchayanP. KassackM.U. IoergerT.R. ProkschP. KalscheuerR. 3- O -Methyl-Alkylgallates Inhibit Fatty Acid Desaturation in Mycobacterium tuberculosis.Antimicrob. Agents Chemother.2019639e001361910.1128/AAC.00136‑19 31209015
     [Google Scholar]
  95. ChinsembuK.C. Tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.Acta Trop.2016153465610.1016/j.actatropica.2015.10.004
     [Google Scholar]
  96. Hernández-GarcíaE. GarcíaA. Garza-GonzálezE. Avalos-AlanísF.G. Rivas-GalindoV.M. Rodríguez-RodríguezJ. Alcantar-RosalesV.M. Delgadillo-PugaC. del Rayo Camacho-CoronaM. Chemical composition of Acacia farnesiana (L) wild fruits and its activity against Mycobacterium tuberculosis and dysentery bacteria.J. Ethnopharmacol.2019230748010.1016/j.jep.2018.10.031 30367988
     [Google Scholar]
  97. SaharanV.D. MahajanS.S. Development of gallic acid formazans as novel enoyl acyl carrier protein reductase inhibitors for the treatment of tuberculosis.Bioorg. Med. Chem. Lett.201727480881510.1016/j.bmcl.2017.01.026 28117201
     [Google Scholar]
  98. RožmanK. SosičI. FernandezR. YoungR.J. MendozaA. GobecS. EncinasL. A new golden age for the antitubercular target InhA.Drug Discov. Today201722349250210.1016/j.drudis.2016.09.009 27663094
     [Google Scholar]
  99. Martínez-HoyosM. Perez-HerranE. GultenG. EncinasL. Álvarez-GómezD. AlvarezE. Ferrer-BazagaS. García-PérezA. OrtegaF. Angulo-BarturenI. Rullas-TrincadoJ. Blanco RuanoD. TorresP. CastañedaP. HussS. Fernández MenéndezR. González del ValleS. BallellL. BarrosD. ModhaS. DharN. Signorino-GeloF. McKinneyJ.D. García-BustosJ.F. LavanderaJ.L. SacchettiniJ.C. JimenezM.S. Martín-CasabonaN. Castro-PichelJ. Mendoza-LosanaA. Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor.EBioMedicine2016829130110.1016/j.ebiom.2016.05.006 27428438
     [Google Scholar]
  100. PhusiN. HashimotoY. OtsuboN. ImaiK. ThongdeeP. SukchitD. KamsriP. PunkvangA. SuttisintongK. PungpoP. KuritaN. Structure-based drug design of novel M. tuberculosis InhA inhibitors based on fragment molecular orbital calculations.Comput. Biol. Med.202315210643410.1016/j.compbiomed.2022.106434 36543008
     [Google Scholar]
  101. TenevaY. SimeonovaR. ValchevaV. AngelovaV.T. Recent advances in anti-tuberculosis drug discovery based on hydrazide-hydrazone and thiadiazole derivatives targeting InhA.Pharmaceuticals (Basel)202316448410.3390/ph16040484 37111241
     [Google Scholar]
  102. ShaabanM. MahranM. TelebM. RagabH. The key players in the arsenal of combating TB; Reviewing the lead InhA inhibitors.J. Adv. Pharmac. Sci.202400183310.21608/japs.2024.270897.1016
     [Google Scholar]
  103. MiJ. GongW. WuX. Advances in key drug target identification and new drug development for tuberculosis.BioMed Res. Int.2022202212310.1155/2022/5099312 35252448
     [Google Scholar]
/content/journals/mrmc/10.2174/0113895575309785240902102421
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Development of Mycobacterium tuberculosis Enoyl Acyl Reductase (InhA) Inhibitors: A Mini-Review
Mini Rev Med Chem 25, 219 (2025); https://doi.org/10.2174/0113895575309785240902102421
/content/journals/mrmc/10.2174/0113895575309785240902102421
/content/journals/mrmc/10.2174/0113895575309785240902102421
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  • Article Type:     Review Article
Keyword(s): antitubercular agents; enoyl acyl carrier protein reductase; first-line drug regimens; InhA inhibitors; Mycobacterium tuberculosis; tuberculosis

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