Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Letters in Drug Design & Discovery
  4. Volume 21, Issue 18
  5. Article
Volume 21, Issue 18
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Tuberculosis (TB) remains a significant global health concern, necessitating the exploration of novel therapeutic agents. Reported antitubercular activities of previously synthesized benzopyran and other oxygen-containing heterocycles motivate us to synthesize and evaluate the antitubercular potential of benzopyran derivatives.

Objective

The aim of this study was to combine two scaffolds; one is coumarin (benzopyran-2-one), and another one is piperazine, as both are found in anti-tubercular derivatives.

Methods

Through a four-step synthetic approach, compounds SM1-SM10 were synthesized. These derivatives were subsequently evaluated for their anti-tubercular potential using the resazurin microtiter assay (REMA), with isoniazid as the standard (MIC 0.25 to 0.5µg/mL).

Results

Among the synthesized compounds, SM2 and SM8 demonstrated remarkable anti-tubercular activity, with MICs of 4 and 6µg/mL, respectively. Notably, these MIC values are considerable for the further development of benzopyran derivatives as potent antitubercular agents.

Conclusion

Outcomes underscore the potential of benzopyran derivatives as valuable assets in TB drug discovery, warranting further exploration and development.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/lddd/10.2174/0115701808332606241017075155
2024-11-04
2025-05-29

  • From This Site

    /content/journals/lddd/10.2174/0115701808332606241017075155
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BhargavaA. BhargavaM. Tuberculosis deaths are predictable and preventable: Comprehensive assessment and clinical care is the key.J. Clin. Tuberc. Other Mycobact. Dis.20201910015510.1016/j.jctube.2020.10015532211519
     [Google Scholar]
  2. DhamnetiyaD. PatelP. JhaR.P. ShriN. SinghM. BhattacharyyaK. Trends in incidence and mortality of tuberculosis in India over past three decades: A joinpoint and age–period–cohort analysis.BMC Pulm. Med.202121137510.1186/s12890‑021‑01740‑y34784911
     [Google Scholar]
  3. WHO. Global Tuberculosis Control a Short Update to the 2019 Report, World Health Organization, Geneva 2019. Available from: https://www.who.int/tb/publications/global_report/en/
  4. BussiC. GutierrezM.G. Mycobacterium tuberculosis infection of host cells in space and time.FEMS Microbiol. Rev.201943434136110.1093/femsre/fuz00630916769
     [Google Scholar]
  5. SmithI. Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence.Clin. Microbiol. Rev.200316346349610.1128/CMR.16.3.463‑496.200312857778
     [Google Scholar]
  6. PanteixG. GutierrezM.C. BoschiroliM.L. RouviereM. PlaidyA. PressacD. PorcheretH. ChyderiotisG. PonsadaM. OortegemV.K. SalloumS. CabuzelS. BañulsA.L. PerreV.D.P. GodreuilS. Pulmonary tuberculosis due to Mycobacterium microti: A study of six recent cases in France.J. Med. Microbiol.201059898498910.1099/jmm.0.019372‑020488936
     [Google Scholar]
  7. MarfilM.J. BlancoF.C. OlivieriC.M.A. EirinM.E. ZumárragaM.J. Transmissibility of Mycobacterium pinnipedii in a murine model.Front. Cell. Infect. Microbiol.202414132898110.3389/fcimb.2024.132898138606297
     [Google Scholar]
  8. RoeW.D. LentingB. KokosinskaA. HunterS. DuignanP.J. GartrellB. RogersL. CollinsD.M. LisleD.G.W. GedyeK. CarterP.M. Pathology and molecular epidemiology of Mycobacterium pinnipedii tuberculosis in native New Zealand marine mammals.PLoS One2019142e021236310.1371/journal.pone.021236330753243
     [Google Scholar]
  9. GonzalezT.P. HernandezC.M.E. GamboaM.A. GarciaG.L. HervertC.L.P. ValleB.D.M. LeonP.D.A. OsornioS.J. Human tuberculosis caused by mycobacterium bovis: A retrospective comparison with mycobacterium tuberculosis in a mexican tertiary care centre, 2000–2015.BMC Infect. Dis.201616165710.1186/s12879‑016‑2001‑527825312
     [Google Scholar]
  10. BéguecA.C. DufauxF.M. StoffelsK. OmmeslagD. WalravensK. SaegermanC. SupplyP. Importance of identifying Mycobacterium bovis as a causative agent of human tuberculosis.Eur. Respir. J.201035369269410.1183/09031936.0013730920190335
     [Google Scholar]
  11. LirolaM.M. HerranzM. SerranoB.S. GrandeR.C. InarraD.E. CárdenasG.J.A. RuizC.A.M. BermúdezM.P. RíoC.D.M. GalánG.V. ArmenterosL.J. MartínezV.J.M. GodoyV.S. GarcíaE.A.B. FernándezC.M.T. MuñozP. LagoP.L. ViedmaG.D.D. A One Health approach revealed the long-term role of Mycobacterium caprae as the hidden cause of human tuberculosis in a region of Spain, 2003 to 2022. Euro surveillance: Bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin202328122200852
     [Google Scholar]
  12. ValP.D.B. PereaC. EstruchJ. ManriqueS.C. RieraC. SanzA. VidalE. VelardeR. Generalized tuberculosis due to Mycobacterium caprae in a red fox phylogenetically related to livestock breakdowns.BMC Vet. Res.202218135210.1186/s12917‑022‑03454‑736127697
     [Google Scholar]
  13. SharmaA. BlossE. HeiligC.M. ClickE.S. Tuberculosis caused by Mycobacterium africanum, United States, 2004–2013.Emerg. Infect. Dis.201622339640310.3201/eid2203.15150526886258
     [Google Scholar]
  14. SabinS. ArceM.A.Y. PfeiferS.P. JensenJ.D. The impact of frequently neglected model violations on bacterial recombination rate estimation: A case study in Mycobacterium canettii and Mycobacterium tuberculosis.G32022125jkac05510.1093/g3journal/jkac05535253851
     [Google Scholar]
  15. ConnollyL.E. EdelsteinP.H. RamakrishnanL. Why is long-term therapy required to cure tuberculosis?PLoS Med.200743e12010.1371/journal.pmed.004012017388672
     [Google Scholar]
  16. PaddaI.S. ReddyM.K. Antitubercular medications.StatPearls.Treasure Island, FLStatPearls Publishing2024 https://www.ncbi.nlm.nih.gov/books/NBK557666/
    [Google Scholar]
  17. AlcaideF. SantínM. Multidrug-resistant tuberculosis.Enferm. Infecc. Micro. Boil. Clin.2008265460
     [Google Scholar]
  18. VerschoorJ.A. SikoD.G.R. WyngaardtS.V. Method for detecting mycobacterial infection. US0111125 A12009
     [Google Scholar]
  19. BeaS. LeeH. KimJ.H. JangS.H. SonH. KwonJ.W. ShinJ.Y. Adherence and associated factors of treatment regimen in drug-susceptible tuberculosis patients.Front. Pharmacol.20211262507810.3389/fphar.2021.62507833790788
     [Google Scholar]
  20. SharmaS.K. MohanA. Multidrug-resistant tuberculosis.Indian J. Med. Res.2004120435437615520486
     [Google Scholar]
  21. JangJ.G. ChungJ.H. Diagnosis and treatment of multidrug-resistant tuberculosis.Yeungnam Univ. J. Med.202037427728510.12701/yujm.2020.0062632883054
     [Google Scholar]
  22. ShinS.S. KeshavjeeS. GelmanovaI.Y. AtwoodS. FrankeM.F. MishustinS.P. StrelisA.K. AndreevY.G. PasechnikovA.D. BarnashovA. TonkelT.P. CohenT. Development of extensively drug-resistant tuberculosis during multidrug-resistant tuberculosis treatment.Am. J. Respir. Crit. Care Med.2010182342643210.1164/rccm.200911‑1768OC20413630
     [Google Scholar]
  23. SeungK.J. KeshavjeeS. RichM.L. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis.Cold Spring Harb. Perspect. Med.201559a01786310.1101/cshperspect.a01786325918181
     [Google Scholar]
  24. GiehlC. RoyR.B. KnellwolfA.L. The situation of HIV/M. tuberculosis co-infection in Europe.Open Infect. Dis. J.201152135
     [Google Scholar]
  25. MaseS.R. ChorbaT. Treatment of drug-resistant tuberculosis.Clin. Chest Med.201940477579510.1016/j.ccm.2019.08.00231731984
     [Google Scholar]
  26. KochA. CoxH. MizrahiV. Drug-resistant tuberculosis: Challenges and opportunities for diagnosis and treatment.Curr. Opin. Pharmacol.20184271510.1016/j.coph.2018.05.01329885623
     [Google Scholar]
  27. PradiptaI.S. IdrusL.R. ProbandariA. LestariB.W. DiantiniA. AlffenaarJ.W.C. HakE. Barriers and strategies to successful tuberculosis treatment in a high-burden tuberculosis setting: A qualitative study from the patient’s perspective.BMC Public Health2021211190310.1186/s12889‑021‑12005‑y34670527
     [Google Scholar]
  28. AnandN. SinghP. SharmaA. TiwariS. SinghV. SinghD.K. SrivastavaK.K. SinghB.N. TripathiR.P. Synthesis and evaluation of small libraries of triazolylmethoxy chalcones, flavanones and 2-aminopyrimidines as inhibitors of mycobacterial FAS-II and PknG.Bioorg. Med. Chem.201220175150516310.1016/j.bmc.2012.07.00922854194
     [Google Scholar]
  29. SandileB.S. PasekaT.M. RabanW.M. Benzopyran-core as an antimycobacterial agent.Organ. Med. Chem. Int. J.2020102567210.19080/OMCIJ.2020.10.555784
     [Google Scholar]
  30. ReddyD.S. KongotM. KumarA. Coumarin hybrid derivatives as promising leads to treat tuberculosis: Recent developments and critical aspects of structural design to exhibit anti-tubercular activity.Tuberculosis202112710205010.1016/j.tube.2020.10205033540334
     [Google Scholar]
  31. FengL. MaddoxM.M. AlamM.Z. TsutsumiL.S. NarulaG. BruhnD.F. WuX. SandhausS. LeeR.B. SimmonsC.J. DinhT.Y.C. HurdleJ.G. LeeR.E. SunD. Synthesis, structure-activity relationship studies, and antibacterial evaluation of 4-chromanones and chalcones, as well as olympicin A and derivatives.J. Med. Chem.201457208398842010.1021/jm500853v25238443
     [Google Scholar]
  32. BhuvaN.H. TalparaP.K. SingalaP.M. GothaliyaV.K. ShahV.H. Synthesis and biological evaluation of pyrimidinyl sulphonamide derivatives as promising class of antitubercular agents.J. Saudi Chem. Soc.2017215517527
     [Google Scholar]
  33. MaliH.M. SabaleS.S. DeganiM.S. BorkuteR. ChoudhariA.S. SarkarD. KrishnaV.S. SriramD. Rational design of coumarin derivatives as antituberculosis agents.Future Med. Chem.201810202431244410.4155/fmc‑2018‑001530325198
     [Google Scholar]
  34. AouamK. ChaabaneA. LoussaïefC. RomdhaneB.F. BoughattasN.A. ChakrounM. Adverse effects of anti-tuberculosis drugs: Epidemiology, mechanisms and actions to take.Med. Mal. Infect.200737525326110.1016/j.medmal.2006.12.00617336011
     [Google Scholar]
  35. PatilK. BagadeS. BondeS. SharmaS. SaraogiG. Recent therapeutic approaches for the management of tuberculosis: Challenges and opportunities.Biomed. Pharmacother.20189973574510.1016/j.biopha.2018.01.11529710471
     [Google Scholar]
  36. AbyshevA.Z. GindinV.A. SemenovE.V. AgaevE.M. ZadeA.A.A. GuseinovA.B. Structure and biological properties of 2H-1-benzopyran-2-one (coumarin) derivatives.Pharm. Chem. J.2006401160761010.1007/s11094‑006‑0203‑7
     [Google Scholar]
  37. KubackaM. MogilskiS. FilipekB. MaronaH. Antiarrhythmic properties of some 1,4-disubstituted piperazine derivatives with α1-adrenoceptor affinities.Eur. J. Pharmacol.20137201-323724610.1016/j.ejphar.2013.10.02124161912
     [Google Scholar]
  38. GuptaS. ParkS.E. MozaffariS. AaragE.B. ParangK. TiwariR.K. Design, synthesis, and antiproliferative activity of benzopyran-4-one-isoxazole hybrid compounds.Molecules20232810422010.3390/molecules2810422037241960
     [Google Scholar]
  39. OhtakaH. YoshidaK. SuzukiK. ShimoharaK. TajimaS. ItoK. Benzylpiperazine derivatives. VIII. Syntheses, antiulcer and cytoprotective activities of 1-(aminocarbonylalkyl)-4-benzylpiperazine derivatives and related compounds.Chem. Pharm. Bull.198836103948395410.1248/cpb.36.39483245974
     [Google Scholar]
  40. DingC.Z. AtwalK.S. Patent and Trademark Office. U.S. 5,869,4781999
     [Google Scholar]
  41. SollR.M. DollingsP.J. McCaullyR.J. ArgentieriT.M. LodgeN. OshiroG. ColatskyT. NortonN.W. ZebickD. HavensC. HalakaN. N-sulfonamides of benzopyran-related potassium channel openers: Conversion of glyburide insensitive smooth muscle relaxants to potent smooth muscle contractors.Bioorg. Med. Chem. Lett.19944576977310.1016/S0960‑894X(01)80198‑0
     [Google Scholar]
  42. SahooR.C. SahooJ. MahapatraM. LenkaD. SahuK.P. DehuryB. PadhyN.R. PaidesettyK.S. Coumarin derivatives as promising antibacterial agent(s).Arab. J. Chem.202114210292210.1016/j.arabjc.2020.102922
     [Google Scholar]
  43. ChandranM. RenukaJ. SrideviJ.P. PedgaonkarG.S. AsmithaV. YogeeswariP. SriramD. Benzothiazinone-piperazine derivatives as efficient Mycobacterium tuberculosis DNA gyrase inhibitors.Int. J. Mycobacteriol.20154210411510.1016/j.ijmyco.2015.02.00226972878
     [Google Scholar]
  44. PalominoJ.C. MartinA. CamachoM. GuerraH. SwingsJ. PortaelsF. Resazurin microtiter assay plate: Simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis.Antimicrob. Agents Chemother.20024682720272210.1128/AAC.46.8.2720‑2722.200212121966
     [Google Scholar]
  45. KhalifaR.A. NasserM.S. GomaaA.A. OsmanN.M. SalemH.M. Resazurin microtiter assay plate method for detection of susceptibility of multidrug resistant Mycobacterium tuberculosis to second-line anti-tuberculous drugs.Egypt. J. Chest Dis. Tuberc.201362224124710.1016/j.ejcdt.2013.05.008
     [Google Scholar]
  46. DattaP. MukhopadhyayA.P. MannaP. TiekinkE.R.T. SilP.C. SinhaC. Structure, photophysics, electrochemistry, DFT calculation, and in-vitro antioxidant activity of coumarin Schiff base complexes of Group 6 metal carbonyls.J. Inorg. Biochem.2011105457758810.1016/j.jinorgbio.2010.04.01321419093
     [Google Scholar]
  47. GuhaS. LoharS. BolteM. SafinD.A. DasD. Crystal structure and interaction of 6-amino coumarin with nitrite ion for its selective fluorescence detection.Spectrosc. Lett.201245322523510.1080/00387010.2011.605416
     [Google Scholar]
  48. MohammedA.Y. AhamedL.S. Synthesis and characterization of new substituted coumarin derivatives and study their biological activity.Chem. Methodol20226813822
     [Google Scholar]
  49. MorganG.T. MicklethwaitF.M.G. CXXV.—6-Aminocoumarin.J. Chem. Soc. Trans.19048501230123810.1039/CT9048501230
     [Google Scholar]
  50. AminK.M. TahaA.M. GeorgeR.F. MohamedN.M. ElsendunyF.F. Synthesis, antitumor activity evaluation, and DNA‐binding study of coumarin‐based agents.Arch. Pharm.20183511170019910.1002/ardp.20170019929148081
     [Google Scholar]
  51. KumarD. SharmaP. LobeM.M. KaurS. SinghT.G. DuaK. KangN.F. Emerging oxygen based heterocyclic scaffolds as potential anticancer candidates.Preprints2023202308106410.20944/preprints202308.1064.v1
     [Google Scholar]
  52. VenkatachalamH. KumarN.V. The oxygen-containing fused heterocyclic compounds.In: Heterocycles - Synthesis and Biological Activities; IntechOpen2019113
     [Google Scholar]
  53. SongL. MerceronR. GraciaB. QuintanaA.L. RisseeuwM.D.P. HulpiaF. CosP. AínsaJ.A. LehmannM.H. SavvidesS.N. CalenberghV.S. Structure guided lead generation toward nonchiral M. tuberculosis thymidylate kinase inhibitors.J. Med. Chem.20186172753277510.1021/acs.jmedchem.7b0157029510037
     [Google Scholar]
  54. SongL. MerceronR. HulpiaF. LucíaA. GraciaB. JianY. RisseeuwM.D.P. VerstraelenT. CosP. AínsaJ.A. BoshoffH.I. LehmannM.H. SavvidesS.N. CalenberghV.S. Structure-aided optimization of non-nucleoside M. tuberculosis thymidylate kinase inhibitors.Eur. J. Med. Chem.202122511378410.1016/j.ejmech.2021.11378434450493
     [Google Scholar]
  55. KhanM.K.A. KrishmanA. KhanM.K.A. Protein kinases as antituberculosis targets The case of thymidylate kinases.Front. Biosci.20202591636165410.2741/487132114448
     [Google Scholar]
  56. XieZ. YangX. DuanY. HanJ. LiaoC. Small-molecule kinase inhibitors for the treatment of nononcologic diseases.J. Med. Chem.20216431283134510.1021/acs.jmedchem.0c0151133481605
     [Google Scholar]
  57. CuiQ. ShinW.S. LuoY. TianJ. CuiH. YinD. Thymidylate kinase: An old topic brings new perspectives.Curr. Med. Chem.201320101286130510.2174/092986731132010000623394555
     [Google Scholar]
  58. SammartinoJ.C. MoriciM. StelitanoG. DegiacomiG. RiccardiG. ChiarelliL.R. Functional investigation of the antitubercular drug target Decaprenylphosphoryl-β-D-ribofuranose-2-epimerase DprE1/DprE2 complex.Biochem. Biophys. Res. Commun.2022607495310.1016/j.bbrc.2022.03.09135366543
     [Google Scholar]
/content/journals/lddd/10.2174/0115701808332606241017075155
Loading
Exploring Novel Benzopyran Derivatives as Antitubercular Agents
Letters in Drug Design & Discovery 21, 4321 (2024); https://doi.org/10.2174/0115701808332606241017075155
/content/journals/lddd/10.2174/0115701808332606241017075155
/content/journals/lddd/10.2174/0115701808332606241017075155
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Antitubercular; benzopyran; mycobacterium thymidine monophosphate kinase (Mtb TMPK); pharmacophore; piperazine; resazurin microtiter assay (REMA)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test