Skip to content
2000
Volume 32, Issue 33
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Introduction

This study involves several recently synthesized Schiff base derivatives of hydrochlorothiazide (), characterized by advanced spectroscopic techniques including Fourier transform infrared (FTIR), 1H-, 13C-NMR (Nuclear magnetic resonance), and High-resolution electrospray ionization mass spectrometry (HR-ESI-MS).

Methods

Hydrochlorothiazide (HCTZ, 2 mM) was mixed with 2 mM aldehydes in ethanol (20 mL) in the presence of glacial acetic acid, and the product was stirred with the help of a magnetic stirrer under the specified conditions. Keeping in mind the importance of imine derivatives against DPPH radical, the synthesized compounds were evaluated for antioxidant activity () using DPPH assay and diuretic activity () by Lipschitz method. All derivatives demonstrated notable antioxidant activity, exhibiting 52-86% inhibition.

Results

The compounds - also displayed remarkable diuretic effects in an model at a dose of 50 mg/kg. The computational studies of all the newly synthesized compounds were interpreted for the diuretic activity at the molecular level against human renal outer medullary potassium channel (ROMK1, PDB: ID) protein present on the nephron involved in diuresis indicating all compounds showed significant interactions at all receptors.

Conclusion

As the derivatives were more active than drugs in some regards; therefore, these derivatives will be beneficial and open new windows for research and additional pharmacological screening could be planned as part of the project's extension.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673328757241223034116
2025-01-31
2025-11-21

  • From This Site

    /content/journals/cmc/10.2174/0109298673328757241223034116
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. GuytonA.C. Text Book of Medical PhysiologyChina200611091
     [Google Scholar]
  2. DavidsonK. JonasB.S. DixonK.E. MarkovitzJ.H. Do depression symptoms predict early hypertension incidence in young adults in the CARDIA study? Coronary artery risk development in young adults.Arch. Intern. Med.2000160101495150010.1001/archinte.160.10.149510826464
     [Google Scholar]
  3. OngK.L. BarterP.J. WatersD.D. Cardiovascular drugs that increase the risk of new-onset diabetes.Am. Heart J.2014167442142810.1016/j.ahj.2013.12.02524655688
     [Google Scholar]
  4. SkaletzkyL.L. GrahamB.E. SzmuszkoviczJ. Relation between structure, stereochemistry, and diuretic activity in the 2-amino-.alpha.-phenylcyclohexanemethanol series, a new class of diuretic agents. II.J. Med. Chem.196912697798810.1021/jm00306a0045351478
     [Google Scholar]
  5. PerriconeS.C. HumphreyS.J. SkaletzkyL.L. GrahamB.E. ZandtR.A. ZinsG.R. Synthesis and diuretic activity of alkyl- and arylguanidine analogs of N,N′-dicyclohexyl-4-morpholinecarboxamidine in rats and dogs.J. Med. Chem.199437223693370010.1021/jm00048a0057966129
     [Google Scholar]
  6. MatthewsK.A. BrennerM.J. BrennerA.C. Evaluation of the efficacy and safety of a hydrochlorothiazide to chlorthalidone medication change in veterans with hypertension.Clin. Ther.20133591423143010.1016/j.clinthera.2013.07.43023993697
     [Google Scholar]
  7. MironneauJ. SavineauJ.P. MironneauC. Compared effects of indapamide, hydrochlorothiazide and chlorthalidone on electrical and mechanical activities in vascular smooth muscle.Eur. J. Pharmacol.1981752-310911310.1016/0014‑2999(81)90068‑67318900
     [Google Scholar]
  8. MichelleA. Lippincott’s Illustrated Reviews: Pharmacology5th edition2012612
     [Google Scholar]
  9. AbuamerK.M. MaihubA.A. El-AjailyM.M. EtorkiA.M. Abou-KrishaM.M. AlmaganiM.A. The role of aromatic schiff bases in the dyes techniques.Int. J. Org. Chem.2014471510.4236/ijoc.2014.41002
     [Google Scholar]
  10. a MounikaK. PragathiA. GyanakumariC. Synthesis characterization and biological activity of a Schiff base derived from 3-ethoxy salicylaldehyde and 2-amino benzoic acid and its transition metal complexes.J. Sci. Res.201023513
     [Google Scholar]
  11. (b KazamaC.C. Involvement of arginine-vasopressin in the diuretic and hypotensive effects of Pereskia grandifolia Haw.(Cactaceae).J. Ethnopharmacol.201214418693
     [Google Scholar]
  12. TurnerS.T. BoerwinkleE. O’ConnellJ.R. BaileyK.R. GongY. ChapmanA.B. McDonoughC.W. BeitelsheesA.L. SchwartzG.L. GumsJ.G. PadmanabhanS. HiltunenT.P. CitterioL. DonnerK.M. HednerT. LanzaniC. MelanderO. SaarelaJ. RipattiS. WahlstrandB. ManuntaP. KontulaK. DominiczakA.F. Cooper-DeHoffR.M. JohnsonJ.A. Genomic association analysis of common variants influencing antihypertensive response to hydrochlorothiazide.Hypertension201362239139710.1161/HYPERTENSIONAHA.111.0043623753411
     [Google Scholar]
  13. a) NajmS. NaureenH. SultanaK. AnwarF. KhanM.M. NadeemH. SaeedM. Schiff-based metal complexes of lamotrigine: Design, synthesis, characterization, and biological evaluation.ACS Omega20216117719773010.1021/acsomega.1c0002733778282
     [Google Scholar]
  14. b) AsbatA. SaleemF. NajmS. IqbalJ. SyedM.A. AhmadS. HanifS. AzeemM. Synthesis, characterization, computational, anticancer and anti-inflammatory studies of pregabalin esters and their complexes with heavy metals.J. Mol. Struct.2022126413323410.1016/j.molstruc.2022.133234
     [Google Scholar]
  15. c) AyazM. AlamA. Zainab AssadM. JavedA. IslamM.S. RafiqH. AliM. AhmadW. KhanA. LatifA. Al-HarrasiA. AhmadM. Biooriented synthesis of ibuprofen-clubbed novel bis-schiff base derivatives as potential hits for malignant glioma: In vitro anticancer activity and in silico approach.ACS Omega2023851492284924310.1021/acsomega.3c0721638173864
     [Google Scholar]
  16. d) RafiqK. KhanM. MuhammedN. KhanA. Ur RehmanN. Al-YahyaeiB.E.M. KhiatM. HalimS.A. ShahZ. CsukR. Al-HarrasiA. New amino acid clubbed Schiff bases inhibit carbonic anhydrase II, α-glucosidase, and urease enzymes: In silico and in vitro.Med. Chem. Res.202130371272810.1007/s00044‑020‑02696‑0
     [Google Scholar]
  17. e) IsmailM. AhmadR. LatifA. KhanA.A. AhmadM. KhanA. Al-HarrasiA. AliM. An efficient synthesis of bis-Schiff’s bases of polyhydroquinoline derivatives via multistep reactions, anti-bacterial activities and DFT approach.J. Mol. Struct.2023129213605910.1016/j.molstruc.2023.136059
     [Google Scholar]
  18. f) KaushikS. PaliwalS.K. IyerM.R. PatilV.M. Promising Schiff bases in antiviral drug design and discovery.Med. Chem. Res.20233261063107610.1007/s00044‑023‑03068‑037305208
     [Google Scholar]
  19. YambeM. TomiyamaH. YamadaJ. KojiY. MotobeK. ShiinaK. YamamotoY. YamashinaA. Arterial stiffness and progression to hypertension in Japanese male subjects with high normal blood pressure.J. Hypertens.2007251879310.1097/01.hjh.0000254375.73241.e217143178
     [Google Scholar]
  20. Olde EngberinkR.H.G. FrenkelW.J. van den BogaardB. BrewsterL.M. VogtL. van den BornB.J.H. Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis.Hypertension20156551033104010.1161/HYPERTENSIONAHA.114.0512225733241
     [Google Scholar]
  21. NguyenN.H. SarangiS. McChesneyE.M. ShengS. PorterA.W. KleymanT.R. PitlukZ.W. BrodskyJ.L. Genome mining yields new disease-associated ROMK variants with distinct defects.bioRxiv2023202353960910.1101/2023.05.05.539609
     [Google Scholar]
  22. XavierA. SrividhyaN. Synthesis and study of Schiff base ligands.IOSR J. Appl. Chem.2014711615
     [Google Scholar]
  23. SahuR. ThakurD.S. PK. Schiff base: An overview of its medicinal chemistry potential for new drug molecules.IJPSN1970531757176410.37285/ijpsn.2012.5.3.2
     [Google Scholar]
  24. SwapnaM. BasavarajaH. JayadevaiahK. KumariN.D. BharathiD. Synthesis, charecterization and biological activities of some novel thiadiazole derivatives.JPSR201911621132120
     [Google Scholar]
  25. a) Al-OtaibiJ.S. MaryY.S. MaryY.S. ThomasR. Quantum mechanical and photovoltaic studies on the cocrystals of hydrochlorothiazide with isonazid and malonamide.J. Mol. Struct.2019119771972610.1016/j.molstruc.2019.07.110
     [Google Scholar]
  26. b) Abd El-halimH.F. OmarM.M. MohamedG.G. Synthesis, structural, thermal studies and biological activity of a tridentate Schiff base ligand and their transition metal complexes.Spectrochim. Acta A Mol. Biomol. Spectrosc.2011781364410.1016/j.saa.2010.06.00321130026
     [Google Scholar]
  27. AdãoJ.R.U. de SouzaP. BoeingT. MarianoL.N.B. BrandtA.M.F. HemmerJ.V. BazaniH.A.G. de AndradeS.F. CorrêaR. Klein-JúniorL.C. NieroR. Synthesis and characterization of Schiff base derivatives and its effect on urinary parameters of Wistar rats: A comparative analysis with different classes of diuretics.J. Mol. Struct.2022126013284910.1016/j.molstruc.2022.132849
     [Google Scholar]
  28. JabeenM. AhmadS. ShahidK. SadiqA. RashidU. Ursolic acid hydrazide based organometallic complexes: synthesis, characterization, antibacterial, antioxidant, and docking studies.Front Chem.201865510.3389/fchem.2018.0005529594100
     [Google Scholar]
  29. HuongD.Q. BayM.V. NamP.C. Antioxidant activity of thiourea derivatives: An experimental and theoretical study.J. Mol. Liq.202134011714910.1016/j.molliq.2021.117149
     [Google Scholar]
  30. WeberV. CoudertP. RubatC. DurouxE. LealF. CouqueletJ. Antioxidant properties of novel lipophilic ascorbic acid analogues.J. Pharm. Pharmacol.200052552353010.1211/002235700177431810864140
     [Google Scholar]
  31. DanglesO. FargeixG. DufourC. Antioxidant properties of anthocyanins and tannins: a mechanistic investigation with catechin and the 3′,4′,7-trihydroxyflavylium ion.J. Chem. Soc., Perkin Trans. 2200081653166310.1039/b003260n
     [Google Scholar]
  32. CeronC.S. CastroM.M. RizziE. MontenegroM.F. FontanaV. SalgadoM.C.O. GerlachR.F. Tanus-SantosJ.E. Spironolactone and hydrochlorothiazide exert antioxidant effects and reduce vascular matrix metalloproteinase-2 activity and expression in a model of renovascular hypertension.Br. J. Pharmacol.20101601778710.1111/j.1476‑5381.2010.00678.x20331602
     [Google Scholar]
  33. AntolovichM. PrenzlerP.D. PatsalidesE. McDonaldS. RobardsK. Methods for testing antioxidant activity.Analyst (Lond.)2002127118319810.1039/b009171p11827390
     [Google Scholar]
  34. AmuthanA. ChogtuB. BairyK.L. Sudhakar PrakashM. Evaluation of diuretic activity of Amaranthus spinosus Linn. aqueous extract in Wistar rats.J. Ethnopharmacol.2012140242442710.1016/j.jep.2012.01.04922331031
     [Google Scholar]
  35. HusainA. MadhesiaD. RashidM. AhmadA. KhanS.A. Synthesis and in vivo diuretic activity of some new benzothiazole sulfonamides containing quinoxaline ring system.J. Enzyme Inhib. Med. Chem.20163161682168910.3109/14756366.2015.112842526739592
     [Google Scholar]
  36. BhadoriyaU. TiwariS. SharmaP. BankeyS. MouryaM. Diuretic activity of extract of Salvia officinalis L.Asian J. Pharm. Life Sci2011112428
     [Google Scholar]
  37. LiuZ. YangL. LiL. WeiR. LuoX. XuT. HuangY. MuZ. HeJ. Diuretic and antidiuretic activities of ethanol extract and fractions of Lagopsis supina in normal rats.Biomed Res Int.20192019692737410.1155/2019/6927374
     [Google Scholar]
  38. MendesC. ButtchevitzA. KrugerJ.H. CaonT. de Oliveira BenedetP. Lemos-SennaE. SilvaM.A.S. Self- nanoemulsified drug delivery system of hydrochlorothiazide for increasing dissolution rate and diuretic activity.AAPS PharmSciTech20171872494250410.1208/s12249‑017‑0735‑z28213844
     [Google Scholar]
  39. a) ParishH.A.Jr GilliomR.D. PurcellW.P. BrowneR.K. SpirkR.F. WhiteH.D. Syntheses and diuretic activity of 1,2-dihydro-2-(3-pyridyl)-3H-pyrido[2,3-d]pyrimidin-4-one and related compounds.J. Med. Chem.19822519810210.1021/jm00343a0227086830
     [Google Scholar]
  40. b) GoldB. MirvishS.S. N-Nitroso derivatives of hydrochlorothiazide, niridazole, and tolbutamide.Toxicol. Appl. Pharmacol.197740113113610.1016/0041‑008X(77)90124‑7867427
     [Google Scholar]
  41. NaikV.R. AgshikarN.V. AbrahamG.J.S. Cucumis trigonus roxb. II. Diuretic activity.J. Ethnopharmacol.198131151910.1016/0378‑8741(81)90011‑87464192
     [Google Scholar]
  42. MahmoudW.H. DeghadiR.G. MohamedG.G. Metal complexes of ferrocenyl-substituted Schiff base: Preparation, characterization, molecular structure, molecular docking studies, and biological investigation.J. Organomet. Chem.202091712111310.1016/j.jorganchem.2020.121113
     [Google Scholar]
  43. BalaeiF. GhobadiS. Hydrochlorothiazide binding to human serum albumin induces some compactness in the molecular structure of the protein: A multi-spectroscopic and computational study.J. Pharm. Biomed. Anal.20191621810.1016/j.jpba.2018.09.00930218717
     [Google Scholar]
  44. AttiqueS.A. HassanM. UsmanM. AtifR.M. MahboobS. Al-GhanimK.A. BilalM. NawazM.Z. A molecular docking approach to evaluate the pharmacological properties of natural and synthetic treatment candidates for use against hypertension.Int. J. Environ. Res. Public Health201916692310.3390/ijerph1606092330875817
     [Google Scholar]
  45. ShahR. KatouahH. SedayoA.A. AbualnajaM. AljohaniM.M. SaadF. ZakyR. El-MetwalyN.M. Practical and computational studies on novel Schiff base complexes derived from green synthesis approach: Conductometry as well as in vitro screening supported by in silico study.J. Mol. Liq.202031911411610.1016/j.molliq.2020.114116
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673328757241223034116
Loading
Imine Derivatives of Hydrochlorothiazide Bear Potential Diuretic Activity in in vivo Experimental Model by Targeting Renal Outer Medullary Potassium Channel
Curr. Med. Chem. 32, 7434 (2025); https://doi.org/10.2174/0109298673328757241223034116
/content/journals/cmc/10.2174/0109298673328757241223034116
/content/journals/cmc/10.2174/0109298673328757241223034116
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): computational studies; diuretic activity; DPPH assay; Hydrochlorothiazide; hypertension; renal outer medullary potassium channel

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