Skip to content
2000
Volume 21, Issue 5
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Introduction

In the present work, a series of novel pyridine carboxamides were synthesized and screened with antibacterial activity. This research explores the application of Density Functional Theory (DFT) in studying biological systems at the quantum mechanical level, particularly in the context of drug design. DFT offers a streamlined approach to quantum mechanical calculations, making it indispensable in various scientific fields, and for its exceptional accuracy, reduced computational time, and cost-effectiveness has become a pivotal tool in computational chemistry. This research work highlights the integration of DFT studies with POM analyses, which effectively identify pharmacophoric sites. Moreover, the research incorporates pharmacokinetics analyses to assess the pharmacokinetic properties of synthesized compounds. The paper focused on a series of compounds previously reported, aiming to provide a comprehensive understanding of their electronic structure, pharmacophoric features, and potential as drug candidates. This study not only contributes to the evolving field of computational chemistry but also holds implications for advancing drug design processes by combining theoretical insights with practical analyses.

Methods

The compounds were subjected to Density Functional Theory (DFT) computations using the B3LYP/6-31G(d) basis set to get optimized geometric structures. GaussViewis used to display the contributions of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). The determination of energy gaps was conducted using Gaussian 09W. The pharmacokinetic profiles were evaluated using existing techniques such as Osiris, Petra, and Molinspiration, as well as a novel platform called POM Analyse.

Results

The computational studies DFT, POM and pharmacokinetics studies revealed that the studied compounds are biologically active, non-toxic, non-carcinogenic in nature and may be utilized as drug candidates.

Conclusion

Density functional theory (DFT) investigations emphasize the exceptional stability of complex , which possesses the biggest energy gap and the lowest softness. In contrast, compound demonstrates poorer stability among the tested compounds, characterized by the lowest energy gap and the highest softness values. These findings are further substantiated by absolute energy calculations. The negligible energy difference in compound indicates an increased transfer of electric charge within the molecule, which is associated with its enhanced biological effectiveness. The drug-likeness of the compounds is confirmed by POM and pharmacokinetics investigations, with compound being identified as the most biologically active among the investigated compounds.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/mc/10.2174/0115734064293464240405050455
2024-04-17
2025-09-11

  • From This Site

    /content/journals/mc/10.2174/0115734064293464240405050455
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. XingJ. WangC. AnthonyE.J. An overview for DFT application on arsenic behavior in coal-fired power plants.Fuel202335312912910.1016/j.fuel.2023.129129
     [Google Scholar]
  2. SpergerT. SanhuezaI.A. KalvetI. SchoenebeckF. Computational studies of synthetically relevant homogeneous organometallic catalysis involving Ni, Pd, Ir, and Rh: An overview of commonly employed DFT methods and mechanistic insights.Chem. Rev.2015115179532958610.1021/acs.chemrev.5b00163 26207572
     [Google Scholar]
  3. MakhloufJ. LouisH. BenjaminI. UkwenyaE. ValkonenA. SmiraniW. Single crystal investigations, spectral analysis, DFT studies, antioxidants, and molecular docking investigations of novel hexaisothiocyanato chromate complex.J. Mol. Struct.2023127213422310.1016/j.molstruc.2022.134223
     [Google Scholar]
  4. ObotI.B. MacdonaldD.D. GasemZ.M. Density functional theory (DFT) as a powerful tool for designing new organic corrosion inhibitors. Part 1: An overview.Corros. Sci.20159913010.1016/j.corsci.2015.01.037
     [Google Scholar]
  5. SharmaA.K. NishadG.R. VishwakarmaP.K. JagetP.S. Density functional theory (dft)-based molecular modeling. In: Computational modelling and simulations for designing of corrosion inhibitors.Elsevier202311513310.1016/B978‑0‑323‑95161‑6.00001‑1
     [Google Scholar]
  6. BasedenK.A. TyeJ.W. Introduction to density functional theory: Calculations by hand on the helium atom.J. Chem. Educ.201491122116212310.1021/ed5004788
     [Google Scholar]
  7. HaunschildR. BarthA. MarxW. Evolution of DFT studies in view of a scientometric perspective.J. Cheminform.2016815210.1186/s13321‑016‑0166‑y 28316650
     [Google Scholar]
  8. BurschM. MewesJ.M. HansenA. GrimmeS. Best‐practice dft protocols for basic molecular computational chemistry.Angew. Chem. Int. Ed.20226142e20220573510.1002/anie.202205735 36103607
     [Google Scholar]
  9. HefnawyM.A. FadlallahS.A. SherifE.R.M. MedanyS.S. Systematic DFT studies of CO-Tolerance and CO oxidation on Cu-doped Ni surfaces.J. Mol. Graph. Model.202311810834310.1016/j.jmgm.2022.108343 36208590
     [Google Scholar]
  10. PieniazekS.N. ClementeF.R. HoukK.N. Sources of error in dft computations of c-c bond formation thermochemistries: π→σ transformations and error cancellation by dft methods.Angew. Chem.2008120407860786310.1002/ange.200801843
     [Google Scholar]
  11. GaoG. LiangC. Electrochemical and DFT studies of β-amino-alcohols as corrosion inhibitors for brass.Electrochim. Acta200752134554455910.1016/j.electacta.2006.12.058
     [Google Scholar]
  12. EisensteinO. MaronL. DFT studies of some structures and reactions of lanthanides complexes.J. Organomet. Chem.20026471-219019710.1016/S0022‑328X(01)01407‑3
     [Google Scholar]
  13. RbaaM. OubihiA. AnouarE.H. OuhssineM. AlmalkiF. HaddaT.B. ZarroukA. LakhrissiB. Synthesis of new heterocyclic systems oxazino derivatives of 8-Hydroxyquinoline: Drug design and POM analyses of substituent effects on their potential antibacterial properties.Chem. Data Collect.20192410030610.1016/j.cdc.2019.100306
     [Google Scholar]
  14. SyahiraF. YusofaM. JamalisaJ. ChanderbS. WahabaR.A. BhagwatbD.P. SankaranarayanancM. AlmalkiF.A. HaddadB.T. Psoralen derivatives: Recent advances of synthetic strategy and pharmacological properties.Antiinflamm. Antiallergy Agents Med. Chem.202019322223910.2174/1871523018666190625170802
     [Google Scholar]
  15. SajidZ. AhmadM. AslamS. AshfaqU.A. ZahoorA.F. SaddiqueF.A. ParvezM. HameedA. SultanS. ZgouH. HaddaT.B. Novel armed pyrazolobenzothiazine derivatives: Synthesis, x-ray crystal structure and pom analyses of biological activity against drug resistant clinical isolate of Staphylococcus aureus.Pharm. Chem. J.201650317218010.1007/s11094‑016‑1417‑y
     [Google Scholar]
  16. BabuV. DharmanP. BashaK.A. Microwave-assisted solution phase synthesis of novel pyridine carboxamides in neatwater and admet and protein-compounds interaction.Indian J. Chem.2023629910610.56042/ijc.v62i2.71260m
     [Google Scholar]
  17. DharmanP. BabuV. BashaK.A. A facile synthesis of novel 5‐substituted pyridine 2 carboxamide derivatives and their biological evaluation and 3D QSAR studies.J. Chin. Chem. Soc. 201966441542610.1002/jccs.201800035
     [Google Scholar]
  18. DharmanP. BabuV. BashaK.A. A facile synthesis of new 5-substituted pyridine-2-carboxamide derivatives.Indian J. Heterocycl. Chem.2021312191194https://connectjournals.com/01951.2021.31.191
     [Google Scholar]
  19. VisagamoorthyB. PrabuD. AnverK.B. Microwave-assisted solution phase synthesis of novel pyridine carboxamides in neat water and ADMET and protein-compounds interaction analysis and antibacterial activity.Indian J. Chem.20236299106
     [Google Scholar]
  20. HassanS.A. AzizD.M. AbdullahM.N. BhatA.R. DongreR.S. HaddaT.B. AlmalkiF.A. KawsarS.M.A. RahimanA.K. AhmedS. AbdellattifM.H. BerredjemM. SheikhS.A. JamalisJ. In vitro and in vivo evaluation of the antimicrobial, antioxidant, cytotoxic, hemolytic activities and in silico POM/DFT/DNA-binding and pharmacokinetic analyses of new sulfonamide bearing thiazolidin-4-ones.J. Biomol. Struct. Dyn.202311710.1080/07391102.2023.2226713 37402503
     [Google Scholar]
  21. HatzadeK. SheikhJ. TaileV. GhatoleA. IngleV. GencM. LahsasniS. Ben HaddaT. Antimicrobial/antioxidant activity and POM analyses of novel 7-o-β-d-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones.Med. Chem. Res.20152462679269310.1007/s00044‑015‑1326‑8
     [Google Scholar]
  22. MabkhotY. AldawsariF. ShowimanA.S. BarakatA. HaddaT. MubarakM. NazS. HaqU.Z. RaufA. Synthesis, bioactivity, molecular docking and POM analyses of novel substituted thieno[2,3-b]thiophenes and related congeners.Molecules20152021824184110.3390/molecules20021824 25621424
     [Google Scholar]
  23. MessaliM. AouadM.R. AliA.A.S. RezkiN. Ben HaddaT. HammoutiB. Synthesis, characterization, and POM analysis of novel bioactive imidazolium-based ionic liquids.Med. Chem. Res.20152441387139510.1007/s00044‑014‑1211‑x
     [Google Scholar]
  24. MessaliM. AouadM. SayedE.W. AliA.S.A. HaddaB.T. HammoutiB. New eco-friendly 1-alkyl-3-(4-phenoxybutyl) imidazolium-based ionic liquids derivatives: a green ultrasound-assisted synthesis, characterization, antibacterial activity and POM analyses.Molecules2014198117411175910.3390/molecules190811741 25153856
     [Google Scholar]
  25. LautreH.K. DasS. PatilK. YoussouffiH. HaddaB.T. PillaiA.K. Evaluation of antimicrobial and diureticactivity of schiffbasemetalcomplexes, part-ii.World J. Pharm. Pharm. Sci.20143612821297http://www.wjpps.com/wjpps_controller/abstract_id/1457
     [Google Scholar]
  26. MabkhotY.N. AlatibiA. SayedE.N. KhederN. WadoodA. RaufA. BawazeerS. ShowimanA.S. HaddaB.T. Experimental-computational evaluation of antimicrobial activity of some novel armed thiophene derivatives.Molecules201621222210.3390/molecules21020222 26901173
     [Google Scholar]
  27. TatarE. ŞenkardeşS. Selli̇tepeH.E. KüçükgüzelŞ.G. KaraoğluŞ.A. Bozdeveci̇A. ClercqD.E. PannecouqueC. HaddaB.T. Küçükgüzelİ. Synthesis, and prediction of molecular properties and antimicrobial activity of some acylhydrazones derived from $N$-(arylsulfonyl)methionine.Turk. J. Chem.20164051053410.3906/kim‑1509‑21
     [Google Scholar]
  28. BhatA.R. DongreR.S. AlmalkiF.A. BerredjemM. AissaouiM. TouzaniR. HaddaT.B. AkhterM.S. Synthesis, biological activity and POM/DFT/docking analyses of annulated pyrano[2,3-d]pyrimidine derivatives: Identification of antibacterial and antitumor pharmacophore sites.Bioorg. Chem.202110610448010.1016/j.bioorg.2020.104480 33279245
     [Google Scholar]
  29. JarrahpourA. HeiranR. SinouV. LatourC. BouktabD.L. BrunelM.J. SheikhJ. HaddaB.T. Synthesis of new β-lactams bearing the biologically important morpholine ring and pom analyses of their antimicrobial and antimalarial activities.Iran. J. Pharm. Res.20191813448 31089342
     [Google Scholar]
  30. BechlemK. AissaouiM. BelhaniB. RachediK.O. BouacidaS. BahadiR. DjouadS.E. MansourB.R. BouazizM. AlmalkiF. HaddaB.T. BerredjemM. Synthesis, X-ray crystallographic study and molecular docking of new α-sulfamidophosphonates: POM analyses of their cytotoxic activity.J. Mol. Struct.2020121012799010.1016/j.molstruc.2020.127990
     [Google Scholar]
  31. AlawadiD.Y. SaadehH.A. KaurH. GoyalK. SehgalR. HaddaB.T. ElSawyN.A. MubarakM.S. Metronidazolederivatives as a newclass of antiparasiticagents: Synthesis, biologicalactivity, and molecularpropertiesprediction.Med. Chem. Res.20152431196120910.1007/s00044‑014‑1197‑4
     [Google Scholar]
  32. AmirkhanovV. RaufA. HaddaT.B. OvchynnikovV. TrushV. SaleemM. RazaM. RehmanT. ZgouH. ShaheenU. FarghalyT.A. Pharmacophores modeling in terms of prediction of theoretical physicochemical properties and verification by experimental correlations of carbacylamidophosphates (caph) and sulfanylamidophosphates (saph) tested as new carbonic anhydrase inhibitors.Mini Rev. Med. Chem.201919121015102710.2174/1389557519666190222172757 30806314
     [Google Scholar]
  33. AwoyinkaO.A. BalogunI.O. OgunnowA.A. Phytochemical screening and in vitro bioactivity of Cnidoscolusa conitifolius (Euphorbiaceae).J. Med. Plants Res.200716365
     [Google Scholar]
  34. NCCLS Performance standards for antimicrobial disc susceptibility tests, (national committee for clinical laboratory standards, P A,); Publications, U S A, 1993
     [Google Scholar]
  35. AhmedS. JayathunaM.A. MahendiranD. BharathiS. RahimanK.A. HeterolepticSilver (I).Appl. Organomet. Chem.2022368e678210.1002/aoc.6782
     [Google Scholar]
  36. K’tirH. AmiraA. BenzaidC. AoufZ. BenharounS. ChemamY. ZerroukiR. AoufN.E. Synthesis, bioinformatics and biological evaluation of novel α-aminophosphonates as antibacterial agents: DFT, molecular docking and ADME/T studies.J. Mol. Struct.2022125013163510.1016/j.molstruc.2021.131635
     [Google Scholar]
  37. BharathiS. MahendiranD. AhmedS. RahimanA.K. invitroanti-proliferative, and in silico ribonucleotide reductase and pharmacokineticsstudies of heterolepticsilver (i).J. Trace Elem. Med. Biol.20237912721110.1016/j.jtemb.2023.127211 37263062
     [Google Scholar]
  38. BahadiR. BerredjemM. BenzaidC. BoucharebF. DekirA. DjendiM.L. OualiI.M. BoussakerM. BouacidaS. BhatA.R. AhmedS. BachariK. RedjemiaR. Efficient synthesis, crystallography study, antibacterial/antifungal activities, DFT/ADMET studies and molecular docking of novel α-aminophosphonates.J. Mol. Struct.2023128913584910.1016/j.molstruc.2023.135849
     [Google Scholar]
  39. AhmedS. MahendiranD. BhatA.R. RahimanA.K. Theoretical, in vitro antiproliferative, and in silico molecular docking and pharmacokinetics studies of heteroleptic nickel(ii) and copper(ii) complexes of thiosemicarbazone‐based ligands and pefloxacin.Chem. Biodivers.2023209e20230070210.1002/cbdv.202300702 37528701
     [Google Scholar]
  40. AmuthakalaS. BharathiS. RahimanK.A. Semicarbazone and thiosemicarbazone appended 4-diethylamino-2 hydroxybenzyl compounds as highly selective bifunctional chemosensors: An experimental and computational approach.Inorg. Chim. Acta202354612130210.1016/j.ica.2022.121302
     [Google Scholar]
  41. YanA. GasteigerJ. Prediction of aqueous solubility of organic compounds based on a 3D structure representation.J. Chem. Inf. Comput. Sci.200343242943410.1021/ci025590u 12653505
     [Google Scholar]
  42. ErtlP. RohdeB. SelzerP. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties.J. Med. Chem.200043203714371710.1021/jm000942e 11020286
     [Google Scholar]
/content/journals/mc/10.2174/0115734064293464240405050455
Loading
Computational Chemistry: Prediction of Compound Accessibility of Targeted Synthesized Compounds
Med. Chem. 21, 334 (2025); https://doi.org/10.2174/0115734064293464240405050455
/content/journals/mc/10.2174/0115734064293464240405050455
/content/journals/mc/10.2174/0115734064293464240405050455
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): ADME; carboxamides; computational chemistry; lipinski's rule; molinspiration; pharmacokinetics

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