Skip to content
2000
Volume 25, Issue 3
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Finding the most perfect drug candidates in the fields of drug discovery and medicinal chemistry will remain the main interest of drug designers. This concern necessitates organic and medicinal chemists, in most examples, to precisely design and search for drug candidates that are very analogous to the present effective drugs with solving, mainly, their proven critical pharmacological and clinical issues through slightly changing one or two atoms of the principal functional skeletons of the molecules of these present therapeutics by atom swapping, removal, and/or addition procedures in organic chemical synthesis. This accurate modern chemicosimilarity tactic in drug discovery surely saves time while keeping us very close, or sometimes highly superior, to the parent pharmacophoric bioactivity (, keeping considerable analogy to the parent therapeutic molecule). From this perspective and logic, the science of skeletal editing of molecules (, skeletal molecular editing) arose in the era of artificial intelligence (AI) and its dramatic predictions. As a pioneer in this modern branch in pharmaceutical and therapeutic organic chemistry, in this up-to-date minireview and perspective article, an attempt was made to introduce skeletal editing and its synthetic surgeries (over molecules) to the audience (including irrelevant readers) in a simpler and more attractive way as a novel chemical technology, highlighting the previous synthetic trials (in general), demonstrating the three main techniques, and, finally, discussing the future therapeutic needs and scenarios from a medicinal chemist's viewpoint.

© 2025 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575316229240611113946
2024-06-12
2025-01-15
Loading full text...

Full text loading...

/deliver/fulltext/mrmc/25/3/MRMC-25-3-03.html?itemId=/content/journals/mrmc/10.2174/0113895575316229240611113946&mimeType=html&fmt=ahah

References

  1. FicarraF. SilviM. Atom-swap chemistry could aid drug discovery.Nature20236237985363710.1038/d41586‑023‑03297‑8 37914944
    [Google Scholar]
  2. RabieA.M. Four three-winged nitrogenous heterocyclic derivatives of citric acid scaffold: The first synthesis and characterization of these newly discovered fan-like compounds.Russ. J. Org. Chem.202157341742110.1134/S1070428021030131
    [Google Scholar]
  3. RabieA.M. Design, synthesis, and characterization of novel series of pharmacologically-important sperm-shaped amphiphilic heterocyclic compounds derived from natural palmitic acid.Nat. Resour. Hum. Health20222228729210.53365/nrfhh/144888
    [Google Scholar]
  4. NashaanF.A. Al-RawiM.S. AlhammerA.H. RabieA.M. TommaJ.H. Synthesis, characterization, and cytotoxic activity of some imides from galloyl hydrazide.Eurasian Chem. Commun.202241096697510.22034/ecc.2022.340135.1453
    [Google Scholar]
  5. RabieA.M. TantawyA.S. BadrS.M.I. Design, synthesis, and biological evaluation of novel 5-substituted-2-(3,4,5-trihydroxyphenyl)-1,3,4-oxadiazoles as potent antioxidants.Am. J. Org. Chem.201662548010.5923/j.ajoc.20160602.02
    [Google Scholar]
  6. MohammedY.H.I. ShamkhI.M. AlharthiN.S. ShanawazM.A. AlzahraniH.A. JabbarB. BeighS. AlghamdiS. AlsakhenN. KhidirE.B. AlhuthaliH.M. KaramallaT.H.E. RabieA.M. Discovery of 1-(5-bromopyrazin-2-yl)-1-[3-(trifluoromethyl)benzyl]urea as a promising anticancer drug via synthesis, characterization, biological screening, and computational studies.Sci. Rep.20231312282410.1038/s41598‑023‑44662‑x 38129413
    [Google Scholar]
  7. RabieA.M. Accurate conventional and microwave-assisted synthesis of galloyl hydrazide.MethodsX2020710073710.1016/j.mex.2019.11.010 32025504
    [Google Scholar]
  8. RabieA.M. Improved synthesis of the anti-SARS-CoV-2 investigational agent (E)-N-(4-cyanobenzylidene)-6-fluoro-3-hydroxypyrazine-2-carboxamide (Cyanorona-20).Rev. Chim.2022734697510.37358/RC.22.4.8555
    [Google Scholar]
  9. RabieA.M. TantawyA.S. BadrS.M.I. Design, synthesis, and biological evaluation of new 5-substituted-1,3,4-thiadiazole-2-thiols as potent antioxidants.Researcher2018107214310.7537/marsrsj100718.04
    [Google Scholar]
  10. QianY. AllegrettaG. JanardhananJ. PengZ. MahasenanK.V. LastochkinE. GozunM.M.N. TejeraS. SchroederV.A. WolterW.R. FeltzerR. MobasheryS. ChangM. Exploration of the structural space in 4(3H)-quinazolinone antibacterials.J. Med. Chem.202063105287529610.1021/acs.jmedchem.0c00153 32343145
    [Google Scholar]
  11. PeplowM. ‘Almost magical’: Chemists can now move single atoms in and out of a molecule’s core.Nature20236187963212410.1038/d41586‑023‑01735‑1 37259000
    [Google Scholar]
  12. ChengQ. BhattacharyaD. HaringM. CaoH. Mück-LichtenfeldC. StuderA. Skeletal editing of pyridines through atom-pair swap from CN to CC.Nat. Chem.202416574174810.1038/s41557‑023‑01428‑2 38238464
    [Google Scholar]
  13. WooJ. ChristianA.H. BurgessS.A. JiangY. MansoorU.F. LevinM.D. Scaffold hopping by net photochemical carbon deletion of azaarenes.Science2022376659252753210.1126/science.abo4282 35482853
    [Google Scholar]
  14. MartinB.S. MaD. SaitoT. GallagherK.S. DaiM. Concise total synthesis of complanadine A enabled by pyrrole-to-pyridine molecular editing.Synthesis202456110711710.1055/a‑2107‑5159
    [Google Scholar]
  15. LiuZ. SivaguruP. NingY. WuY. BiX. Skeletal editing of (hetero)arenes using carbenes.Chem. - Eur. J.20232942e20230122710.1002/chem.202301227 37230933
    [Google Scholar]
  16. PacesaM. PeleaO. JinekM. Past, present, and future of CRISPR genome editing technologies.Cell202418751076110010.1016/j.cell.2024.01.042 38428389
    [Google Scholar]
  17. RabieA.M. RNA: The most attractive target in recent viral diseases.Chem. Biol. Drug Des.20241031e1440410.1111/cbdd.14404 38092663
    [Google Scholar]
  18. JoynsonB.W. BallL.T. Skeletal editing: Interconversion of arenes and heteroarenes.Helv. Chim. Acta20231063e20220018210.1002/hlca.202200182
    [Google Scholar]
  19. FuJ. NakataY. ItohH. PantheeS. HamamotoH. SekimizuK. InoueM. Molecular editing enhances oxidation resistance of menaquinone‐targeting antibiotics lysocin E and WAP‐8294A2.Chem. - Eur. J.20232947e20230122410.1002/chem.202301224 37328428
    [Google Scholar]
  20. ZhangZ. ZhangW. HouZ.-W. LiP. WangL. Electrophilic halospirocyclization of N-benzylacrylamides to access 4-halomethyl-2-azaspiro[4.5]decanes.J. Org. Chem.20238819136101362110.1021/acs.joc.3c01315 37694951
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575316229240611113946
Loading
/content/journals/mrmc/10.2174/0113895575316229240611113946
Loading

Data & Media loading...

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