Skip to content
2000
Volume 21, Issue 19
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

Infections caused by parasites continue to pose a risk to both human and animal health. The most popular drug classes for treating these infections include thiabendazole, imidazo-thiazoles, levamisole, and avermectins (obtained from the fermentation products of Streptomyces avermitilis). The majority of bacteria that we come across in any form of infection are successfully combatted by β- lactam medicines. Similar to the majority of treatments, problems with treatment resistance to these drugs have evolved over time, necessitating the development of new anthelmintic medications. This study aims to investigate a series of quinazoline-bearing β-lactam rings as potent anthelmintic agents.

Methods

The new series of quinazoline bearing β-lactam was synthesized reaction of 5-bromo anthranilic acid with acetic anhydride to produce 6-bromo-2-methyl-4H-benzo (1,3) oxazin-4-one which was then converted into 3-amino-6-bromo-2-methylquinazolin-4(3H)-one by the reaction of hydrazine hydrate in the presence of anhydrous pyridine. The resultant intermediate then goes through a Schiff reaction with various aromatic aldehydes, followed by reflux with triethylamine and chloroacetyl chloride.

Results

Structural assignments of these compounds have been made by elemental analysis, FTIR,1HNMR and Mass spectral data and the purity of the compounds was determined by TLC. Molecular docking studies showed the effective binding of synthesized derivatives with tubulin in comparison to the orientation of standard drugs. The anthelmintic activities of all the synthesized compounds were evaluated separately for their possible using common Indian earthworm .

Conclusion

A total of ten derivatives of quinazoline bearing β-lactam ring were designed, synthesized and evaluated against the Indian earthworm . Out of ten derivatives, SQD2 and SQD6, showed promising anthelmintic activity when compared with standard drugs albendazole and piperazine citrate.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/lddd/10.2174/1570180820666230901121339
2025-02-14
2025-08-18

  • From This Site

    /content/journals/lddd/10.2174/1570180820666230901121339
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. RainovaI. HarizanovR. KaftandjievI. TsvetkovaN. MikovO. KanevaE. Kaneva, parasitic diseases in bulgaria in between 2013-2014.Balkan Med. J.2018351616710.4274/balkanmedj.2017.0167 28903890
     [Google Scholar]
  2. PandeyS. LoA.L. ShresthaR.B. Intestinal parasitic infections among school children of Northern Kathmandu, Nepal.Asian Pac. J. Trop. Dis.20155S1S89S9210.1016/S2222‑1808(15)60864‑7
     [Google Scholar]
  3. PinkR. HudsonA. MourièsM.A. BendigM. Opportunities and challenges in antiparasitic drug discovery.Nat. Rev. Drug Discov.20054972774010.1038/nrd1824 16138106
     [Google Scholar]
  4. AtjanasuppatK. WongkhamW. MeepowpanP. KittakoopP. SobhonP. BartlettA. WhitfieldP.J. In vitro screening for anthelmintic and antitumour activity of ethnomedicinal plants from Thailand.J. Ethanopharmacol.2009123479482
     [Google Scholar]
  5. FriedmanP.A. PlatzerE.G. Interaction of anthelmintic benzimidazoles with AscarisSuum embryonic tubulin.Biochim. Biophys. Acta, Gen. Subj.1980630227127810.1016/0304‑4165(80)90431‑6 7388055
     [Google Scholar]
  6. EwesW.A. ElmorsyM.A. El-MesseryS.M. NasrM.N.A. Synthesis, biological evaluation and molecular modeling study of [1,2,4]-Triazolo[4,3-c]quinazolines: New class of EGFR-TK inhibitors.Bioorg. Med. Chem.202028711537310.1016/j.bmc.2020.115373 32085964
     [Google Scholar]
  7. AllamH.A. AlyE.E. FaroukA.K.B.A.W. El KerdawyA.M. RashwanE. AbbassS.E.S. Design and synthesis of some new 2,4,6-trisubstituted quinazoline EGFR inhibitors as targeted anticancer agents.Bioorg. Chem.202098103726
     [Google Scholar]
  8. DasD. XieL. WangJ. ShiJ. HongJ. In vivo efficacy studies of novel quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors, in lung cancer xenografts (NCI-H1975) mice models.Bioorg. Chem.20209910379010.1016/j.bioorg.2020.103790 32279037
     [Google Scholar]
  9. RahmannejadiN. YavariI. KhabnadidehS. Synthesis and antitumor activities of novel bis‐quinazolin‐4(3 H)‐ones.J. Heterocycl. Chem.202057397898210.1002/jhet.3749
     [Google Scholar]
  10. LeY. GanY. FuY. LiuJ. LiW. ZouX. ZhouZ. WangZ. OuyangG. YanL. Design, synthesis and in vitro biological evaluation of quinazolinone derivatives as EGFR inhibitors for antitumor treatment.J. Enzyme Inhib. Med. Chem.202035155556410.1080/14756366.2020.1715389 31967481
     [Google Scholar]
  11. LiW. ChenS.Y. HuW.N. ZhuM. LiuJ.M. FuY.H. WangZ.C. OuYangG.P. Design, synthesis, and biological evaluation of quinazoline derivatives containing piperazine moieties as antitumor agents.J. Chem. Res.2020449-1053654210.1177/1747519820910384
     [Google Scholar]
  12. M, Voskoboinik, O., O.M.; Kazunin, I.; Nosulenko, I.; Shishkina, S.; Kovalenko, S. Substituted pyrrolo[1,2-a][1,2,4]triazolo-([1,2,4]triazino-)[c]quinazoline-4A(5a)-propanoic acids: Synthesis, spectral characteristics and anti-inflammatory activity. Vopr. Khimii I Khimicheskoi Tekhnologii.,20202020617010.32434/0321‑4095‑2020‑128‑1
     [Google Scholar]
  13. RajputC.S. SinghalS. Synthesis, characterization and anti-inflammatory activities of new quinazolinone analogs.J. Pharm. 201320131710.1155/2013/907525 26556002
     [Google Scholar]
  14. PoojariS. ParmeshwarN.P. KrishnamurthyG. Jithendra KumaraK.S. Sunil KumarN. SathishN. Anti-inflammatory, antibacterial and molecular docking studies of novel spiro-piperidine quinazolinone derivatives.J. Taibah Univ. Sci.201711349751110.1016/j.jtusci.2016.10.003
     [Google Scholar]
  15. NangareA. RandiveD. BarkadeG. Synthesis and biological evaluation of novel quinazoline derivatives as anticancer, antibacterial and antifungal agents.Bull. Env. Pharmacol. Life Sci20211017919010.1016/j.ejmech.2010.06.013
     [Google Scholar]
  16. DixitA. PathakD. SharmaG.K. Synthesis, antibacterial and antioxidant activity of novel 12-(N-arylmethaniminyl)indolo[1,2-c]quinazolines.J. Pharm. Res.201923358459510.12991/jrp.2019.166
     [Google Scholar]
  17. AntipenkoL. KarpenkoA. KovalenkoS. KatsevA. Komarovska-PorokhnyavetsE. NovikovV. ChekotiloA. Synthesis of new 2-thio-[1,2,4]triazolo[1,5-c]quinazoline derivatives and its antimicrobial activity.Chem. Pharm. Bull. 200957658058510.1248/cpb.57.580 19483337
     [Google Scholar]
  18. JatavV. KashawS. MishraP. GuptaV. Synthesis and antimicrobial activity of some new 3-[5-(4-substituted) phenyl-1, 3, 4-oxadiazole-2yl]-2-styryl quinazoline- 4(3H)-ones.Med. Chem. Res.20081720521110.1007/s00044‑007‑9047‑2
     [Google Scholar]
  19. WangM. ZhangG. WangY. WangJ. ZhuM. CenS. WangY. Design, synthesis and anti-influenza A virus activity of novel 2,4-disubstituted quinazoline derivatives.Bioorg. Med. Chem. Lett.2020301112714310.1016/j.bmcl.2020.127143 32273213
     [Google Scholar]
  20. RothanH. FarajF.L. TeohT.C. YusofR. Novel Quinazoline derivatives inhibited HCV Serine protease and viral replication in Huh-7 cells.bioRxiv201967131310.1101/671313
     [Google Scholar]
  21. XieD. ShiJ. ZhangA. LeiZ. ZuG. FuY. GanX. YinL. SongB. HuD. Syntheses, antiviral activities and induced resistance mechanisms of novel quinazoline derivatives containing a dithioacetal moiety.Bioorg. Chem.20188043344310.1016/j.bioorg.2018.06.026 29986188
     [Google Scholar]
  22. HeilM.L. CosfordN.D. ArdeckyR. ZouJ. Quinazolinone analogs and use of quinazolinone analogs for treating or preventing certain Viral infection. U.S. Patent 10,611,7332017
     [Google Scholar]
  23. JadhavarP.S. PatelK.I. DhameliyaT.M. SahaN. VajaM.D. KrishnaV.S. SriramD. ChakrabortiA.K. Benzimidazoquinazolines as new potent anti-TB chemotypes: Design, synthesis, and biological evaluation.Bioorg. Chem.20209910377410.1016/j.bioorg.2020.103774 32224336
     [Google Scholar]
  24. GawadJ. BondeC. Design, synthesis and biological evaluation of novel 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives as a potential DprE1 inhibitors.J. Mol. Struct.2020121712839410.1016/j.molstruc.2020.128394
     [Google Scholar]
  25. LupienA. FooC.S.Y. SavinaS. VocatA. PitonJ. MonakhovaN. BenjakA. LamprechtD.A. SteynA.J.C. PetheK. MakarovV.A. ColeS.T. New 2-Ethylthio-4-methylaminoquinazoline derivatives inhibiting two subunits of cytochrome bc1 in Mycobacterium tuberculosis.PLoS Pathog.2020161e100827010.1371/journal.ppat.1008270 31971990
     [Google Scholar]
  26. Al-SalahiR. TaieH.A.A. BakheitA.H. MarzoukM. AlmehiziaA.A. HerqashR. AbuelizzH.A. Antioxidant activities and molecular docking of 2-thioxobenzo[g]quinazoline derivatives.Pharmacol. Rep.201971469570010.1016/j.pharep.2019.04.003 31207430
     [Google Scholar]
  27. AlmehiziaA.A. AbuelizzH.A. TaieH.A.A. ElHassaneA. MarzoukM. Al-SalahiR. Investigation the antioxidant activity of benzo[g]triazoloquinazolines correlated with a DFT study.Saudi Pharm. J.201927113313710.1016/j.jsps.2018.09.006 30662316
     [Google Scholar]
  28. LakhanR. SinghO.P. SinghJ.R.L. Studies on 4 (3H)-quinazolinone derivatives as anti-malarials.J. Indian Chem. Soc.198764316318
     [Google Scholar]
  29. El-AzabA.S. Abdel-AzizA.A.M. BuaS. NocentiniA. AlSaifN.A. AlanaziM.M. El-GendyM.A. AhmedH.E.A. SupuranC.T. S-substituted 2-mercaptoquinazolin-4(3H)-one and 4-ethylbenzensulfonamides act as potent and selective human carbonic anhydrase IX and XII inhibitors.J. Enzyme Inhib. Med. Chem.202035173374310.1080/14756366.2020.1742117 32189526
     [Google Scholar]
  30. MishraM. MishraV.K. KashawV. AgrawalR.K. KashawS.K. Novel quinazoline chalcone hybrids as antiplasmodium agents: Synthesis, biological evaluation and molecular docking.Int. J. Adv. Sci. Res.2020118599
     [Google Scholar]
  31. MehriziA.A. TahghighiA. ZakeriS. In vitro anti-plasmodial activity of new synthetic derivatives of 1-(heteroaryl)-2- ((5-nitroheteroaryl)methylene) hydrazine.Asian Pac. J. Trop. Med.202114312813810.4103/1995‑7645.306740
     [Google Scholar]
  32. AmraneD. GellisA. HutterS. PrieriM. VerhaegheP. AzasN. VanelleP. PrimasN. Synthesis and antiplasmodial evaluation of 4-carboxamido- and 4-alkoxy-2-trichloromethyl quinazolines.Molecules20202517392910.3390/molecules25173929 32867402
     [Google Scholar]
  33. MalamasM.S. MillenJ. Quinazolineacetic acids and related analogs as aldose reductase inhibitors.J. Med. Chem.19913441492150310.1021/jm00108a038 1901912
     [Google Scholar]
  34. TiwariP. SinghG. ShrivastavD. BaghelA. PatelR. PatidarV. Synthesis and biological evaluation studies of novel benzo1,3-diazine derivatives as anti-inflammatory agents.Eur. J. Mol. Clin. Med.202070146504665
     [Google Scholar]
  35. SaiK.G.D. GuduruS.K. SirishaK. SanthoshiK.S. Synthesis, characterization and evaluation of new thiazole derivatives as anthelmintic agents.Ind J. Chem. Sect. B2021604616623
     [Google Scholar]
  36. DewanganD. VaishnavY. MishraA. JhaA.K. VermaS. BadwaikH. Synthesis, molecular docking, and biological evaluation of Schiff base hybrids of 1,2,4-triazole-pyridine as dihydrofolate reductase inhibitors.CRPHAR2021210002410.1016/j.crphar.2021.100024 34909659
     [Google Scholar]
  37. PatraP.K. PatraC.N. PattnaikS. Antifungal and anthelmintic activity of some novel pyrazole derivative.Asian J. Res. Chem2014719298
     [Google Scholar]
  38. KenchappaR. BodkeY.D. TelkarS. ArunaS.M. Antifungal and anthelmintic activity of novel benzofuran derivatives containing thiazolo benzimidazole nucleus: An in vitro evaluation.J. Chem. Biol.2017101112310.1007/s12154‑016‑0160‑x 28101251
     [Google Scholar]
/content/journals/lddd/10.2174/1570180820666230901121339
Loading
Synthesis, Computational Study of β-lactam Derivatives Bearing Quinazoline Schiff Bases as Anthelmintics
Letters in Drug Design & Discovery 21, 4994 (2024); https://doi.org/10.2174/1570180820666230901121339
/content/journals/lddd/10.2174/1570180820666230901121339
/content/journals/lddd/10.2174/1570180820666230901121339
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): Albendazole; anthelmintic activity; molecular docking; piperazine citrate; quinazoline; schiff base

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