Skip to main content

Advertisement

Log in

Investigation of some diethyl (4-(dimethylamino)-2,5-dihydro-2,5-dioxo-1-phenyl-1H-pyrrol-3-yl)(hydroxy)methylphosphonate derivatives for In silico pharmacokinetic profile and In vitro anticancer activity

  • Original Paper
  • Published:
Chemical Papers Aims and scope Submit manuscript

Abstract

Maleimide is an important pharmacophore having several biological activities. Maleimide derivatives linked with hydroxy phosphonate moiety had been investigated for their antimicrobial activity. As an extension to the previous work, we could perform in silico screening of the pharmacokinetic profile and in vitro anticancer activity determination of these compounds. In silico pharmacokinetic (ADMET) profiles were explored. Further, in vitro anticancer activities were carried out on MDA-MB-231, MCF-7, and A-549 cell lines to propose a possible role of these derivatives in the treatment of cancer. All the molecules (5a-5g) exhibited desired physicochemical properties needed for oral bioavailability. All the synthesized molecules exhibited high GI absorption which is the most needed property for drug development. In acute toxicity predictions, all the molecules fall under toxicity class IV. All synthesized molecules showed a preference for cell growth inhibition against breast (MDA-MB-231 and MCF-7) and lung (A-549) cancer cell lines. Amongst all the molecules, 5d exhibited most potent activity (GI50 (μM)] against MDA-MB-231 (13.66 ± 0.038), A-549 (13.62 ± 0.041), MCF-7 (10.81 ± 0.038) which possess trifluoro substitution at meta-position. From present investigation, we report compound 5d [diethyl (4-(dimethylamino)-1-(3-(trifluoromethyl)phenyl)-2,5-dihydro-2,5-dioxo-1H-pyrrol-3-yl)-(hydroxy)methylphosphonate] as promising anti-breast and lung-cancer agent. The cellular toxicity of the novel compounds was also evaluated using normal mouse embryonic fibroblast (NIH/3T3) cell lines. From this study, maleimide linked with hydroxy phosphonate can be treated as a lead nucleus for further development of novel anticancer agents using different in vitro and in vivo models.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

Download references

Acknowledgements

SP and KJ wish to acknowledge the financial support provided by DST SERB (ECR/2016/001962) for the research work. NSP thanks Principal and Management R D and S H National College and S W A Science College for infrastructure facilities.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Nilesh S. Patil or Kapil Juvale.

Ethics declarations

Conflict of interest

The authors declared that there are no competing interests exist.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 4255 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Puri, S., Patil, N.S. & Juvale, K. Investigation of some diethyl (4-(dimethylamino)-2,5-dihydro-2,5-dioxo-1-phenyl-1H-pyrrol-3-yl)(hydroxy)methylphosphonate derivatives for In silico pharmacokinetic profile and In vitro anticancer activity. Chem. Pap. 76, 6713–6721 (2022). https://doi.org/10.1007/s11696-022-02329-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11696-022-02329-3

Keywords

Navigation