Synthesis and characterization some new dioxaphosphorinanes as anticancer agents

Document Type : Original Article

Authors

1 Faculty of basic sciences, Lorestan university

2 Islamic Azad University of Pharmaceutical Science Branch, Tehran, Iran

Abstract

Some new dioxaphosphorinane derivatives were synthesized with general formula RC(O)NHP(O)OCH2C(CH3)2CH2O [R = 4-CH3OC6H4 (1), 4-NO2C6H4 (2), C6H5 (3), 4-CH3OC6H4NH (4)]. The structures of the compounds were established by IR, 1H NMR, 13C, 31P NMR spectroscopy. Two separate signals for CH3 groups on dioxaphosphorinane rings and the Hequatorial and Haxial atoms of CH2 groups in these compounds demonstrate that the synthesized compounds are toward one chair conformation. Besides, all newly synthesized compounds and cyclophosphamide (standard drug, CP) were screened for their anticancer activity against three human cell lines, breast cancer (MCF-7), prostate cancer (PC-3) and cervical cancer (HeLa). Results indicated that compound 4 with phosphinourea backbone and methoxy substitute was found to be the most active with IC50 of 0.03±0.007, 0.011±0.003, and 0.05±0.009 (nM) against MCF-7, PC‐3, and HeLa cell lines, respectively. Further, the structure-activity relationship (SAR) indicates that high lipophilic nature and the molecular volume of 4 have the direct order with its activity.

Graphical Abstract

Synthesis and characterization some new dioxaphosphorinanes as anticancer agents

Keywords

References

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Iranian Journal of Chemistry
Volume 2, Issue 2 - Serial Number 3
February 2020
Pages 127-132

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History

  • Receive Date: 02 December 2018
  • Revise Date: 23 April 2019
  • Accept Date: 14 February 2020

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