Synthesis of New 4-Chloro-6-Methylpyrimidin-2-yl-Aminophosphonates as Potential DU145 and A549 Cancer Cell Inhibitors

Author(s): Gajjala Raghavendra Reddy, Chinta Raveendra Reddy, Gopireddy Venkata Subba Reddy, Pasupuleti Visweswara Rao, Meenakshisundaram Swaminathan, Balam Satheeh Krishna, Cirandur Suresh Reddy*

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 4 , 2020

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Graphical Abstract:


A series of new α-aminophosphonates containing potential anticancer active 4-chloro-6- methylpyrimidin-2-amino pharmacophore were synthesized.

Background: α-Aminophosphonates are of growing interest to the researchers due to their biological activities. Besides aminophosphoryl functionality, which is responsible for the vital activity, incorporation of a captivating pharmacophore on it will definitely enrich its activity.

Objective: Erstwhile many of the reported α-aminophosphonates impregnated with bioactive heterocycles like quinazoline, chromene, pyrazole, furan and thiophene were used as anticancer drugs, and we are intended to enhance the anticancer potentiality of α-aminophosphonates by substituting a new 4-chloro-6-methylpyrimidin-2-yl group into its structure, specifically on nitrogen atom.

Methods: Title compounds were synthesized by Kabachnik-Fields reaction by using sulfated Titania, a solid acid catalyst that is encompassed with high density of Lewis acidic reaction sites. The series of synthesized compounds were screened for in vitro anti-cancer activity and their ADMET, QSAR and drug properties studied.

Results: Structures of all the title compounds synthesized in high yields were confirmed by spectral & elemental analyses. Their anti-cancer screening studies on various cell lines and evaluation of other properties revealed their potentiality towards the inhibition of growth of DU145 & A549 cell lines.

Conclusion: The substitution of 4-chloro-6-methylpyrimidin-2-amino moiety on to the amino functionality of the α-aminophosphonates is a critical task invariably due to the substitutions that are located on α-carbon. As such, this substitution had increased the scope for growth inhibition of DU145 and A549 cancer cells.

Keywords: Kabachnik-Fields reaction, 4-chloro-6-methylpyrimidin-2-amine, sulfated Titania, DU145 cell lines, A549 cell lines, in vitro anti-cancer activity, QSAR studies, ADMET properties.

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Year: 2020
Published on: 29 March, 2019
Page: [396 - 410]
Pages: 15
DOI: 10.2174/1570180816666190329223207
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