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

[ Vol. 17 , Issue. 4 ]

Author(s):

Gajjala Raghavendra Reddy, Chinta Raveendra Reddy, Gopireddy Venkata Subba Reddy, Pasupuleti Visweswara Rao, Meenakshisundaram Swaminathan, Balam Satheeh Krishna and Cirandur Suresh Reddy*   Pages 396 - 410 ( 15 )

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.

Affiliation:

Department of Chemistry, Jawaharlal Nehru Technological University Ananthapur, Andhra Pradesh, Ananthapuramu 515 002, Department of Science & Humanities, NBKR Institute of Science & Technology, Andhra Pradesh, Vidyanagar 524 413, Department of Chemistry, JNTUA College of Engineering, Andhra Pradesh, Pulivendula 516 390, Department of Biomedical Sciences and Therapeutics, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah 88400, Nanomaterials Laboratory, Department of Chemistry, Kalasalingam Academy of Research and Education, Tamil Nadu, Krishnankoil 626 126, Department of Chemistry, Sri Venkateswara University, Andhra Pradesh, Tirupati 517 502, Department of Chemistry, Sri Venkateswara University, Andhra Pradesh, Tirupati 517 502

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