Synthesis of novel α-aminophosphonates under microwave irradiation, biological evaluation as antiproliferative agents and apoptosis inducers
- 37 Downloads
The synthesis of two series of α-aminophosphonates was achieved by Microwave Irradiation (MW), using the one-pot Kabachnik–Fields reaction. Based on a green chemistry approach, the reactions were carried out using ethanol as the only solvent and without any catalyst, and short reaction times (20–40 min), in variable yields. Both series were tested to determine their cell proliferation inhibition activity in MDA-MB-231, MCF-7 and MCF-10A cell lines. Ethyl 4-(((diphenoxyphosphoryl)(4-(diphenylamino)phenyl)methyl)amino) benzoate 4e and diphenyl (((4-(((S)-2-hydroxy-1-phenylethyl)carbamoyl)phenyl)amino)(4-hydroxyphenyl)methyl)phosphonate 6b, showed cell proliferation inhibition activity only in the cancer cell line MCF-7 and no effect on the normal cell line MFC-10A, both compounds caused cell death by inducing apoptosis.
KeywordsAminophosphonates Green synthesis Kabachnik–Fields Cell proliferation inhibition activity Apoptosis
The authors thank the National Council for Science and Technology (CONACYT) for its financial support via Project 180854. ELLC, also thanks CONACYT for a Graduate Scholarship 229877.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Berridge MV, Tan AS (1993) Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction. Arch Biochem Biophys 303:474–482. https://doi.org/10.1006/abbi.1993.1311 CrossRefGoogle Scholar
- Bhagat S, Chakraborti AK (2007) An extremely efficient three-component reaction of aldehydes/ketones, amines, and phosphites (Kabachnik−Fields reaction) for the synthesis of α-aminophosphonates catalyzed by magnesium perchlorate. J Org Chem 72:1263–1270. https://doi.org/10.1021/jo062140i CrossRefGoogle Scholar
- Guida M, Tommasi S, Strippoli S et al. (2018) The search for a melanoma-tailored chemotherapy in the new era of personalized therapy: a phase II study of chemo-modulating temozolomide followed by fotemustine and a cooperative study of GOIM (Gruppo Oncologico Italia Meridionale). BMC Cancer 18:552. https://doi.org/10.1186/s12885-018-4479-2 CrossRefGoogle Scholar
- Hudson HR, Lee RJ (2014) A brief review of the anticancer activity of α-aminophosphonic acid derivatives and a report on the in vitro activity of some dialkyl α-aryl- (or Heteroaryl)-α-(diphenylmethylamino)methanephosphonates. Phosphorus Sulfur Silicon Relat Elem 189:1149–1155. https://doi.org/10.1080/10426507.2014.905781 CrossRefGoogle Scholar
- Magedov IV, Manpadi M, Van slambrouck S et al. (2007) Discovery and investigation of antiproliferative and apoptosis-inducing properties of new heterocyclic podophyllotoxin analogues accessible by a one-step multicomponent synthesis. J Med Chem 50:5183–5192. https://doi.org/10.1021/jm070528f CrossRefGoogle Scholar
- Mirzaei M, Eshghi H, Rahimizadeh M et al. (2015) An eco-friendly three component manifold for the synthesis of α -aminophosphonates under catalyst and solvent-free conditions, X-ray characterization and their evaluation as anticancer agents. J Chin Chem Soc 62:1087–1096. https://doi.org/10.1002/jccs.201500250 CrossRefGoogle Scholar
- Mungara AK, Park Y-K, Lee KD (2012) Synthesis and antiproliferative activity of novel α-aminophosphonates. Chem Pharm Bull 60:1531–1537Google Scholar
- Riss TL, Moravec RA, Niles AL et al. (2016) Cell viability assays. In Assay Guidance Manual [Internet eBook]. Eli Lilly & Company and the National Center for Advancing Translational Sciences. http://www.ncbi.nlm.nih.gov/books/NBK144065/
- Venkata Ramana K, Rasheed S, Chandra Sekhar K et al. (2012) One-pot and catalyst-free synthesis of novel α-aminophosphonates under microwave irradiation and their biological activity. Der Pharm Lett 4:456–463Google Scholar