Synthesis of Novel α‐Aminophosphonate Derivatives, Biological Evaluation as Potent Antiproliferative Agents and Molecular Docking

Abstract

A series of novel fluorine containing α‐aminophosphonate derivatives (4 a–4 q) were synthesized in excellent yield and high purity. All these novel Fluorinated α‐aminophosphonate compounds were screened for antiproliferative and apoptosis activity on human non small cell lung carcinoma cells (A549) and human skin melanoma cells (SK‐MEL‐2). Compounds 4 a, 4 b, 4 c, 4 f, 4 i, 4 j and 4 m were found to be more active antiproliferative agent against A549 and SK‐MEL‐2 cells with IC50 value 0.22 to 1.25 μM. Molecular docking study related to binding affinity and binding mode analysis showed that synthesized compounds had potential to inhibit human Topoisomerase IIa enzyme system. Flow cytometric study showed some of these derivatives also induced cell apoptosis and arrest cell cycle at G1 and at G2/M phase. Overall, this study provides future perspective of lead candidate for the future anticancer drug discovery initiatives.

2-Hydroxymethyl-18-crown-6 as an efficient organocatalyst for α - aminophosphonates synthesized under eco-friendly conditions, DFT, molecular docking and ADME/T studies

“…Proposed mechanism of 2-hydroxymethyl-18-crown ether-6 catalyzed α-aminophosphonates synthesis.  Due to wide medicinal applications of fluorinated α-aminophosphonates compounds, many studies have reported the interesting biological properties of trifluoromethyl α-aminophosphonates derivatives, which showed the cytotoxic activity toward cancer cells (Kandula et al, 2017;Satish et al, 2018). Herein, we have scrutinized the three synthesized α-aminophosphonates (4p, 4q and 4r) in quantum chemical calculations and modeling molecular study to determine the minimum energy molecular structure and to understand the correlation between the biological activity of α-aminophosphonates and their molecular structures (Cytlak et al, 2017;Turcheniuk et al, 2013).…”

Ionic Liquid Promoted Regio‐Selective Synthesis of 2‐Methyl amino‐3‐Nitro‐pyrano[3,2‐c]chromen‐5‐ones

“…Recently, a biodegradable ionic liquid [(EMIM)Ac] is used as an efficient catalyst for various organic transformation. [35][36][37][38][39] In persistence to our research work on development in synthesis of bioactive heterocycles using green routes, [40][41][42][43][44][45] in this context a three component cyclo-condensation of 4-hydroxy coumarin (1), aromatic-aldehydes 2 (a-v) and (E)-N-Methyl-1-(methylthio)-2-nitro-ethenamine (NMSM) (3) catalyzed by 20 mol % of [(EMIM)Ac] as catalyst in methanol at reflux condition and at solvent free condition at 80 to 85 °C reported (Scheme 1).…”

Facile Synthesis, Spectral (IR, Mass, UV−Vis, NMR), Linear and Nonlinear Investigation of the Novel Phosphonate Compounds: A Combined Experimental and Simulation Study

“…Phosphonate functionalities could be installed chemical skeletons that might bring significant pharmacological activities . Some of the important biological activities of α‐aminophosphonates are antifungal, anti‐inflammatory, antibacterial antioxidant, anticancer, and antiviral etc (See figure ). Beside these, the α‐aminophosphonate compounds act as multidrug resistance reversers with the potential of blocking the NF‐κB pathway as well as cell proliferation .…”