Investigation of some diethyl (4-(dimethylamino)-2,5-dihydro-2,5-dioxo-1-phenyl-1H-pyrrol-3-yl)(hydroxy)methylphosphonate derivatives for In silico pharmacokinetic profile and In vitro anticancer activity

Maleimide is an important pharmacophore having several biological activities. Maleimide derivatives linked with hydroxy phosphonate moiety had been investigated for their antimicrobial activity. As an extension to the previous work, we could perform in silico screening of the pharmacokinetic profile and in vitro anticancer activity determination of these compounds. In silico pharmacokinetic (ADMET) profiles were explored. Further, in vitro anticancer activities were carried out on MDA-MB-231, MCF-7, and A-549 cell lines to propose a possible role of these derivatives in the treatment of cancer. All the molecules ( 5a-5g ) exhibited desired physicochemical properties needed for oral bioavailability. All the synthesized molecules exhibited high GI absorption which is the most needed property for drug development. In acute toxicity predictions, all the molecules fall under toxicity class IV. All synthesized molecules showed a preference for cell growth inhibition against breast (MDA-MB-231 and MCF-7) and lung (A-549) cancer cell lines. Amongst all the molecules, 5d exhibited most potent activity (GI 50 (μM)] against MDA-MB-231 (13.66 ± 0.038), A-549 (13.62 ± 0.041), MCF-7 (10.81 ± 0.038) which possess trifluoro substitution at meta-position. From present investigation, we report compound 5d [diethyl (4-(dimethylamino)-1-(3-(trifluoromethyl)phenyl)-2,5-dihydro-2,5-dioxo-1 H -pyrrol-3-yl)-(hydroxy)methylphosphonate] as promising anti-breast and lung-cancer agent. The cellular toxicity of the novel compounds was also evaluated using normal mouse embryonic fibroblast (NIH/3T3) cell lines. From this study, maleimide linked with hydroxy phosphonate can be treated as a lead nucleus for further development of novel anticancer agents using different in vitro and in vivo models. Graphical abstract