Tiwar, Shailee V.Sharif, Nawaz S.Gajare, Rekha I.Seijas Vázquez, Julio AntonioSangshetti, Jaiprakash N.Damale, Manoj D.Nikalje, Anna Pratima G.2020-05-152020-05-152018Tiwari, S.V.; Sharif, N.S.; Gajare, R.I.; Vazquez, J.A.S.; Sangshetti, J.N.; Damale, M.D.; Nikalje, A.P.G. New 2-Oxoindolin Phosphonates as Novel Agents to Treat Cancer: A Green Synthesis and Molecular Modeling. Molecules 2018, 23, 1981http://hdl.handle.net/10347/22330The work reports the facile synthesis of novel α-aminophosphonate derivatives coupled with indole-2,3-dione moieties, namely the diethyl(substituted phenyl/heteroaryl)(2-(2-oxoindolin-3-ylidene)hydrazinyl)methylphosphonates derivatives 4(a–n). One-pot three component Kabachnik-Fields reactions were used to synthesize these derivatives. The reaction was carried out at room temperature by stirring in presence of ceric ammonium nitrate (CAN) as a green catalyst. The structures of the synthesized compounds were established by spectral studies. The synthesized derivatives 4(a–n) were evaluated for their in vitro anticancer activity against six human cancer cell lines by the SRB assay method. The cancer cell lines used in this research work are SK-MEL-2 (melanoma), MCF-7 (breast cancer), IMR-32 (neuroblastoma) MG-63 (human osteosarcoma), HT-29 (human colon cancer) and Hep-G2 (human hepatoma). All the synthesized derivatives inhibited the cell proliferation. Importantly, all the target compounds showed no cytotoxicity towards normal tissue cells (GI50 > 250 µM). A docking study was performed to predict the mode of action. Docking results indicate that the compounds have good binding with the enzyme tyrosine kinase as well as with microtubules, which makes them dual inhibitors. The result of in-silico bioavailability studies suggests that the compounds from the present series have good oral drug-like properties and are non-toxic in nature. In vivo acute oral toxicity study results indicate that the compounds can be considered safe, and therefore could be developed in the future as good anticancer agents or as leads for the design and synthesis of novel anticancer agentseng© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)http://creativecommons.org/licenses/by/4.0/Indole-2,3-dioneα-aminophosphonatesIn-vitro anticancer activityCeric ammonium nitrateDockingjournal article10.3390/molecules230819811420-3049open access