Green Synthesis, antioxidant, and plant growth regulatory Activities of Novel a-furfuryl-2-alkylaminophosphonates

A series of novel α-furfuryl-2-alkylaminophosphonates have been efficiently synthesized from the one-pot threecomponent classical Kabachnik−Fields reaction in a green chemical approach by addition of an in situ generated dialkylphosphite to Schiff’s base of aldehydes and amines by using environmental and eco-friendly silica gel supported iodine as a catalyst by microwave irradiation. The advantage of this protocol is simplicity in experimental procedures and products were resulted in high isolated yields. The synthesized α-furfuryl-2- alkylaminophosphonates were screened to in vitro antioxidant and plant growth regulatory activities and some are found to be potent with antioxidant and plant growth regulatory activities. These in vitro studies have been further supported by ADMET (absorption, distribution, metabolism, excretion, and toxicity), quantitative structure−activity relationship, molecular docking, and bioactivity studies and identified that they were potentially bound to the GLN340 amino acid residue in chain C of 1DNU protein and TYR597 amino acid residue in chain A of 4M7E protein, causing potential exhibition of antioxidant and plant growth regulatory activities. Eventually, title compounds are identified as good blood− brain barrier (BBB)-penetrable compounds and are considered as proficient central nervous system active and neuroprotective antioxidant agents as the neuroprotective property is determined with BBB penetration thresholds

Synthesis and Anti-Pancreatic Cancer Activity Studies of Novel 3-Amino-2-hydroxybenzofused 2-Phospha-γ-lactones

A series of 3-amino-2-hydroxybenzofused 2-phosphalactones (4a-l) has been synthesized from the Kabachnik-Fields reaction via a facile route from a one-pot three-component reaction of diphenylphosphite with various 2-hydroxybenzaldehyes and heterocyclic amines in a new way of expansion. The in vitro anti-cell proliferation studies by MTT assay have revealed them as potential Panc-1, Miapaca-2, and BxPC-3 pancreatic cell growth inhibitors, and the same is supported by molecular docking, QSAR, and ADMET studies. The MTT assay of their SAHA derivatives against the same cell lines evidenced them as potential HDAC inhibitors and identified 4a, 4b, and 4k substituted with 1,3-thiazol, 1,3,4-thiadiazol, and 5-sulfanyl-1,3,4-thiadiazol moieties on phenyl and diethylamino phenyl rings as potential ones. Additionally, the flow cytometric analyses of 4a, 4b, and 4k against BxPC-3 cells revealed compound 4k as a lead compound that arrests the S phase cell cycle growth at low micromolar concentrations. The ADMET properties have ascertained their inherent pharmacokinetic potentiality, and the wholesome results prompted us to report it as the first study on anti-pancreatic cancer activity of cyclic α-aminophosphonates. Ultimately, this study serves as a good contribution to update the existing knowledge on the anticancer organophosphorus heterocyclic compounds and elevates the scope for generation of new anticancer drugs. Further, the studies like QSAR, drug properties, toxicity risks, and bioactivity scores predicted for them have ascertained the synthesized compounds as newer and potential drug candidates. Hence, this study had augmented the array of α-aminophosphonates by adding a new collection of 3-amino-2-hydroxybenzofused 2-phosphalactones, a class of cyclic α-aminophosphonates, to it, which proved them as potential anti-pancreatic cancer agents. ©Mr. R.R.G. and Prof. S.R.C. thank Science and Engineering Research Board (SERB), India for providing financial assistance through a research project grant f.no.: SB/S1/OC-96/2013, Dt: 05-11-2014. Author S.K.B. thanks University Grants Commission (UGC), New Delhi, India for RFSMS (Research Fellowship in Sciences for Meritorious Students) Fellowship (F.4-1/2011, BSR-RFSMS-BSK) under Basic Scientific Research (BSR) Scheme. Authors V.K.R.A. and G.V.Z. are thankful to Ural Federal University for support and acknowledge the financial support of the Ministry of Science and Higher Education of the Russian Federation, Moscow, Russian Federation (grant no.: 075-15-2020-777)