biostudies-literatureUnknown14(33)Nagavath RWe present, for the first time, the organo-<i>N</i>-heterocyclic carbene (NHC) catalyzed 1,3-dipolar cycloaddition of 4β-<i>O</i>-propargyl podophyllotoxin (1) with <i>in situ</i> aromatic nitrile oxides to afford regioselective 4β-isoxazolepodophyllotoxin hybrids (6a-n) in benign aqueous-organic media. Preliminary anticancer activity results showed that compound 6e displayed superior activity against MCF-7, HeLa and MIA PaCa2 human cell lines compared with podophyllotoxin. Compounds 6j and 6n showed greater activity against the MCF-7 cell line than the positive control. Caspase activation studies revealed that compound 6e at 20 μg ml^-1 concentration had greater caspase 3/7 activation in MCF-7 and MIAPaCa2 cells than podophyllotoxin. Furthermore, <i>in vitro</i> tubulin polymerization inhibition studies revealed that compound 6e showed comparable activity with podophyllotoxin. Finally, <i>in silico</i> molecular docking studies of compounds 6e, 6j, 6n and podophyllotoxin on α,β-tubulin (pdb id 1SA0) revealed that compound 6n showed excellent binding energies and inhibition constants compared with podophyllotoxin.RSC advances23574-23582https://www.ebi.ac.uk/biostudies/studies/S-EPMC11276401biostudies-literatureOrgano NHC catalyzed aqueous synthesis of 4β-isoxazole-podophyllotoxins: <i>in vitro</i> anticancer, caspase activation, tubulin polymerization inhibition and molecular docking studies.PMC11276401Nagavath RThupurani MKBadithapuram VManchal RVasam CSThirukovela NSfalseOrgano NHC catalyzed aqueous synthesis of 4β-isoxazole-podophyllotoxins: <i>in vitro</i> anticancer, caspase activation, tubulin polymerization inhibition and molecular docking studies.We present, for the first time, the organo-<i>N</i>-heterocyclic carbene (NHC) catalyzed 1,3-dipolar cycloaddition of 4β-<i>O</i>-propargyl podophyllotoxin (1) with <i>in situ</i> aromatic nitrile oxides to afford regioselective 4β-isoxazolepodophyllotoxin hybrids (6a-n) in benign aqueous-organic media. Preliminary anticancer activity results showed that compound 6e displayed superior activity against MCF-7, HeLa and MIA PaCa2 human cell lines compared with podophyllotoxin. Compounds 6j and 6n showed greater activity against the MCF-7 cell line than the positive control. Caspase activation studies revealed that compound 6e at 20 μg ml^-1 concentration had greater caspase 3/7 activation in MCF-7 and MIAPaCa2 cells than podophyllotoxin. Furthermore, <i>in vitro</i> tubulin polymerization inhibition studies revealed that compound 6e showed comparable activity with podophyllotoxin. Finally, <i>in silico</i> molecular docking studies of compounds 6e, 6j, 6n and podophyllotoxin on α,β-tubulin (pdb id 1SA0) revealed that compound 6n showed excellent binding energies and inhibition constants compared with podophyllotoxin.2024-01-01T00:00:00Z2024 Jul2026-06-02T23:12:11.484Z2025-04-19T13:11:24.298ZS-EPMC112764013907024910.1039/d4ra04297b