Synthesis and biological evaluation of cinnamido linked benzophenone hybrids as tubulin polymerization inhibitors and apoptosis inducing agents.

A new class of hybrid molecules containing cinnamide subunit linked to benzophenone as inhibitors of tubulin polymerization were synthesized and evaluated for their anticancer potential. These hybrids exhibit anticancer activity with IC50 values ranging from 0.06 to 16.3µM. Compounds 4f and 4g possessing fluoro and trifluoromethyl on the cinnamido subunit showed significant cytotoxic activity with IC50 values 0.06 and 0.09µM against HeLa cell line, respectively. These compounds showed cell cycle arrest at G2/M phase of the cell cycle and inhibited tubulin polymerization followed by activation of caspase-3 activity and apoptotic cell death. Further in vitro tubulin polymerization assay showed that the level of tubulin inhibition was comparable to that of 2a for the compounds 4f and 4g. Moreover, Hoechst 33258 staining and DNA fragmentation assay suggested that these compounds induce cell death by apoptosis. Overall, the current study demonstrates that the synthesis of benzophenone linked cinnamide subunit conjugates as promising anticancer agents with G2/M arrest and apoptotic-inducing ability via targeting tubulin.

Synthesis and biological evaluation of benzo[b]furans as inhibitors of tubulin polymerization and inducers of apoptosis.

A series of benzo[b]furans was synthesized with modification at the 5-position of the benzene ring by introducing C-linked substituents (aryl, alkenyl, alkynyl, etc.). These compounds were evaluated for their antiproliferative activities, inhibition of tubulin polymerization, and cell-cycle effects. Some compounds in this series displayed excellent activity in the nanomolar range against lung cancer (A549) and renal cell carcinoma (ACHN) cancer cell lines. (6-Methoxy-5-((4-methoxyphenyl)ethynyl)-3-methylbenzofuran-2-yl)(3,4,5-trimethoxyphenyl)methanone (26) and (E)-3-(6-methoxy-3-methyl-2-(1-(3,4,5-trimethoxyphenyl)vinyl)benzofuran-5-yl)prop-2-en-1-ol (36) showed significant activity in the A549 cell line, with IC50 values of 0.08 and 0.06 µM, respectively. G2/M cell-cycle arrest and subsequent apoptosis was observed in the A549 cell line after treatment with these compounds. The most active compound in this series, 36, also inhibited tubulin polymerization with a value similar to that of combretastatin A-4 (1.95 and 1.86 µM, respectively). Furthermore, detailed biological studies such as Hoechst 33258 staining, DNA fragmentation and caspase-3 assays, and western blot analyses with the pro-apoptotic protein Bax and the anti-apoptotic protein Bcl-2 also suggested that these compounds induce cell death by apoptosis. Molecular docking studies indicated that compound 36 interacts and binds efficiently with the tubulin protein.

PEG-SO(3)H catalyzed synthesis and cytotoxicity of α-aminophosphonates.

One pot three-component PEG-SO(3)H catalyzed reaction of 4-(Pyridin-4-yl)benzaldehyde and triethyl phosphite with various primary amines afforded α-aminophosphonates with high yields by the Kabachnik-Field's reaction. These new structurally diversified set of α-aminophosphonates (4a-j) were evaluated for their anti-tumor activity on human chronic myeloid leukemia cells (K 562), human colon carcinoma cells (Colo 205) along with non-cancerous human embryonic kidney cells (HEK 293). They showed moderate activity on both cancerous cells and non-cancerous cells.

Synthesis and bio-activity evaluation of tetraphenyl(phenylamino) methylene bisphosphonates as antioxidant agents and as potent inhibitors of osteoclasts in vitro.

A new series of tetraphenyl bisphosphonates have been elegantly synthesized by one-pot method and were characterized by elemental analysis, FTIR, 1H, 13C, 31P NMR, mass spectra and evaluated for their in vitro antibone resorptive activity by inhibiting growth of osteoclasts. Two bisphosphonates 3g and 3f showed marked inhibition ratio (8 µM and 10 µM) and emerged as lead compounds. All compounds were tested for their antioxidant (DPPH scavenging, reducing power and inhibition of lipid peroxidation). They exhibited potent in vitro antioxidant activity dose-dependently.