C. Suresh Reddy

PEG-SO3H 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-Fields 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 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.

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.

Phosphomolybdic Acid/SiO2 as Heterogeneous Solid Acid Catalyst for the Rapid Synthesis of N-Substituted Pyrroles

Abstract Isatins react efficiently with 4-hydroxyproline in the presence of 10 mol% of PMA/SiO2 in acetonitrile/water (4:1) under reflux conditions to furnish N-substituted pyrroles in excellent yields. Similarly, 11H-indeno[1,2-b]quinoxalin-11-ones also participated in this reaction.

Tween-20: An Efficient Catalyst for One-Pot Synthesis of α-Aminophosphonates in Aqueous Media

Abstract A green one-pot three-component synthesis has been developed for α-aminophosphonates by condensation of aldehydes, amines, and diethylphosphite by using nonionic surfactant Tween-20 as catalyst in aqueous media. The results showed that this synthetic route for α-aminophosphonates takes just 25–60 min for completion at 60 °C and affords 64%–91% yields depending on the nature of the amine substrates. The major advantages of this novel method are green reaction conditions with water as solvent, simple workup, less reaction times, and high to moderate yields. GRAPHICAL ABSTRACT

Synthesis, Antimicrobial, and Antioxidant Activity of New α-Aminophosphonates

Abstract A new class of α-aminophosphonates 2–16 has been synthesized by the reaction of equimolar quantities of Schiffs bases with diethyl/dimethyl/diphenyl phosphite in dry toluene under reflux conditions using tetramethylguanidine (TMG) as a catalyst via Pudovik reaction in high yields (78–89%). The structures of the title compounds have been established by elemental; infrared (IR); 1H-, 13C-, and 31P-NMR; and mass spectral data analyses. They were found to possess significant antimicrobial and antioxidant activity. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT

Green Synthesis of Aminobisphosphonates Under Microwave Irradiation

Abstract A simple, efficient, and environmentally benign green chemical method has been developed for the synthesis of aminobisphosphonates by reacting aliphatic/aromatic 2°-amines, dimethylphosphite, and triethylorthoformate by microwave irradiation under solvent-free conditions, in the presence of an alumina solid support. The advantages of this method are less reaction time, simple work-up, and excellent yields. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file. GRAPHICAL ABSTRACT

Polyethylene Glycol–Promoted Dialkyl, Aryl/Heteroaryl Phosphonates

Abstract A new, straightforward polyethylene glycol–promoted method for Michaelis–Arbuzov rearrangement has been described.

Silica-Supported Tungstic Acid Catalyzed Synthesis and Antioxidant Activity of α-Hydroxyphosphonates

GRAPHICAL ABSTRACT Abstract A green and efficient method has been accomplished for the synthesis of α-hydroxyphosphonates using silica-supported tungstic acid (STA) as a heterogeneous catalyst under solvent-free conditions at ambient temperature. The compounds obtained were characterized by spectral and analytical studies and screened in vitro for the antioxidant activity by four methods viz., DPPH free radical scavenging assay, hydrogen peroxide scavenging assay, NO method, FRAP method. The results indicated that the title compounds are potential antioxidants and are comparable to the antioxidant property of the standard ascorbic acid.

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.