Fe3 O4 nanoparticles mediated synthesis of novel spirooxindole-dihydropyrimidinone molecules as Hsp90 inhibitors.

Heat shock protein 90 (Hsp90) is a validated molecular chaperone considered as the new key recipient for cancer intervention. The current study illustrates the synthesis of novel spirooxindole-dihydropyrimidinones (4a-j) by Fe3 O4 nanoparticles intervened synthesis and their Hsp90 ATPase inhibitory activity was investigated by the malachite green assay. All the compounds in the study demonstrated a moderate to potent ATPase inhibitory profile, with IC50 values ranging from 0.18 to 6.80 µM. Compounds 4j, 4h, 4f, and 4i exhibited maximum inhibitory potential with IC50 values of 0.18, 0.20, 0.35, and 0.55 µM, respectively. They were found to be better than the standard drug, geldanamycin (Hsp9 ATPase inhibition IC50 = 0.90 µM). Compounds 4h and 4j with IC50 values of 22.82 ± 0.532, 20.78 ± 0.234 and 21.32 ± 0.765, 28.43 ± 0.653 µM showed significantly greater potencies against the MCF-7 and HepG2 cell lines, respectively. Compound 4j showed good antioxidant activities in the DPPH test and H2 O2 assay (IC50 = 20.13.23 ± 0.32 and 23.27 ± 0.32 µg/mL) when compared with the standard ascorbic acid (IC50 = 19.16 ± 0.20 and 20.66 ± 1.09 µg/mL). A molecular docking study was performed to observe the binding efficiency and steric interactions of the lead moiety.

Fe3O4 Nanoparticles Mediated Synthesis of Novel Isatin-dihydropyrimidinone Hybrid Molecules as Antioxidant and Cytotoxic Agents.

BACKGROUND: The present study emphasizes on designing a new series of isatin-dihydropyrimidinone derivatives by adopting a hybrid pharmacophore approach. Fe3O4 nanoparticles (Fe3O4 NP) are magnetically recoverable and are effective catalysts adequately used to synthesize Isatin-dihydropyrimidinones. Individual derivatives of Isatin and dihydropyrimidinone are equipotent to treat cytotoxicity. OBJECTIVE: The present work was planned to fuse two pharmacophores (Isatin, dihydropyrimidinone) and to examine any synergistic effect in the anticancer activity. METHOD: The individual compounds are synthesized by adopting appropriate synthetic routes like sandmayers and biginellis reaction and are fused together by using glacial acetic acid and Methanolic KOH to form novel Isatindihydropyrimidinone hybrids. All the new series of hybrids 7a-l were characterized by FT-IR, 1H NMR, 13C NMR, elemental analysis and Mass spectroscopy. The antioxidant activity of the synthesized compounds was assessed by using two models: 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) and Hydrogen peroxide (H2O2) scavenging assay. RESULTS: From the results it can be inferred that nearly all the synthesized compounds have shown antioxidant activity at the tested dose as correlated with the standard ascorbic acid. The in vitro cytotoxic activity was assayed by using MTT assay. Compound 7l with IC50 values 22.13, 25.68 and 35.59 µM has significantly greater potency against MCF- 7, HeLa and IMR-32 cell lines. CONCLUSION: The compounds with halogen and electron withdrawing groups at the C-5 position of isatin ring exhibited significant antioxidant and cytotoxic activity.

Hydrazones as a privileged structural linker in antitubercular agents: a review.

Hydrazones are a versatile linker of connecting various classes of organic compounds with a unique structural feature of hydrogen bonding donor and the hydrogen bonding acceptor region. An extensive number of research has been carried out on hydrazone derivatives as a potent class of antitubercular agents. The present review focuses on the chemistry, antitubercular activity and structure activity relationship (SAR) of diverse classes of phenyl and heterocyclic based hydrazones.

Liquid chromatography-tandem mass spectrometric assay for eltrombopag in 50µL of human plasma: a pharmacokinetic study.

Eltrombopag is a thrombopoietin receptor agonist, used in the treatment of thrombocytopenia. This paper describes a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay method for the determination of eltrombopag in human plasma samples using eltrombopag 13C4 as internal standard (IS). Analyte and the IS were extracted from 50µL of human plasma using protein precipitation technique with no drying, evaporation and reconstitution steps. The chromatographic separation was achieved on a C18 column by using a mixture of 10mM ammonium formate (pH3) and acetonitrile (10:90, v/v) as the mobile phase at a flow rate of 1.0mL/min. The linearity of the method was established in the concentration range 50.0-10007ng/mL with r(2)≥0.99. The intra-day and inter-day precision and accuracy results in four validation batches across five concentration levels were well within the acceptance limits. The proposed method was found to be applicable to pharmacokinetic studies.