Synthesis and evaluation of 3-amino/guanidine substituted phenyl oxazoles as a novel class of LSD1 inhibitors with anti-proliferative properties

A series of functionalized phenyl oxazole derivatives was designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells, and in vivo for effects using zebrafish embryos. These compounds are likely to act via multiple epigenetic mechanisms specific to cancer cells including LSD1 inhibition

Synthesis and pharmacological characterization of novel N & O containing heterocyclic compounds as potential therapeutic agents

The majority of pharmaceuticals and biologically active agrochemicals are heterocyclic compounds; it represents their immense importance in serving mankind. The purpose of this thesis was to investigate feasibility of making potential biological active noval heterocyclic compounds designed based on lead molecules. The work accomplished in this thesis includes five different chapters to explain importance, achieve simple and fused-ring heteropolicyclic systems having potential pharmacological properties. The first chapter briefly explains importance of heterocyclic compounds and research objective. The second chapter of thesis concerns with target-oriented synthesis to access complex dehydro shikimate analogues containing a pyridine/isoquinoline unit with antitubercular activities with MIC: 4-10μM. Third chapter deals with study of novel synthetic approach to the one pot synthesis of 2H-benzo[b] [1,4]oxazines with anti inflammatory activites. In the fourth chapter is presented as a series of functionalized phenyl oxazole derivatives were designed, synthesized and screened in vitro for their activities against LSD1 and for effects on viability of cervical and breast cancer cells (IC50: 1-10 nM), and in vivo for effects using zebrafish embryos. Indeed it also explains the designing and cost effective route to synthesis of LSD1 inhibitors. Finally, fifth one is related to the intramolecular 1,3-dipolar cycloaddition of isovanillin derived N-aryl hydroxylamines possessing ortho-allylic dipolarophiles affords novel benzo analogues of tricyclic isoxazolidines that can be readily transformed into functionalized lactams, γ-aminoalcohols and oxazepines. The corresponding N-unsubstituted hydroxylamines give rise to tetrahydroisoquinolines. Anxiogenic properties of these compounds were tested in zebrafish. Moreover, in all chapters in silico docking studies were performed to predict binding interactions of the most potent scaffolds synthesized and reported inhibitors with the selected targets. At the end of each chapter are drawn a series of conclusions, concerning the investigations performed and the results obtained

Sequential C–N and C–O Bond Formation in a Single Pot: Synthesis of 2<i>H</i>-Benzo[<i>b</i>][1,4]oxazines from 2,5-Dihydroxybenzaldehyde and Amino acid Precursors

Functionalized β-aryl alanine ester derivatives were found to undergo rapid C–N and C–O bond formation with quinol carbonyl compounds to afford 2<i>H</i>-benzo[<i>b</i>][1,4]oxazines in good to excellent yields. This unprecedented finding reported herein offers a straightforward, highly efficient, and rapid method for the synthesis of 2<i>H</i>-benzo[<i>b</i>][1,4]oxazines

Sequential C–N and C–O Bond Formation in a Single Pot: Synthesis of 2<i>H</i>-Benzo[<i>b</i>][1,4]oxazines from 2,5-Dihydroxybenzaldehyde and Amino acid Precursors

Functionalized β-aryl alanine ester derivatives were found to undergo rapid C–N and C–O bond formation with quinol carbonyl compounds to afford 2<i>H</i>-benzo[<i>b</i>][1,4]oxazines in good to excellent yields. This unprecedented finding reported herein offers a straightforward, highly efficient, and rapid method for the synthesis of 2<i>H</i>-benzo[<i>b</i>][1,4]oxazines

Organic Nanovesicular Cargoes for Sustained Drug Delivery: Synthesis, Vesicle Formation, Controlling “Pearling” States, and Terfenadine Loading/Release Studies

“Sustained drug delivery systems” which are designed to accomplish long-lasting therapeutic effect are one of the challenging topics in the area of nanomedicine. We developed an innovative strategy to prepare nontoxic and polymer stabilized organic nanovesicles (diameter: 200 nm) from a novel bolaamphiphile, where two hydrogen bonding acetyl cytosine molecules connected to 4,4′′-positions of the 2,6-bispyrazolylpyridine through two flexible octyne chains. The nanovesicles behave like biological membrane by spontaneously self-assembling into “pearl-like” chains and subsequently forming long nanotubes (diameter: 150 nm), which further develop into various types of network-junctions through self-organization. For drug loading and delivery applications, the nanovesicles were externally protected with biocompatible poly(ethyleneglycol)-2000 to prevent them from fusion and ensuing tube formation. Nontoxic nature of the nanovesicles was demonstrated by zebrafish teratogenicity assay. Biocompatible nanovesicles were loaded with “terfenadine” drug and successfully utilized to transport and release drug in sustained manner (up to 72 h) in zebrafish larvae, which is recognized as an emerging in vivo model system