Balakrishna Dulla

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.

Construction and functionalization of fused pyridine ring leading to novel compounds as potential antitubercular agents

A series of fused and functionalized pyridine derivatives were designed, synthesized and tested for their potential antitubercular properties. All these novel compounds were prepared by using multistep methods involving the construction of pyridine ring as a key synthetic step. Some of these compounds were found to be interesting when tested for their antitubercular properties in vitro and one of them appeared as an attractive and potential antitubercular agent.

Sequential C–N and C–O Bond Formation in a Single Pot: Synthesis of 2H-Benzo[b][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 2H-benzo[b][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 2H-benzo[b][1,4]oxazines.

Synthesis and in vitro anti-proliferative effects of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives on various cancer cell lines

A series of 3-(hetero)aryl substituted 3-[(prop-2-ynyloxy)(thiophen-2-yl)methyl]pyridine derivatives were designed as potential anticancer agents. These compounds were conveniently prepared by using Pd/C-Cu mediated Sonogashira type coupling as a key step. Many of these compounds were found to be promising when tested for their in vitro anti-proliferative properties against six cancer cell lines. All these compounds were found to be selective towards the growth inhibition of cancer cells with IC50 values in the range of 0.9-1.7 μM (against MDA-MB 231 and MCF7 cells), comparable to the known anticancer drug doxorubicin.

Pd/C-Mediated Arylation Followed by I2-Catalyzed Hydration Strategy: Preparation of Functionalized Novel Indanone Derivatives

Abstract A simple and inexpensive synthesis of novel 2-(3-oxo-3-arylpropyl)-2,3-dihydro-1H-inden-1-one derivatives has been achieved via Pd/C-mediated arylation followed by I2-mediated regioselective hydration of 2-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-ones. A wide variety of 3-aryl substituted 2-propynyl indanone derivatives were conveniently prepared by using 10% Pd/C-PPh3-CuI as a catalyst system, some of which were used to prepare the corresponding ketones via alkyne hydration in the presence of catalytic I2. In an in vitro study a representative compound showed inhibition of PDE4B (phosphodiesterase type 4B) and binding with this protein in silico GRAPHICAL ABSTRACT

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.