Illuminating Dark Chemical Matter Using the Cell Painting Assay.

Screening for small-molecule modulators of disease-relevant targets and phenotypes is the first step on the way to new drugs. Large compound libraries have been synthesized by academia and, particularly, pharmaceutical companies to meet the need for novel chemical entities that are as diverse as possible. Screening of these compound libraries revealed a portion of small molecules that is inactive in more than 100 different assays and was therefore termed "dark chemical matter" (DCM).

A divergent intermediate strategy yields biologically diverse pseudo-natural products.

The efficient exploration of biologically relevant chemical space is essential for the discovery of bioactive compounds. A molecular design principle that possesses both biological relevance and structural diversity may more efficiently lead to compound collections that are enriched in diverse bioactivities. Here the diverse pseudo-natural product (PNP) strategy, which combines the biological relevance of the PNP concept with synthetic diversification strategies from diversity-oriented synthesis, is reported.

A highly enantioselective intramolecular 1,3-dipolar cycloaddition yields novel pseudo-natural product inhibitors of the Hedgehog signalling pathway.

combination of natural product (NP) fragments by means of efficient, complexity- and stereogenic character-generating transformations to yield pseudo-natural products (PNPs) may explore novel biologically relevant chemical space. Pyrrolidine- and tetrahydroquinoline fragments rarely occur in combination in nature, such that PNPs that embody both fragments might represent novel NP-inspired chemical matter endowed with bioactivity. We describe the synthesis of pyrrolo[3,2-]quinolines by means of a highly enantioselective intramolecular -1,3-dipolar cycloaddition catalysed by the AgOAc/()-DMBiphep complex.

Unprecedented Combination of Polyketide Natural Product Fragments Identifies the New Hedgehog Signaling Pathway Inhibitor Grismonone.

Pseudo-natural products (pseudo-NPs) are de novo combinations of natural product (NP) fragments that define novel bioactive chemotypes. For their discovery, new design principles are being sought. Previously, pseudo-NPs were synthesized by the combination of fragments originating from biosynthetically unrelated NPs to guarantee structural novelty and novel bioactivity.

Spatial targeting of Bcl-2 on endoplasmic reticulum and mitochondria in cancer cells by lipid nanoparticles.

The presence of the same proteins at different sub-cellular locations with completely different functions adds to the complexity of signalling pathways in cancer. Subsequently, it becomes indispensable to understand the diverse critical roles of these proteins based on their spatial distribution for the development of improved cancer therapeutics. To address this, in this work, we report the development of endoplasmic reticulum (ER) and mitochondria targeted nanoscale particles to spatially impair anti-apoptotic Bcl-2 protein in these organelles in HeLa cervical cancer cells.

Mitochondrial Impairment by Cyanine-Based Small Molecules Induces Apoptosis in Cancer Cells.

Mitochondrion, the powerhouse of the cells, has emerged as one of the unorthodox targets in anticancer therapy due to its involvement in several cellular functions. However, the development of small molecules for selective mitochondrial damage in cancer cells remained limited and less explored. To address this, in our work, we have synthesized a natural product inspired cyanine-based 3-methoxy pyrrole small molecule library by a concise strategy.

Hydrazide-Hydrazone Small Molecules as AIEgens: Illuminating Mitochondria in Cancer Cells.

Aggregation-induced-emission luminogens (AIEgens) have gained considerable attention as interesting tools for several biomedical applications, especially for bioimaging due to their brightness and photostability. Numerous AIEgens have been developed for lighting up the subcellular organelles to understand their forms and functions not only healthy but also unhealthy states, such as in cancer cells. However, there is lack of easily synthesizable, biocompatible small molecules for illuminating mitochondria (powerhouses) inside cells.

Impairing Powerhouse in Colon Cancer Cells by Hydrazide-Hydrazone-Based Small Molecule.

Mitochondrion has emerged as one of the unconventional targets in next-generation cancer therapy. Hence, small molecules targeting mitochondria in cancer cells have immense potential in the next-generation anticancer therapeutics. In this report, we have synthesized a library of hydrazide-hydrazone-based small molecules and identified a novel compound that induces mitochondrial outer membrane permeabilization by inhibiting antiapoptotic B-cell CLL/lymphoma 2 (Bcl-2) family proteins followed by sequestration of proapoptotic cytochrome .

Iron-Catalyzed Batch/Continuous Flow C-H Functionalization Module for the Synthesis of Anticancer Peroxides.

Iron-catalyzed dehydrogenative cross-coupling of carbonyl compounds with aliphatic peroxide was developed under mild conditions. A library of linear alkylated and arylated peroxides are synthesized in good to excellent yield. This method is highly selective and general for a range of biologically important derivatives of 2-oxindole, barbituric acid, and 4-hydroxy coumarin with a good functional group tolerance and without the cleavage of the peroxide bond.

Biological Activity of Coumarin Derivatives as Anti-Leishmanial Agents.

Cutaneous leishmaniasis affects nearly 0.7 to 1.3 million people annually.

Synthesis, characterization and in vitro evaluation of novel vitamin D3 nanoparticles as a versatile platform for drug delivery in cancer therapy.

Development of novel nanotechnology based platforms can impact cancer therapeutics in a paradigm shifting manner. The major concerns in drug delivery in cancer therapy are the biocompatibility, biodegradability, non-toxic nature, easy and short synthesis and versatility of the nanovectors. Herein we report the engineering of versatile nanoparticles from biocompatible, biodegradable and non-toxic lipid soluble vitamin D3.