ABSTRACT
A novel series of enediynes possessing pentafluorophenylsulfoxide have been developed. The innovative compounds possess antiproliferative activity against a broad panel of human cancer cells originating from breast, blood, lung, kidney, colon, prostate, pancreas or skin with IC50 ranging from 0.6 to 3.4⯵M. The antiproliferative activity of enediynes in darkness is associated to their ability to compromise microtubule network. In addition, exposure to UV leads to double-stranded DNA cleavage caused by the newly synthesized molecules reducing further their IC50 in nanomolar range against human tumor cells, including chemo-resistant pancreatic cancer cells. Taken together, the examined data demonstrate that enediynes possessing pentafluorosulfoxide are promising molecules in the cancer therapy.
Subject(s)
Antineoplastic Agents/chemistry , Enediynes/chemistry , Sulfoxides/chemistry , Cell Line, Tumor , DNA/drug effects , DNA Breaks, Double-Stranded/drug effects , DNA Breaks, Double-Stranded/radiation effects , Humans , Microtubules/drug effects , Ultraviolet RaysABSTRACT
The indanyl core is ubiquitous in a large variety of drugs and natural products. Importantly, the ever-increasing demand for chiral catalysts bearing this scaffold calls for state of the art methods allowing for a step-economical enantioselective access to this structural motif. We herein summarize the asymmetric syntheses of indanes with a particular focus on asymmetric catalysis, covering the literature of the last decade until July 2015.
Subject(s)
Indans/chemical synthesis , Organic Chemicals/chemistry , Catalysis , Indans/chemistry , Molecular Conformation , StereoisomerismABSTRACT
An original synthesis of chiral benzofulvenes triggered by organocopper reagents is reported. These enantiopure products are available through a highly chemo-, regio-, diastereo-, and enantioselective bis(alkylating) cycloisomerization process. A double chirality transfer (central-to-axial-to-central) is observed.
