ABSTRACT
N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity. In silico predictions indicate that the two most active derivatives exhibit physicochemical properties within the range of drug-like compounds and showed potential to interact with HDAC8 and ERK1 cancer-related targets.
Subject(s)
Antineoplastic Agents , Ethylenes , Heterocyclic Compounds , Ketones , Humans , Cell Line, Tumor , Ethylenes/chemistry , Ethylenes/pharmacology , Heterocyclic Compounds/chemistry , Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Ketones/chemistry , Ketones/pharmacology , Ketones/chemical synthesis , Structure-Activity Relationship , Histone Deacetylases/metabolism , Molecular Docking Simulation , Drug Screening Assays, Antitumor , Acetals/chemistry , Acetals/pharmacology , Acetals/chemical synthesis , Repressor ProteinsABSTRACT
ABSTRACT Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins. These derivatives were tested for toxicity against Aedes aegypti larvae. The results showed that iodohydrins are very promising compounds for making commercial products to combat the vector mosquito larvae presenting a LC50 of 0.0023 ppm after 72 h of exposure.