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
BACKGROUND: Despite the need to develop new herbicides with different modes of action, due to weed resistance, many important classes of compounds have been studied poorly for this purpose. Benzoxazoles are considered privileged structures because of their biological activities, but their phytotoxic activities have not received a lot of attention until now. RESULTS: Double vinylic substitution reactions were carried out to furnish four 2-nitromethylbenzoxazoles and one oxazolidine. Benzoxazol-2-ylmethanamine was obtained by reduction of compound 3a. These compounds were evaluated for their phytotoxicity in Allium cepa (onion), Solanum lycopersicum (tomato), Cucumis sativus (cucumber) and Sorghum bicolor (sorghum). Comparison with oxazolidine analogue allowed us to understand that the benzoxazolic structure is very important for the herbicidal activity. CONCLUSION: All the synthesized compounds exhibited biological activity on seed germination. The four 2-nitromethylbenzoxazoles showed phytotoxic activity and the 5-chloro-2-(nitromethyl)benzo[d]oxazole (3b) exhibited higher inhibition than the commercial herbicide against all four plant species tested. © 2018 Society of Chemical Industry.
Subject(s)
Benzoxazoles/pharmacology , Cucumis sativus/drug effects , Herbicides/pharmacology , Onions/drug effects , Solanum lycopersicum/drug effects , Sorghum/drug effects , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Aedes/drug effects , Insecticides/pharmacology , Phenols/pharmacology , Animals , Insecticides/chemical synthesis , Insecticides/toxicity , Larva/drug effects , Lethal Dose 50 , Phenols/chemistry , Phenols/isolation & purification , Phenols/toxicity , Time FactorsABSTRACT
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.
Subject(s)
Animals , Phenols/pharmacology , Aedes/drug effects , Insecticides/pharmacology , Phenols/isolation & purification , Phenols/toxicity , Phenols/chemistry , Time Factors , Insecticides/chemical synthesis , Insecticides/toxicity , Larva/drug effects , Lethal Dose 50ABSTRACT
Selective Estrogen Receptor Modulators (SERMs) are characteristically capable of being antagonist and agonist of estrogen receptors and, therefore, they can inhibit or stimulate estrogen production in different tissues. Aiming to contribute to the identification of new synthetic SERMs candidates, the basic skeletons of raloxifene and tamoxifene were used as model. Here of, a set of 2,3-diaryl-quinoxalines having 2-(piperidin-1- yl)ethanol in the side chain have been synthesized and evaluated against human mammary carcinoma cells estrogen dependent (MCF-7), as well as in recombinant yeast assays (RYA) expressing estrogen receptor. Compound LSPN332 showed 40% inhibition of MCF-7 and EC50=290.6 µM in RYA. The efficient synthesis of 2,3-diarylquinoxalines represents an excellent opportunity to identify new SERMs, and should therefore be of interest to the medicinal chemistry community.
