Synthesis of Polycyclic Ether-Benzopyrans and In Vitro Inhibitory Activity against Leishmania tarentolae
| Autor: | T. Andrew Mitchell, Marjorie A. Jones, David C. Platt, C. Fiore Apuzzo, Shilpa Pohani, Sarita Singh, Jacob P. Grabowski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Bromides
Acid Phosphatase Pharmaceutical Science Cell Count Drug resistance 010402 general chemistry Ether 01 natural sciences oxabicyclo[3.2.1]-octane Article Catalysis Analytical Chemistry Nitric oxide lcsh:QD241-441 oxidopyrylium Suzuki-Miyaura chemistry.chemical_compound lcsh:Organic chemistry nitric oxide Drug Discovery Benzopyrans Polycyclic Compounds Physical and Theoretical Chemistry cycloaddition Enzyme Assays Infectivity benzopyran Leishmania Cycloaddition Reaction biology 010405 organic chemistry Organic Chemistry Acid phosphatase biology.organism_classification secreted acid phosphatase In vitro 0104 chemical sciences Benzopyran chemistry Biochemistry Chemistry (miscellaneous) biology.protein Molecular Medicine Neuroglia Palladium Boronic acid |
| Zdroj: | Molecules Volume 25 Issue 22 Molecules, Vol 25, Iss 5461, p 5461 (2020) |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules25225461 |
| Popis: | Construction of a focused library of polycyclic ether-benzopyrans was undertaken in order to discover new therapeutic compounds that affect Leishmania growth and infectivity. This is especially of interest since there are few drug therapies for leishmaniasis that do not have serious drawbacks such high cost, side effects, and emerging drug resistance. The construction of these polycyclic ether-benzopyrans utilized an acetoxypyranone-alkene [5+2] cycloaddition and the Suzuki-Miyaura cross-coupling. The multi-gram quantity of the requisite aryl bromide was obtained followed by effective Pd-catalyzed coupling with boronic acid derivatives. Compounds were tested in vitro using the parasitic protozoan, Leishmania tarentolae. Effects of concentration, time, and exposure to light were evaluated. In addition, the effects on secreted acid phosphatase activity and nitric oxide production were investigated, since both have been implicated in parasite infectivity. The data presented herein are indicative of disruption of the Leishmania tarentolae and thus provide impetus for the development and testing of a more extensive library. |
| Databáze: | OpenAIRE |
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