Author:

Keywords:

Science & Technology, Physical Sciences, Chemistry, Multidisciplinary, Chemistry, HUMAN-IMMUNODEFICIENCY-VIRUS, ISATIN DERIVATIVES, MANNICH-BASES, IN-VITRO, REVERSE-TRANSCRIPTASE, INHIBITORS, ANTIFUNGAL, ANTIBACTERIAL, SCHIFF, DESIGN, 03 Chemical Sciences, 34 Chemical sciences

Abstract:

© The Royal Society of Chemistry 2015. Suzuki-Miyaura reactions of 4,7-dichloro-N-methylisatin provide a convenient access to arylated methylisatins. The reactions proceed with excellent site-selectivity in favour of position 4, due to electronic reasons. All the new compounds were evaluated in vitro for their antiviral activity against the replication of HIV-1 and HIV-2 in MT4 cells using a MTT assay. 4-(4-Acetylphenyl)-7-chloro-1-methylindoline-2,3-dione (8l), containing an acetyl group located at carbon C(4) of the isatin backbone, showed an IC50value of >3.47 μM against HIV-2 with a therapeutic index (SI) of 4. This means that 8l was cytotoxic to MT-4 cells at a CC50value of 13.43 μM; also 4,7-dichloro-1-methylindoline-2,3-dione (5), 7-chloro-4-(4-chlorophenyl)-1-methylindoline-2,3-dione (8c), 7-chloro-4-(4-ethoxyphenyl)-1-methylindoline-2,3-dione (8g) and 7-chloro-1-methyl-4-(4-vinylphenyl)indoline-2,3-dione (8m) were cytotoxic to MT-4 cells within a 2.21-3.11 μM concentration range. In a docking study, 8l interacted with several amino acids in the reverse transcriptase (RT) binding site of HIV-2.