Reactions of 2,3-dichloro-1,4-naphthoquinone with aminophenols: evidence for hydroxy benzophenoxazine intermediate and antibacterial activity

摘要

Reactions of 2,3-dichloro-1,4-naphthoquinone with o/m and p-aminophenols are studied. It was shown that reaction with 2-aminophenol results in 6-chloro-12a-methoxy-7H-benzo[c]phenozaxine-5(12aH)-one (1a) as the major product along with (6-chloro-12a-hydroxy-7H-benzo[c]phenoxazine-5(12aH)-one) (1b) in minor proportions. A major 6-chloro-12a-methoxy-9-methy1-7H-benzo[c]phenoxazin-5(12aH)-one (2a) was isolated from the 4-methyl-2-aminophenol whereas reactions with 3-aminophenol and 4-aminophenol yield products 2-(3-hydroxyphenylamino)-3-chloro-1,4-naphthoquinone (3) and 2-(4hydroxyphenylamino)-3-chloro-1,4-naphthoquinone (4). The hydroxy phenoxazine (1b) was obtained as the minor product which is evident from the single crystal X-ray diffraction studies. Pharmacological potential of these compounds have been evaluated against pathogenic Gram positive and Gram negative bacteria. These derivatives demonstrated broad spectrum of biological activity against all bacterial isolates with the MIC bring in the range of 4-512 mu g/ml. The relatively high MICs were observed compared to the reference antibiotics used. Except lb rest of the other compounds exhibit considerably lower MICs (32-512 mu g/ml), against the two Pseudomonas spp. and relatively high resistance towards reference antibiotics (with the MIC being 1024 mu g/ml). It has been shown that that synergistic action of phenoxazine derivatives in mixing with conventional antibiotics can be explored for treatment of pathogens. (C) 2018 Elsevier B.V. All rights reserved.