Design, synthesis and biological evaluation of novel nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents

Abstract

A series of 2-Arylamino-3-chloro-1,4-naphthoquinones ( 3), 2-Amino-3-arylsulfanyl-1,4-naphthoquinones ( 5), 2-Arylamino-3-arylsulfanyl-1,4-naphthoquinones ( 6), Dihydrobenzo[ f]naphtho[2,3- b][1,4]thiazepine-6,11-diones ( 9) (via Pictet–Spengler cyclization), Isoindoline-1,3-dione derivatives of 1,4-naphthoquinone ( 13), 2,2′-(1,4-Dioxo-1,4-dihydronaphthalene-2,3-diyl)bis(methylene)dibenzonitrile ( 14), 13-Amino-12-substituted-6 H-benzo[ e]naphtho [2,3- b][1,4]diazepine-6,11(12 H)-diones ( 15– 16), 2-Chloro-3-arylsulfanyl-1,4-naphthoquinones ( 17– 18) and 3-Methyl-6 H-benzo[ b]phenothiazine-6,11(12 H)-dione ( 19) were synthesized and studied for their antifungal and antibacterial activities. The results indicate that compounds 3b, 5a and 5b have potent antifungal activity. Amongst the most promising antifungal compounds, 3b showed better antifungal activity than clinically prevalent antifungal drug Fluconazole (MIC 50 = 2.0 μg/mL) against Sporothrix schenckii (MIC 50 = 1.56 μg/mL), significant profile against Candida albicans (MIC 50 = 1.56 μg/mL), Cryptococcus neoformans (MIC 50 = 0.78 μg/mL) and Trichophyton mentagraphytes (MIC 50 = 1.56 μg/mL) and same antifungal activity when compared with Amphotericin-B against C. neoformans (MIC 50 = 0.78 μg/mL). Compounds 3b, 5a and 5b also showed promising antibacterial activity.