Synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents

Figures & data

Figure 1. The biosynthesis of chitin.

Figure 2. Some reported antimicrobial agents containing coumarin moiety.

Figure 3. The structures of polyoxin B, Nikkomycin Z and designed compounds.

Scheme 1. Synthesis of compounds 6a–t. Reagents and conditions: (a) SOCl₂, EtOH, rt, 12 h. (b) CH₃C(OCH₃)₂CH₃, p-TsOH, benzene, 80 °C; dioxine, H₂O, NaOH. (c) SOCl₂, CHCl₃, 40–50 °C, 4 h. (d) xylol, p-TsOH, 145 °C. (e) DCC, HOBt, DMAP, CH₂Cl₂. (f) DCC, HOBt, DMAP, CH₂Cl₂;50%CF₃COOH, 35 °C.

Table 1. The MIC values (μg/mL) of compounds 6a–t against fungi in vitro.

Compound	R1	R2	Yield (%)	Candida albicans	Aspergillus flavus	Aspergillums fumigates	Cryptococcus neoformans
6a	F	H	20	64	128	128	256
6b	Cl	H	15	32	64	64	4
6c	Br	H	34	32	64	64	32
6d	CH3	H	19	64	32	128	64
6e	OCH3	H	15	256	64	128	256
6f	F	CH3	15	512	512	128	512
6g	Cl	CH3	11	64	256	128	256
6h	Br	CH3	33	32	128	128	64
6i	CH3	CH3	21	64	64	128	128
6j	OCH3	CH3	25	128	128	128	256
6k	F	OH	30	32	64	128	64
6l	Cl	OH	35	256	256	256	256
6m	Br	OH	40	64	128	64	128
10n	CH3	OH	33	64	32	64	16
6o	OCH3	OH	26	32	64	16	32
6p	F	Cl	41	256	512	256	512
6q	Cl	Cl	29	128	128	128	256
6r	Br	Cl	15	32	64	64	64
10s	CH3	Cl	21	128	256	256	256
10t	OCH3	Cl	18	128	128	256	128
Fluconazole	–	–	–	16	64	32	8
Polyoxin B	–	–	–	32	64	64	16

Figure 4. The inhibition ratio of compounds at 300 μg/mL.

Figure 5. The IC₅₀ values of the some compounds against CHS.