Synthesis and characterization of some hydroxypyridone derivatives and their evaluation as antimicrobial agents

Figures & data

Scheme 1.  Reagents and reaction conditions: (i) ethanol, NH₂NH₂·H₂O, ref lux, 1 h; (ii) arylsulfonyl chloride, pyridine, ref lux, 4 h; (iii) anhyd. K₂CO₃, dry acetone, RNCO, ref lux, 18 h; (iv) anhyd. K₂CO₃, dry acetone, RNCS, ref lux, 10 h; (v) ethyl bromoacetate, Na acetate, ethanol, ref lux 2 h; (vi) ethanol, phenacyl bromide, Na acetate, ref lux 2 h; (vii) approp. aldehyde, ref lux, 3 h; (viii) thioacetic acid, dry dioxan, ref lux 12 h.

Scheme 2.  Reagents and reaction conditions: (i) ethanol, sulfanilamide, ref lux, 4 h; (ii) anhyd. K₂CO₃, dry acetone, approp. RNCO or RNCS, ref lux, 10–18 h; (iii) NaNO₂/CH₃COOH, stirring, 2 + 2 h; (iv) arylsulfonyl chloride, pyridine, ref lux, 4 h; (v) anhyd. K₂CO₃, dry acetone, RNCO, ref lux, 18 h; (vi) anhyd. K₂CO₃, dry acetone, RNCS, ref lux, 10 h.

Scheme 3.  Reagents and reaction conditions: (i) sulfanilamide, ethanol, ref lux, 4 h; (ii) RCHO, ethanol, ref lux, 3 h; (iii) HSCH₂COOH, dry dioxan, ref lux, 12 h; (iv) RNCO, anhyd. K₂CO₃, dry acetone, ref lux 18 h; (v) RNCS, anhyd. K₂CO₃, dry acetone, ref lux 10 h; (vi) ethyl bromoacetate, anhyd. NaOAc, abs. ethanol, ref lux, 2 h; (vii) phenacyl bromide, anhyd. NaOAc, abs. ethanol, ref lux, 2 h.

Table 1.  Minimal inhibitory concentrations (MIC, μg/mL) of the active newly synthesized compounds.

Compound number	S. aureus	B. subtilis	M. luteus	E. coli	P. aeruginosa	K. pneumoniae	C. albicans
3b	100	100	100	–	–	–	–
4c	50	100	100	100	–	–	–
5c	25	50	100	50	–	–	–
5d	25	50	50	50	–	100	100
5f	12.5	50	50	25	100	100	100
6a	12.5	50	50	25	100	100	50
6b	6.25	25	25	12.5	50	50	25
7a	25	25	100	50	100	–	–
8a	50	50	100	100	–	–	–
8b	25	100	50	50	–	–	100
9b	25	50	100	100	–	–	–
10	100	100	–	–	–	–	–
11b	50	100	100	50	–	–	–
11c	25	25	50	50	100	–	–
14b	50	25	100	25	50	–	–
15a	12.5	25	50	12.5	50	100	–
17	50	100	–	–	–	–	–
18b	12.5	25	50	25	50	50	25
18c	25	50	50	50	100	100	50
19c	50	50	100	25	50	100	25
20c	50	100	100	50	100	–	–
21b	50	50	100	100	100	–	–
21d	25	25	50	12.5	50	100	25
22b	12.5	25	50	50	100	100	50
22d	6.25	12.5	25	6.25	25	50	12.5
23d	12.5	50	50	25	100	–	100
A	6.25	12.5	12.5	6.25	12.5	12.5	–
C	–	–	–	–	–	–	6.25

(–): Totally inactive (MIC ≥ 200 μg/mL).

A: Ampicillin trihydrate (Standard broad spectrum antibiotic).

C: Clotrimazole (Standard broad spectrum antifungal agent).