Design of potent fluoro-substituted chalcones as antimicrobial agents

Figures & data

Figure 1. Comparative analysis of the antitubercular activity of the synthesized compounds and the standard drugs EMB and INH.

Scheme 1. General structures of synthesized compounds.

Scheme 2. Preparation of non- and fluoro-substituted trimethoxy/trihydroxy chalcones. Reagents and conditions: (i) 50% KOH, MeOH, (ii) H₂, Pd-C, EtOH, (iii) 50% KOH, MeOH, (iv) H₂, Pd-C, EtOH, (v) DIPEA, MOMCl, DCM, (vi) 50% KOH, MeOH, (vii) 12M HCl, EtOAc, (viii) H₂, Pd-C, EtOH.

Table 1. Substitution patterns and antitubercular activity of target compounds (3, 4, 9–15, and 20–23).

Compound	Main structure	R	R^1	cLog p^a
3	C	Me	H	3.21
4	D	Me	H	3.23
9	C	Me	2-F	3.36
10	C	Me	3-F	3.36
11	C	Me	4-F	3.36
12	C	Me	2,5-di F	3.52
13	E	Me	2-F	4.74
14	E	Me	3-F	4.74
15	E	Me	2,5-di F	4.90
20	C	H	2-F	2.57
21	C	H	2,5-di F	2.73
22	E	H	2-F	2.59
23	E	H	2,5-di F	2.75

^a cLog p value of the synthesized compounds calculated using ChemBioDrawUltra 12.0.3.

Table 2. MICs of compounds 3, 4, 9–15, and 20–23 and the standard ampicillin against the selected bacterial strains.

	Minimal inhibitory concentration, MIC (μg/mL)
Compounds	S. aureus	S. pyogenes	E. faecalis	E. coli	P. aeruginosa
3	31.25	31.25	31.25	31.25	62.5
4	62.5	31.25	62.5	31.25	31.25
9	62.5	62.5	31.25	62.5	62.5
10	125	62.5	125	125	125
11	62.5	62.5	62.5	125	125
12	15.6	62.5	31.25	62.5	62.5
13	62.5	62.5	31.25	31.25	62.5
14	62.5	62.5	31.25	62.5	62.5
15	125	125	62.5	125	125
20	125	125	125	125	125
21	62.5	125	125	125	125
22	125	125	125	125	125
23	7.8	62.5	125	125	125
Ampicillin	-	-	62.5	3.9	31.25

?: All tested concentrations are active.

Table 3. MICs of compounds 3, 4, 9–15, 20–23 and the standard fluconazole against selected fungi.

	Minimal inhibitory concentration, MIC (μg/mL)
Compounds	C. albicans	C. glabrata	C. parapsilosis
3	15.62	31.25	62.5
4	62.5	62.5	62.5
9	250	250	62.5
10	125	62.5	62.5
11	62.5	62.5	62.5
12	125	125	62.5
13	125	31.25	31.25
14	125	125	62.5
15	62.5	31.25	31.25
20	15.62	62.5	62.5
21	125	125	62.5
22	31.25	31.25	31.25
23	250	125	62.5
Fluconazole	-	31.25	-

?: All tested concentrations are active.

Figure 2. Some natural anti-tubercular agents.