Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents

Figures & data

Figure 1.  Biologically active natural and synthetic carbazole derivatives.

Scheme 1.  Reagents and conditions: (i) DMF, NaH, CH₃I, rt, 3 h; (ii) DMF, POCl₃, 80°C, 4 h; (iii) Substituted acetophenones, NaOH, ethanol, rt, 24–36 h.

Table 1.  Radical scavenging activity of carbazole chalcones.

		DPPH radical scavenging activity		Hydroxyl radical scavenging activity
Compounds	R	Inhibition (%)	IC50 (μg/mL)	Inhibition (%)	IC50 (μg/mL)
12a	H	72.69	70.15	86.84	51.10
12b	4-OCH3	18.65	ND	32.33	ND
12c	3,4-OCH3	83.84	52.49	69.54	ND
12d	2,4,6-OCH3	61.92	ND	87.59	38.60
12e	4-F	70.76	ND	91.72	35.15
12f	2,4-F	79.03	67.50	61.65	ND
12g	3,4-F	83.07	60.45	78.19	56.10
12h	4-Cl	76.34	68.15	63.90	ND
12i	2,4-Cl	82.30	61.45	74.06	ND
12j	3,4-Cl	59.61	ND	83.83	54.34
12k	2,5-Cl	75.57	ND	63.90	ND
12l	4-Br	73.65	ND	79.32	56.15
12m	4-NO2	89.53	47.10	88.34	36.63
12n	2-Thiophene	82.88	60.45	71.42	ND
12o	2-pyridine	87.50	50.65	54.51	ND
Ascorbic acid^a	—	95.76	45.94	88.34	48.45

The results summarised for inhibition (%) are mean values of two parallel experiments.

Inhibition (%) activity tested at 100 μg.

IC₅₀ values represent mean ± standard deviation from three different experiments.

ND, Not determined.

^aStandard.

Figure 2.  Agarose gel electrophoresis pattern of pUC 18 DNA strand breakage by 2,2′-azobis (2-amidinopropane hydrochloride) (AAPH) and inhibited by carbazole chalcones. Supercoiled plasmid DNA was incubated with AAPH and/or carbazole chalcones in phosphate-buffered saline (pH 7.4) at 37°C for 1 h. Lane 1: DNA strand breakage induced by AAPH at 10 mM; Lane 2: control super coiled DNA; Lane 3: compound 12g; Lane 4: 12a; Lane 5: 12e; Lane 6: 12n and lane 7: 12m.

Table 2.  Cytotoxicity of carbazole chalcones.

Compounds	Hep 3BPN7	SRHep 3BPN7	HL60 P58	SRHL60 P58	HeLa B75	SRHeLa B75	PN-15C-12	SRaverage
12a	70.33	1.63	57.73	1.34	75.44	1.75	42.95	1.57
12b	63.40	3.56	62.52	3.51	71.26	4.01	17.78	3.69
12c	72.80	2.37	59.32	1.93	73.31	2.39	30.69	2.23
12d	65.60	2.27	49.07	1.70	78.39	2.72	28.85	2.23
12e	69.40	2.12	56.80	1.73	77.09	2.35	32.80	2.06
12f	62.40	2.92	57.89	2.58	62.27	2.78	22.39	2.76
12g	61.53	3.16	55.79	2.86	56.31	2.89	19.49	2.97
12h	67.86	1.81	60.50	1.61	80.58	2.15	37.54	1.85
12i	66.93	2.94	55.12	2.42	76.74	3.37	22.79	2.90
12j	65.10	3.86	51.17	3.03	78.73	4.67	16.86	3.85
12k	61.40	4.36	66.63	4.73	56.31	3.99	14.09	4.36
12l	70.73	1.61	64.28	1.46	75.85	1.73	43.87	1.60
12m	69.46	2.18	58.31	1.83	74.89	2.35	31.88	2.12
12n	70.60	2.54	59.07	2.12	73.89	2.66	27.79	2.44
12o	67.66	2.28	62.85	2.12	65.36	2.20	29.64	2.20
Methotrexate	64.60	1.20	54.08	1.00	78.66	1.46	53.85	1.22

The results are the mean values of n = 2.

SR = Inhibition of cancer cell line (%)/Inhibition of normal cell line (%).

Hep 3BPN7, liver cancer cell line; HL60 P58, leukaemia cancer cell line; HeLa-B75, cervix cancer cell line; PN-15C-12, normal liver cell line, compounds tested at 100 μg; SR, selectivity ratio.