3-Benzylidene-4-chromanones: a novel cluster of anti-tubercular agents

Figures & data

Table 1. Evaluation of 1a–l against Mycobacterium tuberculosis H₃₇Rv.

Compound	Substituent in ring A	σ/σ* Value^a	π Values^b	% Inhibition^c
1a	2-Cl	0.37	0.71	71
1b	4-Cl	0.23	0.71	45
1c	2-Br	0.38	0.86	73
1d	3-Br	0.39	0.86	99
1e	4-Br	0.23	0.86	27
1f	2-OCH3	−0.22	−0.02	65
1g	3-OCH3	0.12	−0.02	98
1h	4-OCH3	−0.27	−0.02	59
1i	2,4-(OCH3)2	−0.49	−0.04	0
1j	3-CH3	−0.07	0.56	90
1k	4-CH3	−0.17	0.56	91
1l	4-N(CH3)2	−0.83	0.18	0

^aThe σ values are taken from reference 17 and the σ* constants from the literature18.

^bThe π constants are taken from the literature17.

^cThe figures indicate the percentage inhibition of Mycobacterium tuberculosis H₃₇Rv in the presence of 10 µg/mL of each compound. A reference drug rifampin inhibits the growth of this microorganism by 95% using a concentration of 0.25 µg/mL24.

Table 2. Evaluation of 1d, g, j and k against Mycobacterium tuberculosis H₃₇Rv and Vero cells.

		H37Rv		Vero cells
Compound	Substituent in ring A	IC50^a (µg/mL)	IC90^b (µg/mL)	EC50^c (µg/mL)	SI^d
1d	3-Br	0.56	0.77	19.8	25.7
1g	3-OCH3	<0.20	<0.20	9.92	>49.6
1j	3-CH3	0.46	0.72	30.8	42.8
1k	4-CH3	1.43	1.60	>100	>62.5

^aThe IC₅₀ figures are the concentrations of the compounds required to inhibit the growth of Mycobacterium tuberculosis H₃₇Rv by 50%.

^bThe IC₉₀ values are the concentrations of the compounds required to inhibit the growth of Mycobacterium tuberculosis H₃₇Rv by 90%. The minimal inhibitory concentration of rifampin is 0.2 µg/mL15.

^cThe EC₅₀ data are the concentrations of the compounds required to inhibit the growth of Vero cells by 50%. The EC₅₀ figure for rifampin is >100 µg/mL25.

^dThe letters SI refer to the selective index viz the quotients of the EC₅₀ and IC₉₀ values.

Figure 1. The general structure of the compounds in series 1–5. The nature of the R¹ and R² groups are presented in Tables 1 and 3.

Table 3. A comparison of the growth inhibition of most potent compounds in series 1 with the related analogs in series 2–5 against Mycobacterium tuberculosis H₃₇Rv.

	% Inhibition in different series^a
Substituents in ring A	1	2	3	4	5
3-Br	99	56	51	63	0
3-OCH3	98	0	79	8	0
3-CH3	90	40	78	19	0
4-CH3	91	0	75	0	3

^aThe data for series 1 are taken from Table 1. In the case of series 2–5, the figures indicate the percentage inhibition of Mycobacterium tuberculosis H₃₇Rv by using 12.5 µg/mL of each compound. A reference drug rifampin inhibits the growth of this microorganism by 95% using a concentration of 0.25 µg/mL24.

Figure 2. The general structures of the compounds proposed for analog development.

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