New barbiturates and thiobarbiturates as potential enzyme inhibitors

Figures & data

Figure 1. Pharmacophore site combination. (X = O, S). PUI: Potential urease inhibitors (Y, Z = O, N, S); (PAB)/(PAF): potential antibacterial and antifungal inhibitors (Y, Z = O, N, S); (PKI): potential kinase inhibitors8.

Scheme 1. Synthesis of 1–27.

Scheme 2. Proposed fragmentation pattern of 8.

Table 1. Enzyme assays-Lipoxygenase; 28 quercetin (standard drug), DPPH radical scavenging; 29 baicalein (standard drug), Chymotripsin; 30 chymostatin (standard drug), Alpha-glucosidase; 31 acarbose (standard drug), Antiurease; 32 thiourea (standard drug).

Sr. no.	Inhibition %					IC50 (µmol.)
	DPPH	LOX	Chymotrypsin	α-Glucosidase	Anti-urease	DPPH	LOX	Chymotrypsin	α-Glucosidase	Anti-urease
1	39.85 ± 0.72	26.64 ± 0.31	50.38 ± 0.77	17.92 ± 0.36	12.65 ± 0.36	<500	<500	<500	<500	128.21 ± 0.14
2	53.86 ± 0.25	28.96 ± 0.11	46.82 ± 0.69	44.95 ± 0.55	−3.51 ± 0.55	<300	<500	<500	<500	<500
3	65.36 ± 0.34	28.18 ± 0.14	47.07 ± 1.10	1.56 ± 0.53	−2.59 ± 0.53	362.2 ± 0.18	<500	<500	<500	<500
4	85.31 ± 0.69	10.88 ± 0.31	38.42 ± 0.93	18.78 ± 0.16	−1.44 ± 0.16	94.41 ± 0.05	<500	<500	<500	<500
*5	44.38 ± 0.04	28.70 ± 0.11	43.00 ± 1.81	7.97 ± 0.52	−0.18 ± 0.52	<500	<500	<500	<500	<500
6	73.54 ± 0.34	45.87 ± 0.11	23.47 ± 1.31	29.62 ± 0.52	−6.76 ± 0.52	158.41 ± 0.14	<500	<500	<500	<500
7	90.57 ± 0.41	50.59 ± 0.22	7.00 ± 0.71	19.35 ± 0.85	− 3.27 ± 0.85	153.51 ± 0.34	<500	<500	<500	<500
8	73.99 ± 0.72	71.04 ± 0.21	25.82 ± 0.91	5.05 ± 0.73	−8.67 ± 0.73	172.21 ± 0.06	229.11 ± 0.03	<500	<500	<500
9	93.08 ± 0.41	83.36 ± 0.41	25.35 ± 0.59	32.15 ± 0.46	−7.45 ± 0.46	72.11 ± 0.63	138.71 ± 0.11	<500	<500	<500
10	92.23 ± 0.45	49.41 ± 0.24	31.94 ± 1.19	2.56 ± 0.12	−2.93 ± 0.12	63.11 ± 0.15	<500	<500	<500	<500
11	77.36 ± 0.44	52.95 ± 0.41	4.17 ± 1.17	15.22 ± 0.71	−0.03 ± 0.71	159.61 ± 0.82	<500	<500	<500	<500
12	92.54 ± 0.64	60.81 ± 0.72	65.63 ± 0.91	9.53 ± 0.76	3.95 ± 0.76	162.34 ± 0.34	407.11 ± 0.34	<500	<500	<500
13	46.23 ± 0.47	24.25 ± 0.22	64.13 ± 1.39	12.38 ± 0.88	−7.93 ± 0.88	<500	<500	159.3	<500	<500
14	46.81 ± 0.17	81.52 ± 0.34	27.73 ± 0.49	−2.56 ±0.78	−1.23 ± 0.78	74.41 ± 0.22	200.31 ± 0.60	<500	<500	<500
15	84.81 ± 0.78	85.19 ± 0.55	12.89 ± 1.66	26.17 ± 0.66	9.12 ± 0.66	79.91 ± 0.06	196.41 ± 0.44	<500	<500	<500
16	71.34 ± 0.22	18.87 ± 0.64	30.99 ± 0.61	−0.52 ± 0.84	0.19 ± 0.84	78.11 ± 0.05	<500	<500	<500	<500
17	91.82 ± 0.42	28.18 ± 0.14	17.71 ± 0.93	16.93 ± 0.55	−5.36 ± 0.55	82.33 ± 0.11	145.25 ± 0.35	<500	<500	<500
*18	51.98 ± 0.25	35.12 ± 0.52	78.62 ± 0.73	1.85 ± 0.92	−3.16 ± 0.92	<300	<500	12.8	<500	<500
19	40.21 ± 0.26	15.86 ± 0.77	78.62 ± 1.45	−3.041 ± 1.45	3.89 ± 1.45	<500	<500	<500	<500	<500
20	92.54 ± 0.64	81.26 ± 0.41	22.22 ± 1.29	9.96 ± 0.39	−7.40 ± 0.39	81.21 ± 0.07	198.21 ± 0.01	<500	<500	<500
21	83.77 ± 0.11	63.56 ± 0.71	−3.64 ± 0.23	−4.89 ± 0.27	3.88 ± 0.27	97.91 ± 0.31	378.11 ± 0.64	<500	<500	<500
22	82.08 ± 0.59	48.23 ± 0.21	−3.04 ± 1.65	− 3.85 ± 1.65	6.84 ± 1.65	93.71 ± 0.04	<500	<500	<500	<500
23	90.38 ± 0.31	70.25 ± 0.77	21.49 ± 0.99	12.38 ± 1.23	6.84 ± 1.23	70.91 ± 0.66	303.91 ± 0.18	<500	<500	<500
24	88.40 ± 0.31	62.39 ± 0.44	31.25 ± 0.49	20.91 ± 1.64	7.21 ± 1.64	99.51 ± 0.08	407.11 ± 0.67	<500	<500	<500
25	90.25 ± 0.14	61.34 ± 0.55	30.46 ± 0.63	6.12 ± 1.67	−2.25 ± 1.67	95.71 ± 0.05	329.71 ± 0.28	<500	<500	<500
*26	55.08 ± 0.24	9.83 ± 0.22	35.42 ± 1.69	42.53 ± 2.03	−5.96 ± 2.03	211.71 ± 0.18	<500	<500	<500	<500
27	86.51 ± 0.25	67.63 ± 0.41	1.14 ± 0.49	36.70 ± 0.56	3.58 ± 0.56	145.51 ± 0.31	376.81 ± 0.14	<500	<500	<500
28	92.68 ± 0.25					16.96 ± 0.14
29		93.26 ± 0.96					22.4 ± 1.3
30			92.60 ± 0.96					8.24 ± 0.11
31				92.60 ± 0.51					38.60 ± 0.15
***32					98.60 ± 0.51					21.25 ± 0.15

Methanol was used as solvent and concentration of all the samples was 0.5 mM, except in * and *** where concentration is 0.25 mM and 0.025 mM, respectively.

Rauf A, Liaqat S, Qureshi AM, et al. Synthesis, characterization and urease inhibition studies of 5-substituted-8-methyl-2H-pyrido[1,2-a]pyrimidine-2,4(3H)-diones. J Med Chem Res 2012;21:60–74

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