Synthesis and biological evaluation of novel series of aminopyrimidine derivatives as urease inhibitors and antimicrobial agents

Figures & data

Figure 1.  Pharmacologically active carbazole derivatives.

Scheme 1.  Reagents and conditions: (i) CH₃I, NaH, DMF, rt, 3 h; (ii) DMF, POCl₃, 80°C, 3 h; (iii) Substituted acetophenones, NaOH, Ethanol, rt, 24 h; (iv) Guanidine.HCl, DMF, NaH, 110°C, 10 h.

Table 1.  Urease inhibition activity.

Compound	IC50 ± SEM (µM)*
5a	>100
5b	95.4 ± 0.52
5c	30.7 ± 0.94
5d	73.7 ± 0.45
5e	>100
5f	40.2 ± 0.31
5g	45.2 ± 0.63
5h	>100
5i	19.4 ± 0.43
5j	23.2 ± 0.58
5k	28.1 ± 0.59
5l	95.1 ± 0.43
5m	87.2 ± 0.60
5n	>100
5o	>100
5p	83.7 ± 0.94
Thiourea	21.0 ± 0.14

*IC₅₀ values represent mean ± SD from three different experiments.

Table 2.  Antimicrobial activity of pyrimidine derivatives.

Compound	Antibacterial activity					Antifungal activity
	EC	BS	SA	SF	ST	CA	AN
5a	–	–	14	–	–	9	8
5b	–	11	11	13	–	14	12
5c	9	13	14	12	9	12	12
5d	–	10	10	8	–	9	–
5e	–	12	12	11	–	12	9
5f	–	16	11	10	–	13	10
5g	8	12	16	13	–	14	8
5h	–	9	8	9	–	8	8
5i	–	12	13	14	8	12	10
5j	9	13	14	12	–	9	9
5k	–	11	12	11	9	10	8
5l	–	10	13	10	–	–	–
5m	–	11	12	11	–	14	10
5n	8	9	10	12	–	9	–
5o	10	18	18	18	–	15	12
5p	9	12	15	14	–	10	8
Tetracycline	16	20	20	16	16	–	–
Nystatin	–	–	–	–	–	18	16

Concentration: 1 mg/mL in DMSO; Size of well 6 mm in diameter.

(–): Compounds showing no inhibition.

EC, E. coli; BS, B. subtilis; SA, S. aureus; SF, S. flexenari; ST, S. typhi; CA, C. albicans; AN, A. niger.

Table 3.  In silico pharmacological parameters for bioavailability.

Compounds	MW	c log p	HBA	HBD	PSA	MV	Drug likeness score
5a	350	4.69	2	2	42.54	332.76	−0.17
5b	380	4.75	3	2	50.92	364.61	0.85
5c	410	4.31	4	2	58.63	396.21	0.47
5d	440	4.15	5	2	66.85	425.79	−0.36
5e	368	4.81	2	2	42.54	338.68	−0.41
5f	386	4.45	2	2	42.54	343.60	−0.26
5g	386	4.96	2	2	42.54	343.99	−0.71
5h	384	5.38	2	2	42.54	349.96	−0.21
5i	418	5.85	2	2	42.54	365.33	0.03
5j	418	5.99	2	2	42.54	365.28	−0.43
5k	418	5.70	2	2	42.54	365.33	−0.35
5l	428	5.59	2	2	42.54	354.62	−0.72
5m	395	4.59	3	2	85.18	356.53	−0.51
5n	356	4.40	3	2	43.56	327.64	0.52
5o	351	3.43	3	2	51.86	327.04	−0.26
5p	365	3.86	2	4	63.62	340.34	−0.85

HBA, hydrogen bond acceptors; HBD, hydrogen bond donors; MV, molecular volume; PSA, polar surface area.