Design, synthesis, antimicrobial activity and anti-HIV activity evaluation of novel hybrid quinazoline–triazine derivatives

Figures & data

Figure 1. The structures of DATA derivatives.

Figure 2. The design of quinazoline–triazine hybrid derivatives.

Scheme 1. Overview of the synthetic strategy for the synthesis of N²-cyclopropyl-N⁴-(2-(6,8-dibromoquinazolin-4-ylamino)ethyl)-6-R-1,3,5-triazine-2,4-diamine (7a–7s).

Table 1. Anti-HIV-1 and HIV-2 activity* (IC₅₀ and CC₅₀ in µg/mL) and cytotoxicity of compounds 6a–s and 7a–s in MT-4 cells.

Compound	Strain	IC50 (µg/mL)†	CC50 (µg/mL)‡	SI §
6a	III^B	>75.4	≥75.4	<1
	ROD	>75.4	≥75.4	<1
6b	III^B	>67.20	67.20	<1
	ROD	>67.20	67.20	<1
6c	III^B	>92.25	92.25	<1
	ROD	>92.25	92.25	<1
6d	III^B	>9.70	9.70	<1
	ROD	>9.70	9.70	<1
6e	III^B	>65.70	65.70	<1
	ROD	>65.70	65.70	<1
6f	III^B	>84.88	94.88	<1
	ROD	>84.88	94.88	<1
6g	III^B	>98.00	98.00	<1
	ROD	>98.00	98.00	<1
6h	III^B	>70.98	70.98	<1
	ROD	>70.98	70.98	<1
6i	III^B	>70.00	70.00	<1
	ROD	>70.00	70.00	<1
6j	III^B	>41.93	41.93	<1
	ROD	>41.93	41.93	<1
6k	III^B	>39.58	39.58	<1
	ROD	>39.58	39.58	<1
6l	III^B	>47.53	47.53	<1
	ROD	>47.53	47.53	<1
6m	III^B	>52.48	52.48	<1
	ROD	>52.48	52.48	<1
6n	III^B	>66.00	66.00	<1
	ROD	>66.00	66.00	<1
6o	III^B	>66.38	66.38	<1
	ROD	>66.38	66.38	<1
6p	III^B	>68.63	68.63	<1
	ROD	>68.63	68.63	<1
6q	III^B	>122	≥122	<1
	ROD	>122	≥122	<1
6r	III^B	>9.03	9.03	<1
	ROD	>9.03	9.03	<1
6s	III^B	>97.4	≥97.4	<1
	ROD	>97.4	≥97.4	<1
7a	III^B	>5.32	5.32	<1
	ROD	>5.32	5.32	<1
7b	III^B	>10.7	≥10.7	<1
	ROD	>10.7	≥10.7	<1
7c	III^B	>87.75	87.75	<1
	ROD	>87.75	87.75	<1
7d	III^B	>49.05	49.05	<1
	ROD	>49.05	49.05	<1
7e	III^B	>12.00	12.00	<1
	ROD	>12.00	12.00	<1
7f	III^B	>11.1	≥11.1	<1
	ROD	>11.1	≥11.1	<1
7g	III^B	>2.22	2.22	<1
	ROD	>2.22	2.22	<1
7h	III^B	>4.24	4.24	<1
	ROD	>4.24	4.24	<1
7i	III^B	>33.10	33.10	<1
	ROD	>33.10	33.10	<1
7j	III^B	>104.90	104.90	<1
	ROD	>104.90	104.90	<1
7k	III^B	>58.58	58.58	<1
	ROD	>58.58	58.58	<1
7l	III^B	>56.18	56.18	<1
	ROD	>56.18	56.18	<1
7m	III^B	>113.15	113.15	<1
	ROD	>113.15	113.15	<1
7n	III^B	>9.56	9.56	<1
	ROD	>9.56	9.56	<1
7o	III^B	>99.43	99.43	<1
	ROD	>99.43	99.43	<1
7p	III^B	>5.37	5.37	<1
	ROD	>5.37	5.37	<1
7q	III^B	>95.63	95.63	<1
	ROD	>95.63	95.63	<1
7r	III^B	>77.55	77.55	<1
	ROD	>77.55	77.55	<1
7s	III^B	>7.33	7.33	<1
	ROD	>7.33	7.33	<1
ddN/ddI¶	III^B	4.35	>50	>12
	ROD	6.96	>50	>7

*All data represent mean values for at least two separate experiments.

†Concentration required to protect the cells against viral cytopathogenicity by 50% in MT-4 cells.

‡Concentration that reduced the normal uninfected MT-4 cell viability by 50%.

§Selectivity index: ratio of CC50/IC50.

¶Standard drug.

Table 2. In vitro antimicrobial activity in MIC* (μg/mL) of compounds 6a–s and 7a–s.

	Gram +ve		Gram −ve		Fungal strains
	S. aureus	B. cereus	P. aeruginosa	K. pneumoniae	A. clavatus	C. albicans
Compound	MTCC 96	MTCC 430	MTCC 741	MTCC 109	MTCC 1323	MTCC 183
6a	200	200	100	100	200	200
6b	100	50	50	200	200	100
6c	25	100	50	25	50	50
6d	25	50	50	50	100	25
6e	100	200	200	100	100	200
6f	200	100	50	200	200	100
6g	100	100	200	100	100	100
6h	25	50	100	200	50	100
6i	100	25	200	100	25	100
6j	200	50	50	100	100	50
6k	100	200	100	200	200	100
6l	200	50	50	100	50	200
6m	100	100	200	100	200	100
6n	12.5	50	25	50	100	50
6o	50	200	200	50	50	25
6p	25	25	25	50	100	100
6q	50	100	50	50	50	50
6r	25	50	50	100	25	25
6s	25	12.5	25	50	50	100
7a	100	100	50	100	100	100
7b	100	100	12.5	100	100	100
7c	12.5	50	12.5	12.5	100	100
7d	6.25	50	12.5	12.5	50	50
7e	100	100	25	100	100	100
7f	100	100	12.5	100	100	100
7g	100	100	12.5	100	100	50
7h	12.5	25	100	100	100	100
7i	50	25	50	50	12.5	25
7j	100	100	100	100	100	100
7k	100	100	100	100	100	100
7l	100	50	50	100	100	100
7m	100	100	100	100	12.5	50
7n	6.25	12.5	12.5	25	25	25
7o	50	100	200	100	100	25
7p	12.5	12.5	12.5	12.5	50	50
7q	25	100	50	25	50	25
7r	6.25	25	50	12.5	12.5	25
7s	25	6.25	12.5	25	12.5	50
Ciprofloxacin†	3.125	3.125	3.125	3.125	–	–
Ketoconazole†	–	–	–	–	3.125	3.125
DMSO	–	–	–	–	–	–

Bold values indicates the most significant activity of the representative compound.

*MIC values are given in brackets. MIC (µg/mL) = Minimum inhibitory concentration.

†Standard.

Barré-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220:868–71

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