Elucidation of the glycosylation steps during biosynthesis of antitumor macrolides PM100117 and PM100118 and engineering for novel derivatives

Table 1 In vitro cytotoxic activity of compounds 1–13

Compound		A549 (μM)	HT29 (μM)	MDA-MB-231 (μM)	PSN1 (μM)
1 PM100117	GI₅₀	1.52	3.04	2.66	nd
	TGI	1.84	3.23	2.79	nd
	LC₅₀	2.22	3.61	2.97	nd
2 PM100118	GI₅₀	2.24	1.92	1.73	nd
	TGI	3.13	2.81	2.75	nd
	LC₅₀	4.28	4.09	4.16	nd
3 From mutant ΔgonCM	GI₅₀	1.94	5.03	4.06	2.97
	TGI	2.39	6.07	6.39	3.23
	LC₅₀	3.16	>6.45	>6.45	>6.45
4 From mutant ΔgonCM	GI₅₀	2.02	5.22	4.39	3.13
	TGI	2.58	6.76	5.78	3.41
	LC₅₀	>6.97	>6.97	>6.76	>6.97
5 From mutant ΔgonD3	GI₅₀	>6.82	>6.82	>6.82	>6.82
	TGI	nd	nd	nd	nd
	LC₅₀	nd	nd	nd	nd
6, 7, 8 and 9 From mutant ΔgonE ^a	GI₅₀	>10.70	>10.70	>10.70	>10.70
	TGI	nd	nd	nd	nd
	LC₅₀	nd	nd	nd	nd
10 From mutant ΔgonG1	GI₅₀	>10.70	>10.70	>10.70	>10.70
	TGI	nd	nd	nd	nd
	LC₅₀	nd	nd	nd	nd
11 and 12 From mutant ΔgonG2 ^a	GI₅₀	>9.20	>9.20	>9.20	>9.20
	TGI	nd	nd	nd	nd
	LC₅₀	nd	nd	nd	nd
13 From mutant ΔgonG3	GI₅₀	>6.90	>6.90	>6.90	>6.90
	TGI	nd	nd	nd	nd
	LC₅₀	nd	nd	nd	nd

^aThese compounds were assayed individually
GI ₅₀ compound concentration that produces 50% inhibition on cell growth as compared to control cells, TGI compound concentration that produces total growth inhibition as compared to control cells, LC ₅₀ compound concentration that produces 50% cell death as compared to control cells, nd values not determined

ISSN: 1475-2859