Table 2.

The comparison in the substitution type and toxicity of several selected trichothecenes and their derivatives.

Trichothecenes	Substitution Positions and Types						Substitution Type a	Cytotoxicity		References
	C3	C12,13	C4	C7	C8	C15		Test Model	Relative IC50 b
	Positions for Type II Substitution		Positions for Type I Substitution (C4, C7, C8, C15)
DON	-OH	Epoxide	-H	-OH	=O	-OH	As a reference	-	1.0
T-2	-OH	Epoxide	-OAc	-H	-OCOCH2 CH (CH3)2	-OAc	Type I	3T3, Hep-G2, A549, HEp-2, Caco-2, A204, U937, Jurkat, RPMI8226, HUVEC	0.002–0.023	[33,34]
HT-2	-OH	Epoxide	-OH	-H	-OCOCH2 CH (CH3)2	-OAc	Type I	3T3, Hep-G2, A549, HEp-2, Caco-2, A204, U937, Jurkat, RPMI8226, HUVEC	0.011–0.046	[33,34]
DAS	-OH	Epoxide	-OAc	-H	-H	-OAc	Type I	SF-9 insect cell	0.011	[36]
15-Ac-DON	-OH	Epoxide	-H	-OH	=O	-OAc	Type I	3T3, Caco-2	1.0–1.1	[8,37]
Verrucarin A	-H	Epoxide	-OR	-H	-H	-OR	Type I	Vero, rat spleen lymphocytes	0.004–0.008	[35]
NIV	-OH	Epoxide	-OH	-OH	=O	-OH	Type I	3T3	0.79	[8]
3-Ac-DON	-OAc	Epoxide	-H	-OH	=O	-OH	Type II	3T3, Caco-2	2.1–10	[8,37]
DON-3-GlcAc	-OGlcAc	Epoxide	-H	-OH	=O	-OH	Type II	K562	>206	[38]
DON-GSH	-OH	-GSH	-H	-OH	=O	-OH	Type II	n.d. c	n.d.	[30]
3-epi-DON	-OH	Epoxide	-H	-OH	=O	-OH	NA d	3T3, Caco-2	357–1181	[39]
3-keto-DON	=O	Epoxide	-H	-OH	=O	-OH	NA	3T3, Caco-2	3.0–4.5	[39]
DOM-1	-OH	Epoxide	-H	-OH	=O	-OAc	NA	3T3, chicken lymphocytes	55–517	[8,40]

^a: DON was used as a reference trichothecene due to its relatively simple structure; type I: substituents either do not impact binding or introduced additional binding contacts; type II: substituents resulted in the steric hindrance for binding and impaired the corresponding binding contacts. ^b: IC₅₀ (the half-maximal inhibitory concentration) values relative to DON. ^c: n.d. means no data available. ^d: not applicable.