TABLE 1.

MICs of CPT, nitidine, and their derivatives for S. cerevisiae wild type, Δerg6, Δerg6 Δtop1, and Δerg6 Δtop1 and C. neoformans topoisomerase I^a

Compound	Structure	MIC (μg/ml)
		Wild type	Δerg6	Δerg6 Δtop1	Δerg6 Δtop1 + CnTOP1
1 (CPT)	R1 = R2 = R3 = H	>100	6.25	>100	0.19
2 (CPT-gly)	R1 = R2 = H; R3 = COCH2NH2 · HCl	6.25	6.25	>100	0.39
3 (9-amino-CPT)	R1 = R3 = H; R2 = NH2	>100	>100	>100	12.5
4 (irinotecan; CPT-11)	R = 4-[(piperidinopiperidino) carbonyl]-oxy; R1 = R3 = H; R2 = Et	>2,000	500	>2,000	500
5 (TPT)	R = R2 = R3 = H; R1 = (dimethylamino)methyl	>1,000	>1,000	>1,000	50
6 (10-hydroxy-CPT)	R = R1 = R2 = R3 = H	>100	>100	>100	>100
7 (10-hydroxy-CPT-gly)	R = R1 = R2 = H; R3 = COCH2NH2 · HCl	>100	>100	>100	25
8 (10-hydroxy-7-ethyl-CPT)	R = R1 = R3 = H; R2 = C2H5	>100	>100	>100	>100
9 (10-hydroxy-7-ethyl-CPT-gly)	R = R1 = H; R2 = C2H5; R3 = COCH2NH2 · HCl	>100	>100	>100	50
10 (10,11-MD-20 (R)-CPT)	R1 = R2 = R3 = H	>100	>100	>100	>100
11 (10,11-MD-20 (S)-CPT)	R1 = R2 = R3 = H	>100	>100	>100	≤0.09
12 (10,11-MD-20 (S)-CPT-gly)	R1 = R2 = H; R3 = COCH2NH2 · HCl	3.12	0.19	>100	≤0.09
13 (9-amino-10,11-MD-20 (S)-CPT)	R1 = NH2; R2 = R3 = H	>100	>100	>100	1.56
14 (9-amino-10,11-MD-20 (S)-CPT-gly	R1 = NH2; R2 = H; R3 = COCH2NH2 · HCl	6.25	3.12	>100	0.78
15 (7-chloromethyl-10,11-MD-20 (S)-CPT)	R1 = R3 = H; R2 = CH2Cl	3.12	3.12	>100	≤0.09
16 (7-chloromethyl-10,11-MD-20 (S)-CPT-gly)	R1 = H; R2 = CH2Cl; R3 = COCH2NH2 · HCl	3.12	3.12	>100	0.19
17 (7-methyl-10,11-MD-20 (S)-CPT)	R1 = R3 = H; R2 = CH3	>100	>100	>100	0.78
18 (nitidine chloride)		6.25	1.56	3.12	3.12
19 (6-ethoxy-5,6-dihydronitidine)		3.12	1.56	3.12	3.12
20 (nitidine cyclic analog)		50	25	50	50

^aAbbreviations: CnTOP1, C. neoformans topoisomerase 1; Me, methyl; MeO, methanol; Et, ethyl; gly, glycinate.