TABLE 2.

Structures of the 24 quinolones studied, in order of decreasing experimental and calculated IC₅₀s against T. gondii  

Quinolone	Basea	R1	R8	R5	R6	R7	IC50 (mg/liter)
							Exptl	Calculated
Trovafloxacin	B	2,4-Difluorophenyl		H	F	Azabicyclohexane	0.4	0.5
Grepafloxacin	A	Cyclopropyl	H	CH3	F	3′-Methylpiperazine	2.4	4.4
Gatifloxacin	A	Cyclopropyl	−OCH3	H	F	3′-Methylpiperazine	4.1	9.0
Moxifloxacin	A	Cyclopropyl	−OCH3	H	F	Piperidinopyrrolidine	5.1	2.5
Temafloxacin	A	2,4-Difluorophenyl	H	H	F	3′-Methylpiperazine	11.5	17.3
Clinafloxacin	A	Cyclopropyl	Cl	H	F	3′-Aminopyrrolidine	15.0	15.6
Acrosoxacin	A	−CH2CH3	H	H	H	4′-Pyridine	20.3	27.9
Enoxacin	B	−CH2CH3		H	F	Piperazine	20.3	26.1
Lomefloxacin	A	−CH2CH3	F	H	F	3′-Methylpiperazine	21.2	21.2
Rufloxacin	A	—b	—b	H	F	Piperazine	22.3	20.6
Irloxacin	A	−CH2CH3	H	H	F	Pyrrole	22.4	24.2
Piromidic acid	C	−CH2CH3		H		Pyrrolidine	26.2	40.7
Sparfloxacin	A	Cyclopropyl	F	NH2	F	3′,5′-Methylpiperazine	39.5	20.1
Flumequin	A	—c	—c	H	F	H	40.6	43.8
Fleroxacin	A	−CH2CH2F	F	H	F	4′-Methylpiperazine	46.8	44.6
Oxolinic acid	A	−CH2CH3	H	H	—d	—d	47.2	46.5
Norfloxacin	A	−CH2CH3	H	H	F	Piperazine	48.3	47.7
Ofloxacin	A	—e	—e	H	F	4′-Methylpiperazine	53.6	NCf
Nalidixic acid	B	−CH2CH3		H	H	CH3	73.6	68.7
Ciprofloxacin	A	Cyclopropyl	H	H	F	Piperazine	79.4	27.9
Pefloxacin	A	−CH2CH3	H	H	F	4′-Methylpiperazine	77.7	141.7
Pipemidic acid	C	−CH2CH3		H		Piperazine	116.4	39.3
Levofloxacin	A	—e	—e	H	F	4′-Methylpiperazine	159.6	NC
Cinoxacin	D	−CH2CH3	H	H	—d	—d	200.0	NC
K1g	B	2,4-Difluorophenyl		H	F	2-Methyl-6-amino-3aza-bicyclo[3.1.0.]hexyl	0.2	0.2
K2	B	2,4-Difluorophenyl		H	F	6-Aminomethyl-3aza-bicyclo[3.1.0.]hexyl	0.2	0.6
K3	B	2,4-Difluorophenyl		CH3	F	6-Amino-3-azabicyclo[3.1.0.]hexyl	0.3	0.1
K4	B	Cyclopropyl		H	F	6-Amino-3-azabicyclo[3.1.0.]hexyl	0.6	0.8
K5	B	2,4-Difluorophenyl		H	F	6-Amino-3-azabicyclo[3.1.0.]hexyl	0.9	0.4
K6	A	2,4-Difluorophenyl	H	H	F	6-Amino-3-azabicyclo[3.1.0.]hexyl	1.1	0.7
K7	B	2,4-Difluorophenyl		H	F	2-Methyl-6-aminomethyl-3aza-bicyclo[3.1.0.]hexyl	1.5	0.2
K8	B	2,4-Difluorophenyl		H	F	5-Amino-3-azabicyclo[3.1.0.]hexyl	3.0	5.2
K9	B	Cyclopropyl		H	F	6-Methylamino-3aza-bicyclo[3.1.0.]hexyl	4.3	1.0
K10	B	Cyclopropyl		H	F	5-Methylamino-3-azabicyclo[3.1.0.]hexyl	4.5	12.1
K11	B	2,4-Difluorophenyl		H	F	6-Methylamino-3aza-bicyclo[3.1.0.]hexyl	4.3	0.5

^aStructures A, B, C, and D represent the basic quinoline nucleus, 1,8-naphthyridine, pyrido[2,3-d]pyrimidine, and 1,2-cinnoline, respectively. 

^bR1-CH₂CH₂S-R8. 

^cR1-CH(CH₃)CH₂CH₂-R8. 

^dR6-O-CH₂-O-R7. 

^eR1-CH(CH₃)CH₂-O-R8. 

^fNC, not calculated. 

^gQuinolone structures K1 to K11 and IC₅₀s were described by Khan et al. (10).