Identification of new compounds with high activity against stationary phase Borrelia burgdorferi from the NCI compound collection

Figures & data

Figure 1 Representative images at ×100 magnification of stationary phase B. burgdorferi treated with different compounds (50 μM) followed by staining with the SYBR Green I/PI assay. Abbreviations: DOX, doxycycline; AMO, amoxicillin; DAP, daptomycin; DAU, daunomycin; NOG, nogalamycin; PYR, pyrromycin; RHO, Rhodomycin A; CHA, chaetochromin; PRO, prodigiosin; MIT, mitomycin; NAN, nanaomycin; DAC, dactinomycin; EMO, emodin.

Table 2 Comparison of the MIC values and the activities of some compounds against stationary phase B. burgdorferi

Antibiotics	MIC (μg/mL)	Activity against stationary phase B. burgdorferi ^a (%)
Doxycycline	≤0.25	77
Amoxicillin	≤0.25	77
Daptomycin	12.5–25	18
Daunomycin 3-oxime	≤0.36	6
Daunorubicin	≤0.35	10
NSC299187	3.26–6.52	13
Pyronin B	1.8–3.6	19
Pyrromycin	0.37–0.73	21
Chaetochromin	2.74–5.47	22
Prodigiosin	≤0.2	24
Mitomycin	≤0.21	25
Nanaomycin	0.76–1.57	26
Dactinomycin	≤0.78	30

^aShown as the residual viable cell percentage from epifluorescence microscope counting data.

Figure 2 Representative images at ×100 magnification of stationary phase B. burgdorferi strain B31 treated with different compounds (20 μM) followed by staining with the SYBR Green I/PI assay. Abbreviations: DOX, doxycycline; DAP, daptomycin; DAU, daunomycin; NOG, nogalamycin; PYR, pyrromycin; RHO, Rhodomycin A; CHA, chaetochromin; PRO, prodigiosin; NAN, nanaomycin.

Table 3 Comparison of the activity of some hit compounds at 20 μM and 50 μM against stationary phase B. burgdorferi^a

		Residual viable cells (%)
NSC number	Compounds	20 μM^b	20 μM^c	50 μM^c
258812	Control	93	94	95
	Amoxicillin	77	77	77
	Doxycycline	76	77	77
	Daptomycin	32	25	18
	Dimethyldaunomycin hydrochloride	0	10	10
363998	Anthracene-9,10-dione, 1,5-bis[3-[[(2-hydroxyethyl)amino] propyl]amino]-9,10-dihydro-, dihydrochloride	22	14	13
70845	Nogalamycin	3	15	15
267229	Pyrromycin	6	20	21
136044	Rhodomycin A	5	21	21
345647	Chaetochromin	31	33	22
47147	Prodigiosin	0	45	24
267461	Nanaomycin	39	45	26
659997	Naphthalene-1,4-dione, 2-chloro-5,8-dihydroxy-3-(2-methoxyethoxy)-	40	50	28
224124	(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalene-2,3-diyl)dimethanediyl dicarbamate	54	77	31
617570	Benzoic acid, 2-hydroxy-, (2,6-pyridinediyldiethylidyne) dihydrazide, nickel complex	66	50	38
93739	2-Methyl-4,4′-[(4-imino-2,5-cyclohexadien-1-ylidene)methylene]dianiline hydrochloride	0	77	43

^aSeven-day-old stationary phase B. burgdorferi culture was treated with drugs for seven days.

^bResidual viable B. burgdorferi was calculated according to the regression equation and the ratio of Green/Red fluorescence obtained by the SYBR Green I/PI assay.

^cResidual viable B. burgdorferi was assayed by epifluorescence microscope counting.

Table 1 Activity of the top 30 active hits that had good activity (better than current clinical drugs) against stationary phase B. burgdorferi^a