Skip to main content
. Author manuscript; available in PMC: 2023 Feb 17.
Published in final edited form as: Front Trop Dis. 2023 Jan 23;3:1011124. doi: 10.3389/fitd.2022.1011124

Table 3:

Surveying the effects of variations at R3. Values highlighted in red are considered improved in comparison to initial lead compound rac-1.

graphic file with name nihms-1866382-t0002.jpg
Cpd R3 LD AMMAC EC50 (μM)a LD MAC EC50 (μM)b SI
MACc 		HEPG2 EC50 (μM) Solubilityd
(μM)		 AMPe
(nm/sec)		 HSAf
Binding
(%)		 PFIg
rac-1 isobutyl 2.5 15.8 6.3 63.1 107 345 96.4 8.4
9 isopentyl 2.5 31.6 12.6 79.4 15 100 98.0 9.1
10 neopentyl 2.5 25.1 10.0 39.8 36 170 97.4 9.0
11 n-butyl 0.1 2.5 25.0 50.1 49 370 96.7 8.4
12 graphic file with name nihms-1866382-t0003.jpg 1.6 3.2 2.0 50.1 135 410 97.5 8.1
13 graphic file with name nihms-1866382-t0004.jpg 0.5 1.6 3.2 50.1 52 370 96.8 8.5
14 graphic file with name nihms-1866382-t0005.jpg 6.3 20.0 3.2 50.1 17 270 97.9 8.9
15 graphic file with name nihms-1866382-t0006.jpg 6.3 25.1 4.0 50.1 6 360 98.0 9.7
16 graphic file with name nihms-1866382-t0007.jpg 5.0 7.9 1.6 25.1 17 130 97.8 10.6
17 graphic file with name nihms-1866382-t0008.jpg 4.0 7.9 2.0 15.8 <1 340 98.0 11.4
(a)

EC50 for growth inhibition of L. donovani intracellular amastigotes infecting THP-1 macrophages;

(b)

EC50 for cytotoxicity against host THP-1 macrophages;

(c)

SI MAC = selectivity index in macrophages, calculated as SI MAC = (LD MAC EC50)/(LD AMMAC EC50);

(d)

kinetic aqueous solubility as determined by high-throughput CLND (chemoluminescent nitrogen detection);

(e)

artificial membrane permeability;

(f)

human serum albumin binding;

(g)

PFI = ChromLogD7.4 + Aromatic rings