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. Author manuscript; available in PMC: 2024 Jun 10.
Published in final edited form as: J Med Chem. 2024 May 9;67(10):8323–8345. doi: 10.1021/acs.jmedchem.4c00517

Table 5.

In Vitro Antileishmanial Activity of TAs (117–124) with Modifications on Ring-A and Terminal Amine.

graphic file with name nihms-1993233-t0108.jpg survival (%) at 0.1 μMa
vs		 EC50 (nM)a
vs
compound R1 R2 L. mexicana
amastigote		 J774A.1
macrophage		 L. mexicana
amastigote		 J774A.1
macrophage		 TI
117 Et graphic file with name nihms-1993233-t0109.jpg 0.3 ± 0.1 52.5 ± 16.6 37.1 ± 1.82 512 ± 0.0 14
118 graphic file with name nihms-1993233-t0110.jpg graphic file with name nihms-1993233-t0111.jpg −0.02 ± 0.03 77.3 ± 45.3 18.8 ± 9.70 450 ± 20.1 24
119 graphic file with name nihms-1993233-t0112.jpg graphic file with name nihms-1993233-t0113.jpg 1.40 ± 0.20 86.6 ± 51.4 23.8 ± 15.9 717 ± 0.0 30
120 graphic file with name nihms-1993233-t0114.jpg graphic file with name nihms-1993233-t0115.jpg 0.010 ± 0.10 84.6 ± 46.6 22.6 ± 13.9 946 ± 687 42
121 graphic file with name nihms-1993233-t0116.jpg graphic file with name nihms-1993233-t0117.jpg −0.11 ± 0.02 84.6 ± 47.8 16.2 ± 6.24 959 ± 0.0 59
122 graphic file with name nihms-1993233-t0118.jpg graphic file with name nihms-1993233-t0119.jpg −0.11 ± 0.04 84.8 ± 63.4 15.8 ± 4.38 547 ± 0.0 35
123 graphic file with name nihms-1993233-t0120.jpg graphic file with name nihms-1993233-t0121.jpg −0.05 ± 0.04 59.6 ± 35.6 11.3 ± 2.04 > 1000 ± 0.0 > 88
124 graphic file with name nihms-1993233-t0122.jpg graphic file with name nihms-1993233-t0123.jpg 93.5 ± 26.6 101 ± 46 ND ND ND
miltefosine - - 0.020 ± 0.010 39.2 ± 5.1 3460 ± 781 >100000 ± 0.0 > 29
a

Data represent the mean ± standard deviation of results of at least two independent experiments; an error of 0.0 indicates identical values were obtained for each replicate; TI = Therapeutic Index (J774A.1 EC50/L. mexicana EC50); ND, not determined. Negative values for % survival represent luminescence measurements that were somewhat below that of background and probably reflect error in measurements of very low intensities. In some instances, e.g., 117 and 119, the rank order of % survival does not correspond to that of the EC50 values. The % survival for such compounds is also very low, and the EC50 values are likely more accurate, as they entail multiple measurements over a range of concentrations and luminescence values.