In the present study, antileishmanial activity of sixteen novel series of tetrahydro-P-carboline derivatives against transgenic infrared fluorescent Leishmania infantum strain has been reported. Among these reported analogues, most of the compounds exhibited potent inhibition against both promastigote (IC50 from 1.99 +/- 1.40 to 20.69 +/- 0.95 mu M) and amastigote (IC50 from 0.67 +/- 0.05 to 4.16 +/- 0.008 mu M) forms of L. infantum. Moreover, compound 71, displayed most potent and selective inhibition of parasite amastigote form with IC50 0.67 +/- 0.05 mu M, selectivity index >298.5 and was comparable with standard drug amphotericin B. From this study, a new class of tetrahydro-beta-carboline derivatives with potent antileishmanial activity was identified and it needs further extensive study to optimize the lead molecules to win the battle against severe and neglected disease leishmaniasis. (C) 2016 Elsevier Masson SAS. All rights reserved.