Alkyl gallium(III) quinolinolates: A new class of highly selective anti-leishmanial agents

A series of eight alkyl gallium complexes of general formulae [GaMe2(L)] and [Ga(Me)(2)L] have been synthesised, characterised and their antimicrobial activity against bacteria, cancer cells and Leishmania assessed. All eight complexes are novel, with the solid-state structures of all complexes successfully authenticated by single crystal X-ray diffraction. The dimethyl complexes all adopt a four-coordinate tetrahedral confirmation, while the monomethyl complexes are five-coordinate trigonal bipyramidal. All complexes were screened for their anti-bacterial activity either by solution state diffusion, or a solid-state stab test. The five soluble complexes underwent testing against two differing mammalian cell controls, with excellent selectivity observed against COS-7 cells, with an IC50 range of 88.5 mu M to >= 100 mu M. Each soluble complex was also tested for their anti-cancer capabilities, with no significant activity observed. Excellent activity was exhibited against the protozoan parasite Leishmania major (strain: V121) in both the promastigote and amastigote forms, with IC50 values ranging from 1.11 mu M -13.4 mu M for their anti-promastigote activity and % infection values of 3.5% +/- 0.65-11.5% +/- 0.65 for the more clinically relevant amastigote. Selectivity indices for each were found to be in the ranges of 6.61 -64.7, with significant selectivity noted for two of the complexes. At minimum, the gallium complexes show a 3-fold enhancement in activity towards the Leishmaniaamastigotes over the parent quinolinols alone. (C) 2019 Elsevier Masson SAS. All rights reserved.