5-Nitroisatin-derived thiosemicarbazones: potential antileishmanial agents.

A series of 29 previously reported N(4)-substituted 5-nitroisatin-3-thiosemicarbazones 2-30 has been screened for leishmanicidal potential. Compounds 2-4, 7, 8, 10-13, 15-19, 21, 23, 24, 26, 28 and 30 exhibited good to excellent antileishmanial activities with IC50 values ranging from 0.44 ± 0.02 to 32.38 ± 0.66 µg/mL. Of these, 5, 7, 19 and 28 proved to be the most active antileishmanial agents, displaying activities with IC50 values 1.78 ± 0.35, 0.44 ± 0.02, 1.91 ± 0.04 and 4.28 ± 0.75 µg/mL, respectively, which were even better than the standard drug, pentamidine (IC50 = 5.09 ± 0.04 µg/mL). This study presents the first example of exhibition of leishmanicidal potential by isatin-thiosemicarbazones and as such furnishes a solid basis for further research on these compounds to develop more potent antileishmanial agents.

(Z)-4-(3-Fluoro-phen-yl)-1-(5-nitro-2-oxo-indolin-3-yl-idene)thio-semicarbazide.

In the title compound, C(15)H(10)FN(5)O(3)S, an intra-molecular N-H⋯N hydrogen bond generates an S(5) ring, whereas N-H⋯O and C-H⋯S inter-actions complete S(6) ring motifs. The dihedral angle between the isatin ring system and the fluoro-benzene ring is 5.96 (6)° and the complete mol-ecule is close to planar (r.m.s. deviation for all the non-H atoms = 0.112 Å). In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds to form C(8) chains along the [100] direction and C-H⋯O inter-actions are also observed.

(Z)-4-Hexyl-1-(5-nitro-2-oxo-2,3-dihydro-1H-indol-3-yl-idene)thio-semicarbazide.

In the title compound, C(15)H(19)N(5)O(3)S, intra-molecular N-H⋯O, N-H⋯N and C-H⋯S inter-actions occur and the three terminal C atoms of the hexyl group are disordered over two sites with an occupancy ratio of 0.664 (12):0.336 (12). In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds occur and C-H⋯O bonds link the dimers into chains. A short C=O⋯π contact is also present.

1-(5-Nitro-2-oxoindolin-3-yl-idene)-4-o-tolyl-thio-semicarbazide methanol monosolvate.

In the title compound, C(16)H(13)N(5)O(3)S·CH(4)O, the dihedral angle between the isatin unit and the 2-methyl-phenyl group is 41.81 (2)° and intra-molecular N-H⋯O and N-H⋯N hydrogen bonds occur, generating S(6) and S(5) rings, respectively. In the crystal, polymeric chains arise as a result of N-H⋯O, O-H⋯S and C-H⋯O inter-actions.