Natural Product Inspired Synthesis of Tryptanthrin Analogues as Potential Antimalarial Agents

Abstract

A new series of tryptanthrin analogues have been synthesized as potential antimalarial molecules. Synthesis of tryptanthrin aminoalkyl derivatives have been achieved via alkylation of oxime functionality of tryptanthrin derivatives by various alkyl amino pharmacophoric chains. 21-Membered small library of tryptanthrin aminoalkyl analogues were synthesized with variation in both parent natural alkaloid and in amino alkyl side chains. Synthesized compounds were fully characterized with 1H & 13C NMR, IR spectroscopy. Further all the members were screened for their antimalarial potential against Plasmoum falciparum in both sensitive (3D7) and in resistant (k1) strains. Most of the screened compounds were exhibited potent antimalarial activity in both strains. Compounds (5m, 3c and 5l) having nitro group at the 8 position in tryptanthrin framework were most promising compounds in series (IC50 = 10 nm) with IC50 value as low as 10 nm comparable to chloroquine. These compounds were also tested for their toxic effect and found to be highly safe with very high value of SI index.