Microwave-Assisted Solution-Phase Synthesis and DART-Mass Spectrometric Monitoring of a Combinatorial Library of Indolin-23-dione Schiff Bases with Potential Antimycobacterial Activity

摘要

A combinatorial library composed of eleven hydrazides >A-K and eleven indolin-1,2-dione derivatives >1-11 has been designed to formally generate sublibraries of 22 mixtures, >M1-M22 comprising of 121 Schiff bases, >A-K(>1-11). The designed library has been synthesized by the solution-phase method and microwave-assisted synthetic techniques. The formation of individual compounds of each mixture was confirmed by Direct Analysis in Real Time (DART) as ionization technique connected to an Ion Trap as a mass detector. The synthesized mixtures were evaluated for their antimycobacterial activity against four Mycobacterium strains; M. intercellulari, M. xenopi, M. cheleneoi and M. smegmatis. Variable antimycobacterial activity was revealed with the investigated mixtures and maximum activity was shown by >M8, >M10, >M11, and >M15 with MIC values of 1.5, 3.1, 6.2 and 0.09 μg/mL, respectively. Application of the indexed method of analysis on these active mixtures revealed that compounds >D8, >D10 and >D11 may contribute to the activity of the tested mixtures.