Solution-Phase Synthesis of Small Schiff Bases Combinatorial Library with Potential Antitubercular Activity
By Wesam S. Abdel-Aal, Hoda Y.Hassan, Tarek Aboul-Fadl , Adel F. Youssef
A model of small combinatorial library composed from five hydrazides (1-5) and five carbonyl derivatives (A-E) has been designed to formally generate subliberaries of 10 mixtures, M1-M10 comprising of 25 Schiff bases. Components of the designed liberary, 1-5(A-E), have been synthesized by solution-phase method and evaluated for their antitubercular activity against four Mycobacterium strains. Variable anti-TB activity was revealed with the investigated mixtures and maximum activity shown by M2 and M7 at a concentration of 50μg/ml. Individual compounds included in the library were synthesized and their anti-TB activity were determined. Compound 2B, predicted from the intersection of the active mixtures of M2 and M7, was the sole one that revealed anti-TB activity with the same MIC of the reference drug isoniazid (INH, 12.5 μg/ml). Other predicted compounds 1B, 3B and 1C-3Cpredicted from orthogonal cross matching of the less active subliberaries M1- M3, M7 and M8 were devoid of anti-TB activity at the tested concentrations when challenged in the pure state.
Keywords : Small combinatorial library, Heteroaryl hydrazides, Schiff Bases, Solution-Phase Synthesis, Antitubercular Activity