Antituberculer Schiffs Bases Prepared from Biologically Active Substituted Benzaldehydes to Enhance Drug likeness

In a preliminary screening we found that many substituted benzaldehyde showing promising anti-tubercular (anti-TB) activity. Study was planned to convert these substituted benzaldehyde to anti-tubercular schiffs bases. Various schiffs bases were synthesized by condensation of 2-Amino pyridine (or its derivative) or Thiophene or Furoic or Nicotinic acid hydrazide with anti-tubercular benzaldehydes. Compounds were purified, crystallized and characterized by IR,¹H and ¹³C-NMR. Initial Anti-tubercular screening was carried out in fast growing Mycobacterial strain Mycobacterium smegmatis (M. smeg.) by disc diffusion method. Further quantitative estimation of anti-tubercular activity was carried out in Mycobacterium bovis (M. bovis) BCG vaccine strain using Resazurin Microplate Assay (REMA). Schiffs bases prepared from salisaldehyde or p-NO2 benzaldehyde with 2- amino pyridine (3c and 3f) and 2, 3 dihydroxy benzaldehyde with nicotinic acid hydrazide (8a) have shown anti-TB potential. Anti-TB activity of synthesized compounds was reported at higher concentration (500µg/mL) with respect to standard drug isoniazid INH (40µg/mL), because there was no earlier report or MIC data of synthesized Schiffs bases. Compounds 3c, 3f and 8a have shown 60, 40 and 50 mm zone of inhibition in M. smegmatis compared to vector control, INH has shown 40 mm zone of inhibition. In Mycobacterium bovis, Schiffs bases 3c,3f and 8a have shown 53.69, 49.41, 46.49 % inhibition at 500 µM concentration, the activity was concentration dependent and lower inhibition of 29.73, 37.75 and 36.15% were observed at 125 µM concentration by the compound 3c and 3f and 8a respectively. Standard drug INH has shown 60% inhibition at 40 µg/ml concentration. The anti-TB activity of banzaldehydes depends on various substitutions, Nitro or methoxy or hydroxyl substituted benzaldehydes were anti-TB while halogenated benzaldehydes are inactive. Preparation of Schiff’s bases may be one of the ways to enhance activity, introduce drug likeness in the active benzaldehyde, may represent low toxicity and high bioavailability.

Source:: http://www.pubs.iscience.in/journal/index.php/cbl/article/view/818