Synthesis and determination of antimycobacterial activity of tryptanthrine, vasicine, vasicinone and derivatives thereof

We describe the first application of the Niementowski quinazoline synthesis for the synthesis of vasicinone 3 (Fig.1), an alkaloid from Adhatoda vasica, a traditionally used plant in India for the treatment of respiratory diseases such as asthma and tuberculosis. This straightforward 2-step synthesis is an attractive basis for further medicinal chemistry work on vasicinone. Vasicine, vasicinone, deoxyvasicinone and deoxyvasicine were tested against Mycobacterium vaccae, a non-pathogenic mycobacterium closely related to Mycobacterium tuberculosis. Tryptanthrin, a related indoloquinazolinone from Strobilanthes cusia, showed antimycobacterial and antifungal activity as well as anti-proliferative activity.

Fig.1: Synthesis of vasicinone 3 via the Niementowski quinazoline synthesis.