ИСТИНА

In a continuation of our research into transformations1 of 2-arylideneindoxyls (hemiindigos) 1 we developed novel continuous-flow cascade reactions for producing 1,4-diaryl-disubstituted dipolar γ-carbolines 2 bearing a carboxylate group and their two indole-fused pentacyclic precusors 3, 4. The γ-carboline skeleton is widely used in the design of agents against various diseases and represents a basic core of many clinically successful drugs. The synthetic utility and potential applications of 3, 4 were demonstrated by the initial antimycobacterial activity studies. The conjugated system of 3, 4 resembles the ring system of rimino-compounds including antileprotic and antimycobacterial drug clofazimine possessing unprecedentedly high activity against drug-resistant and dormant tuberculosis. The promising in vitro antimycobacterial activity of 3, 4 against both Mycobacterium tuberculosis H37Rv and isoniazid-resistant human isolate CN-40 was identified. It is believed that just the ring system of both rimino-compounds and 3, 4 is responsible for the unique mechanism of their action. We hope the new scaffold we have found will be useful in developing lead agents against multidrug-resistant/dormant tuberculosis.