Synthesis, Docking and In Vitro Evaluation of Spiroindoline‐3,2’‐Quinazoline Derivatives

Abstract

AbstractThe Wang‐OSO3H catalyzed synthesis of a series of spiroindoline‐3,2’‐quinazoline derivatives and their in silico and in vitro evaluation against MtbCM (Mycobacterium tuberculosis Chorismate Mutase) are disclosed. Initially, a library of small molecules based on spiroindoline‐3,2’‐quinazoline framework was constructed. The reaction of 2‐aminobenzamide with appropriate isatin derivatives in the presence of Wang‐OSO3H under ultrasound irradiation was used for this purpose. The reaction proceeded under mild conditions to afford the desired products in good yields within a short duration. With the use of heterogeneous catalyst, inexpensive solvent as reaction media, and ultrasound as the source of green energy the methodology appeared to be a useful alternative to the previously reported methods. The in silico docking of all the synthesized compounds into the MtbCM (PDB: 2FP2) revealed that the binding of these compounds took place on the external surface pockets of the MtbCM active site cavity mainly in two different clusters. Three compounds that interacted well with MtbCM also showed good (57–64 %) inhibition of MtbCM in vitro when tested at 10 μM. Based on in silico and in vitro studies along with the ADME predictions these three spiroindoline‐3,2’‐quinazoline derivatives were identified as pre‐hits.