Efficient One-pot Synthesis of 3,3-di(indolyl)indolin-2-ones from Isatin and Indole Catalyzed by VOSO4 as Non-Sulfonamide Carbonic Anhydrase Inhibitors

Abstract

Background: A high yielding green protocol has been developed and delineated for the synthesis of 3,3- di(indolyl)indolin-2-ones, potentially bioactive compounds, involving one pot aqueous medium condensation of isatin with indole in the presence of VOSO4. The synthesized compounds were screened for their carbonic anhydrase inhibitory activity against human (h) isoforms hCA I, hCA II, hCA IX, and hCA XII. These non-sulfonamide derivatives selectively inhibited hCA II in the micromolar range. Objective: To develop a high yielding green protocol to synthesize 3,3-diindolyl oxindole derivatives using water as solvent media and screening the synthesized molecules for their carbonic anhydrase inhibitory activity. Methods: The target compound is obtained by taking isatin, indole, VOSO4, and H2O in one-pot at 70oC. Results: The designed molecules were synthesized by using the new method. The molecules were screened for their CA inhibitory activity, which shows selective inhibition toward hCA II.The result showed an excellent yield without any loss or decrease in catalytic activity, proving the catalyst's performance and recyclability. Conclusion: An efficient, simple, and green protocol was established that provides a facile and straightforward approach for the preparation of 3,3-diindolyl oxindole derivatives (3a-r) from Isatin and Indole by using 10 mol% VOSO4 in high yields in a short period of time by a one-pot coupling reaction. Furthermore, the catalyst can also be recovered and reused for three consecutive catalytic cycles without any loss of its efficiency, which was confirmed by performing the experiment with 3a. The newly synthesized molecules (3a-r) were screened for their carbonic anhydrase inhibition potency against four isoforms, hCA I, II, IX, and XII and most of the compounds were found potent against hCA II with potency low to submicromolar range.