Anti‐Inflammatory and Anticancer Activities of New Monocyclic Indolo <i>β</i> ‐Lactam Hybrids

Abstract The diastereoselective synthesis of N ‐protected indolo β ‐lactam hybrids 5a‐n by a classic [2 + 2] Staudinger reaction and the study of their anti‐inflammatory and anticancer activities are reported in this paper. The structures of these new compounds were confirmed based on IR, 1 H NMR, 13 C NMR spectral data, and elemental analysis. The diastereoselectivity ( cis stereoisomer) of these novel β ‐lactam hybrids was confirmed based on 1 H NMR. The in‐vitro anti‐inflammatory activity was investigated for these synthesized compounds. Compounds 5b , 5d , 5m , and 5n showed good anti‐inflammatory activities. Compound 5d with an anti‐inflammatory ratio of &gt;53.70 was the most active one compared to dexamethasone with an anti‐inflammatory ratio of 37.78 as reference. The molecular docking studies revealed that 5d displayed the best score among the synthesized compounds, indicating a potentially stronger and more stable binding with the iNOS enzyme's active site. Therefore, it can be regarded as a potential candidate for anti‐inflammatory purposes. In anticancer studies, imines 4b and 4c exhibited the most activity against A549 (lung), AGS (gastric), and MDA‐MB‐468 (breast) cancer cell lines. Imine 4b (IC 50 of 14.17, 10.95, 12.49 µM), showed more activity than the reference, Cisplatin (IC 50 of 20.76, 14.95, 20.97 µM) toward these cell lines respectively. Indolo β ‐lactams, 5h and 5l exhibited good activity toward the AGS cell line. Both compounds 4c and 5l with an allyl group had a less toxic effect than 4b and 5h having a benzyl group.