Anti-Inflammatory and Anticancer Activities of New Monocyclic Indolo β-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, ¹H NMR, ¹³C NMR spectral data, and elemental analysis. The diastereoselectivity (cis stereoisomer) of these novel β-lactam hybrids was confirmed based on ¹H 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 >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 (IC₅₀ of 14.17, 10.95, 12.49 µM), showed more activity than the reference, Cisplatin (IC₅₀ 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.