A catalyst-free one-pot four component methodology for the synthesis of 1,2,4,5-substituted imidazoles under conventional heating and microwave irradiation using 1-butyl-3-methylimidazolium bromide, [Bmim]Br, as a neutral reaction media is described. A broad range of structurally diverse aldehydes (aromatic aldehydes bearing electron withdrawing and/or electron releasing groups as well as heteroaromatic aldehydes) and primary amines (aromatic and aliphatic) were applied successfully, and corresponding products were obtained in good to excellent yields without any byproduct.

Highly diastereoselective synthesis of chromeno β-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired β-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4hydroxycoumarin in the presence of 1,4-diazabicyclo[2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1 H NMR, 13 C NMR spectral data and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. β-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. β-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.

In our ongoing search for bioactive compounds, a class of novel spiro-β-lactam isatin hybrids has been synthesized through a [2+2] cycloaddition reaction from 1-allyl-3-(arylimino)indolin-2-one, ketenes and various aryloxy acetic acids. The formation of all cycloadducts was confirmed by FTIR, 1 H NMR, 13 C NMR, and mass spectroscopy as well as elemental analyses. The new βlactams were subsequently evaluated for their biological activities demonstrating moderate to good activities against P. falciparum K1 strain. Among them, 4b and 4e lead to the best results with IC 50 of 5.04 and 7.18 µM, respectively. The molecular docking simulation of 4b with P. falciparum dihydrofolate reductase enzyme (PfDHFR) binding site presented several important intermolecular interactions. All the synthesized β-lactams were also evaluated for their antimicrobial activities against both Gram-positive (S. aureus ATCC 25923) and Gram-negative bacteria (E. coli ATCC 28922, P. aeruginosa ATCC 27853) but unfortunately MICs up to 200 µg/mL were encountered in all cases.

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