Synthesis, in-vitro Biological Evaluation, and Molecular Docking Study of Novel spiro-β-lactam-isatin Hybrids

In our ongoing search for bioactive compounds, a class of novel spiro-β-lactam isatin hybrids have been obtained by [2+2] cycloaddition reaction from 1-allyl-3-(arylimino)indolin-2-one and ketenes from various aryloxy acetic acids. The formation of all cycloadducts were confirmed by FTIR, 1H NMR, 13C NMR, and Mass spectra as well as elemental analyses. The new β-lactams were evaluated for their biological activities. The compounds 4a-g showed moderate to good activity against P. falciparum K1 strain and showed moderate to good activity. Among them, 4b and 4e demonstrated the best results with IC50 of 5.04 and 7.18, respectively. The molecular docking simulation of 4b with P. falciparum dihydrofolate reductase enzyme (PfDHFR) binding site shown several intermolecular interactions that would be consider to design the future analogs of antimalarial agents. Moreover, all the synthesized β-lactams were evaluated against some gram positive and gram negative bacteria including E. coli ATCC 28922, P. aeruginosa ATCC 27853 and S. aureus ATCC 25923 at the MIC level of 200 µg/mL and did not possess significant activity.