Synthesis, in-vitro biological evaluation, and molecular docking study of novel spiro-beta-lactam-isatin hybrids

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Jarrahpour A., Jowkar Z., Haghighijoo Z., Heiran R., Rad J. A., Sinou V., ...More

MEDICINAL CHEMISTRY RESEARCH, vol.31, no.6, pp.1026-1034, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 31 Issue: 6
  • Publication Date: 2022
  • Doi Number: 10.1007/s00044-022-02898-8
  • Journal Name: MEDICINAL CHEMISTRY RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, Veterinary Science Database
  • Page Numbers: pp.1026-1034
  • Keywords: 2-azetidinone, isatin, in-silico study, antimalarial activities, Staudinger reaction, AGENTS, MONO
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

In our ongoing search for bioactive compounds, a class of novel spiro-beta-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, H-1 NMR, C-13 NMR, and mass spectroscopy as well as elemental analyses. The new beta-lactams 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 IC50 of 5.04 and 7.18 mu M, respectively. The molecular docking simulation of 4b with P. falciparum dihydrofolate reductase enzyme (PfDHFR) binding site presented several important intermolecular interactions. All the synthesized beta-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 mu g/mL were encountered in all cases.