Antiproliferative and antibacterial activity of some glutarimide derivatives

Abstract

Antiproliferative and antibacterial activities of nine glutarimide derivatives (1-9) were reported. Cytotoxicity of compounds was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay. Compound 7 (2-benzyl-2-azaspiro[5.11]heptadecane-1,3,7-trione), containing 12-membered ketone ring, was found to be the most potent toward all tested cell lines (IC 50 ¼ 9-27 mM). Preliminary screening of antibacterial activity by a disk diffusion method showed that Gram-positive bacteria were more susceptible to the tested compounds than Gram-negative bacteria. Minimum inhibitory concentration (MIC) determined by a broth microdilution method confirmed that compounds 1, 2, 4, 6-8 and 9 inhibited the growth of all tested Gram-positive and some of the Gram-negative bacteria. The best antibacterial potential was achieved with compound 9 (ethyl 4-(1-benzyl-2,6-dioxopiperidin-3-yl)butanoate) against Bacillus cereus (MIC 0.625 mg/mL; 1.97 Â 10 À3 mol/L). Distinction between more and less active/ inactive compounds was assessed from the pharmacophoric patterns obtained by molecular interaction fields.

20 Years of Forging N-Heterocycles from Acrylamides through Domino/Cascade Reactions

“…A few years later, the same team published an extension of their strategy leading to new spirocyclic domino products 6d (42-70% yield) along with evaluations of the antiproliferative and antibacterial activities of these compounds. 16 An access to other spiro congeners of 6d, again employing cyclic active methylene compounds 5d, had been independently reported previously. It is noteworthy that use of acrylamide 1 bearing a R 3 substituent at the -position resulted in the isolation of a 1:5 mixture of cis/trans stereoisomers.…”

“…Along these lines, Michael additions telescoped with an intramolecular enamide formation resembling the above studies (Schemes 5 and 6) [15][16][17][18] were investigated by various research teams, mostly motivated by structure-activity relationship (SAR) studies (Table 1). 24,25 Reaction in a basic medium with ketones 13a presumably generates in situ the corresponding enolates or enamines as precursors of the 1,4-addition products 17, the amidic nitrogen atom of which then promotes intramolecular condensation to the ketone forming an enamide.…”

A Glossary for Chemical Approaches towards Unlocking the Trove of Metabolic Treasures in Actinomycetes

“…Recently, a chlorinated analog of ARC2, named Cl-ARC, was employed to trigger the expression of CBGs in an unbiased screening regimen [ 52 ]. This resulted in the elicitation of three rare and valuable antibiotics: oxohygrolidin ( 38 ) (antifungal and insecticidal [ 55 ]) from S. ghanaensis ATCC 14672, 9-methylstreptimidone ( 39 ) (anti-inflammatory, antiproliferative and antibacterial [ 56 ]) from S. hygroscopicus ATCC 53653 and dynactin ( 40 ), as well as the known antibiotics nonactin ( 41 ), monactin ( 42 ) and trinactin ( 43 ), from WAC0256 [ 57 ]. All of them, especially dynactin, showed motility impairing potency against P. viticola, Phytophthora capsici and Aphanomyces cochlioides zoospores, which indicates non-specific activities toward peronosporomyctes ( Figure 5 ) [ 58 ].…”

Structural and vibrational analyses of new potential anticancer drug 2-(phenylmethyl)-2-azaspiro[5.11]heptadecane-1,3,7-trione

“…The most typical feature of glutarimide derivatives is that the pharmacological and spectroscopic properties can be readily modified by introduction of substituents in the glutarimide ring. Moreover, we are performing the synthesis and the properties relevant to antiproliferative and antibacterial activities of one series of glutarimide derivatives, with some newly synthesised compounds [20]. Cytotoxicity was tested toward three human cancer cell lines, HeLa, K562 and MDA-MB-453 by MTT assay.…”