Aplysinopsin analogs: Synthesis and anti-proliferative activity of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-diones

Abstract

A series of substituted (Z)-5-(N-benzylindol-3-ylmethylene)imidazolidine-2,4-dione (3) analogs structurally related to aplysinopsin, and that incorporate a variety of substituents in both the indole and N-benzyl moieties have been synthesized under microwave irradiation and conventional heating methods These analogs were evaluated for their anti-proliferative activity against MCF-7 and MDA-231 breast cancer cell lines, and A549 and H460 lung cancer cell lines. Two analogs, 3f and 3j had IC50 values of 4.4 and 5.2 μM, respectively, compared to 5-fluorouracil (IC50 = 15.2 μM) against MCF-7 cells.

Ninhydrin in synthesis of heterocyclic compounds

“…[254][255][256][257] Additionally, imidazolidines have attracted considerable attention from synthetic organic chemists since these scaffolds exhibit significant pharmacological properties. [258][259][260] The reaction of ninhydrin with urea was first reported by Van Slyke and Hamilton in 1941, 261 and two years later, they reported the formation of a stable ninhydrin-urea compound. 262 Recently, nineteen new spirohydantoins were synthesized in three steps, outlined in Scheme 54: the ureas not …”

An Overview of Aplysinopsins: Synthesis and Biological Activities

“…The preparation of an N -benzyl-1 H -indoles to be N -benzyl aplysinopsin analogs was of interest to a group of researchers as potential anticancer agents. In 2010, they reported a series of substituted ( Z )-5-( N -benzylindol-3-ylmethylene)imidazolidine-2,4-dione analogs 54 using microwave irradiation and conventional heating methods ( Scheme 8 ) [ 23 ].…”

“…Several of these analogs showed potent growth inhibition against melanoma UACC-257, OVCAR-8 ovarian, and MCF-7 breast cancer cells besides significant cytotoxicity. Therefore, these analogs could be regarded as useful lead compounds for further structural optimization as antitumor agents [ 22 , 23 ].…”

“…Recently, it has been shown that aplysinopsins act as a blood–brain barrier permeable scaffold for anti-cholinesterase and anti-BACE-1 activity (beta-site amyloid-precursor protein-cleaving enzyme 1) [ 21 ]. Additionally, aplysinopsin and its derivatives were found to possess significant anticancer activity against several cancer cell lines, including multidrug resistance (MDR) cell lines, leukemia, and breast, colon, and uterine cancer cell lines [ 22 , 23 ]. This review gives an up-to-date overview of marine alkaloid aplysinopsins: their origin, isolation sources, synthesis, analogs, and bioactivity.…”

Recent Advances in the Synthesis of Hydantoins: The State of the Art of a Valuable Scaffold

“…Microwave-induced reactions were also reported, , and Thirupathi Reddy et al showed the tremendous advantage of this technology on the condensation reaction, comparing classical heating and microwave conditions that reduced the reaction times from hours to seconds while improving the yields . The solvent-free, microwave-assisted, boric acid-catalyzed condensation of 4-methoxybenzaldehyde with (thio)­hydantoin was also reported, leading to the corresponding benzilidene (thio)­hydantoin in moderate to good yields .…”