Anticancer Polymers via the Biginelli Reaction

Abstract

We developed a polymer-drug strategy to explore anti-cancer polymers. A series of monomers containing groups with potential anti-cancer activity have been facilely prepared through the Biginelli reaction. These monomers were used to produce water-soluble polymers through convenient radical copolymerization. The resulting polymers are biocompatible and can be directly used to suppress proliferation of different cancer cells without the release of small molecules. Theoretical calculations revealed that Biginelli groups in polymers had strong interaction with the Eg5 protein, which is highly expressed in cancer cells and is closely related to cell mitosis. Subsequent cell experiments confirmed that screened polymer is efficient in inhibiting mitosis in different cancer cells. Our study of exploring functional polymers via the combination of multicomponent reactions and theoretical calculation resulted in promising anti-cancer polymers, which might pave a path for de novo designing of functional polymers and have important implications in the fields of organic, computational, and polymer chemistry.

A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines

“…We also noticed that a handful of papers have been reported on 5-acetyl DHPMs. It appears to enrich the 5-acetyl DHPM chemistry since they too display useful activities such as, anticancer, calcium channel blocker, antiviral, anti-inflammatory, antitubercular, antioxidant and antibacterial activities [9,10,[19][20][21]. We also noticed that 5-acetyl DHPMs are conspicuously absent in many review articles and are less explored.…”

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

“…In recent years, dihydropyrimidinones (DHPMs) and their derivatives have attracted considerable attention due to the multifaceted pharmacological properties of this class of compounds [ 1 – 4 ]. The dihydropyrimidinone structure is found in calcium channel blockers [ 5 – 7 ], α1a adrenoceptor-selective antagonists [ 8 – 9 ], antihypertensive [ 10 – 13 ] and anti-inflammatory agents [ 14 – 15 ].…”

Biginelli Reaction Mediated Synthesis of Antimicrobial Pyrimidine Derivatives and Their Therapeutic Properties

“…Both reactions proved to be “key methods” for the synthesis of pyridine and pyrimidine derivatives, respectively, which were greatly developed in the following period, especially due to the applications of the synthesized compounds. The Biginelli reaction has been intensively studied in the last two decades, especially due to the applications of synthesized dihydropyrimidinone compounds at the beginning, especially as calcium channel blockers of the nifedipine-type [ 4 ], and then as antitumor [ 5 , 6 , 7 , 8 ], antibacterial, antiviral [ 9 , 10 ], anti-inflammatory [ 11 , 12 ], analgesic [ 13 ], anti-Alzheimer [ 14 ], or antioxidant [ 15 ] compounds.…”