Novel Pyridinium Based Ionic Liquid Promoter for Aqueous Knoevenagel Condensation: Green and Efficient Synthesis of New Derivatives with Their Anticancer Evaluation

Abstract

Herein, a distinctive dihydroxy ionic liquid ([Py-2OH]OAc) was straightforwardly assembled from the sonication of pyridine with 2-chloropropane-1,3-diol by employing sodium acetate as an ion exchanger. The efficiency of the ([Py-2OH]OAc as a promoter for the sono-synthesis of a novel library of condensed products through DABCO-catalyzed Knoevenagel condensation process of adequate active cyclic methylenes and ninhydrin was next investigated using ultimate greener conditions. All of the reactions studied went cleanly and smoothly, and the resulting Knoevenagel condensation compounds were recovered in high yields without detecting the aldol intermediates in the end products. Compared to traditional strategies, the suggested approach has numerous advantages including mild reaction conditions with no by-products, eco-friendly solvent, outstanding performance in many green metrics, and usability in gram-scale synthesis. The reusability of the ionic liquid was also studied, with an overall retrieved yield of around 97% for seven consecutive runs without any substantial reduction in the performance. The novel obtained compounds were further assessed for their in vitro antitumor potential toward three human tumor cell lines: Colo-205 (colon cancer), MCF-7 (breast cancer), and A549 (lung cancer) by employing the MTT assay, and the findings were evaluated with the reference Doxorubicin. The results demonstrated that the majority of the developed products had potent activities at very low doses. Compounds comprising rhodanine (5) or chromane (12) moieties exhibited the most promising cytotoxic effects toward three cell lines, particularly rhodanine carboxylic acid derivative (5c), showing superior cytotoxic effects against the investigated cell lines compared to the reference drug. Furthermore, automated docking simulation studies were also performed to support the results obtained.

Role and Recent Advancements of Ionic Liquids in Drug Delivery Systems

“…Even the heterocycles with nitrogen that are now employed in ILs are typically found in APIs or their precursors. Nayl et al reported the use of pyridinium-based dihydroxy ionic liquid ((Py-2OH) OAc) to improve the synthesis process and yield more potent anticancer compounds [ 90 ].…”

Ionic liquids revolutionizing biomedicine: recent advances and emerging opportunities

“…65,69 Pyridinium, ammonium, and other ILs have also been reported to have anticancer activity. 120–122 Aljuhani et al showed anticancer activities of a series of pyridinium ILs on two lung cancer cell lines (A549 and H-1229), and the maximum rate of proliferation inhibition was 99.69%. 123 Bourakadi et al evaluated the antitumor activity of a series of 3-methyl-1-alkyl-2-(thiazol-4-yl) benzimidazol-3-ium ILs against four human tumor cell lines: HT29 (colon), K652 (Leukemia), MDA-MB231, and SKBR3 (breast) and established the antitumor prospect of ILs based on thiabendazole.…”

Synthesis and Molecular Docking of Some Novel 3-Thiazolyl-Coumarins as Inhibitors of VEGFR-2 Kinase

“…In light of our previous work on the synthesis of novel antitumor heterocycles [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] and with consideration of the aforementioned results, a new sort of VEGFR-2 inhibitors has been developed as prospective anti-breast cancer agents by hybridizing the coumarin and 1,3-thiazole moieties, which have been found to inhibit kinases and have antiproliferative properties. In this study, we developed and synthesized new 3-thiazolhydrazinylcoumarins in an effort to enhance the target compounds’ synergistic pharmacological significance and assess their anti-breast cancer activity targeting VEGFR-2.…”