Itaconic acid hybrids as potential anticancer agents

Abstract

In this paper, we report the synthesis of novel hybrids 2-14 based on itaconic acid and fluoroaniline, pyridine, indole and quinoline scaffolds. Itaconic acid is a naturally occurring compound with a Michael acceptor moiety, a key structural feature in several anticancer and antiviral drugs, responsible for the covalent binding of a drug to the cysteine residue of a specific protein. Aromatic parts of the hybrids also come from the substances reported as anticancer or antiviral agents. The synthetic route employed to access the amido-ester hybrids 2-13 used monomethyl itaconate or monomethyl itaconyl chloride and corresponding amines as the starting materials. Dimers 14 and 15 with two aminoindole or mefloquine moieties were prepared from itaconic acid and corresponding amino derivative, using standard coupling conditions (HATU/DIEA). All hybrids exerted anticancer effects in vitro against almost all the tumour cell lines that were evaluated (MCF-7, HCT 116, H460, LN-229, Capan-1, DND-41, HL-60, K-562, Z-138). Solid tumour cells were, in general, more responsive than the haematological cancer cells. The MCF-7 breast adenocarcinoma cell line appeared the most sensitive. Amido-ester 12 with chloroquine core and mefloquine homodimer 15 showed the highest activity with GI 50 values between 0.7 and 8.6 µM. In addition, compound 15 also exerted antiviral activity against Zika virus and Coxsackievirus B4 in low micromolar concentrations.

Hydroxyapatite/hyperbranched polyitaconic acid/chitosan composite scaffold for bone tissue engineering

“…70 Moreover, HAP/HBP-RAFT-PI/CS showed higher cell viability than HAP-CS and CS in the fibroblast cell line indicating the increased biocompatibility of the scaffold due to the presence of HBP-RAFT-PI, but it showed lower viability in comparison to HAP-CS scaffold on cancer cell line due to the anticancer nature of itaconic acid. 40,42 The live/dead cell assay was done on MG63 cell line due to its higher cell viability and its similarity to osteoblast cells. The cellular growth of the MG63 cells were imaged by live/dead staining assay on day 2 as illustrated in Figure 8II.…”

“…[36][37][38] Itaconic acid has huge potential for broad researchers in medicine and other industries because of its safety, biological compatibility, microbial resistance, biodegradability, chemical reactivity, and also its anticancer properties. [38][39][40][41][42] Recently, the controlled/living radical polymerization has been investigated for itaconic acid monomer and its derivatives especially by using the reversible addition-fragmentation chain transfer (RAFT) process which is considered one of the easiest and most adaptable controlled/living radical polymerization systems due to its straightforward reaction procedure, broad range of applicable monomers, and high level of controllability. [43][44][45][46][47][48] In the current publication, a modified composite scaffold hydroxyapatite/hyperbranched polyitaconic acid/ chitosan (HAP/HBP-RAFT-PI/CS) was prepared.…”

“…Itaconic acid is obtained by sugar fermentation and also from industrial waste like glycerol, making it an eco‐friendly building block for modification of natural polymers such as chitosan and also in different synthetic polymeric synthesis 36–38 . Itaconic acid has huge potential for broad researchers in medicine and other industries because of its safety, biological compatibility, microbial resistance, biodegradability, chemical reactivity, and also its anticancer properties 38–42 . Recently, the controlled/living radical polymerization has been investigated for itaconic acid monomer and its derivatives especially by using the reversible addition‐fragmentation chain transfer (RAFT) process which is considered one of the easiest and most adaptable controlled/living radical polymerization systems due to its straightforward reaction procedure, broad range of applicable monomers, and high level of controllability 43–48 …”

Recent Advances in Biotechnological Itaconic Acid Production, and Application for a Sustainable Approach

“…Several research articles present novel and multifaceted techniques for antimicrobial polymer production based on this renewable monomer, IA [ 137 , 145 , 146 , 147 ]. A proficient and effective biobased polymer was produced through radical homopolymerization and copolymerization by integrating pendant alkyne groups in the IA’s carboxylic acids structure, resulting in interactive IA derivatives.…”

“…As described previously, IA can be converted into drug-delivery systems, different hydrogels in water treatment and analyses, intelligent food packaging, antimicrobial polymers, or even in cleaning products, adhesives, coatings, thickeners, fibers, binders, lipase immobilization [ 160 ], and many other applications [ 101 ]. Additionally, IA and its derivatives have anti-inflammatory [ 161 ] antitumor [ 145 ] and antimicrobial activities [ 147 , 162 ], which could be further maneuvered therapeutically for inflammatory disorder treatment.…”