Using bioactive compounds to mitigate the formation of typical chemical contaminants generated during the thermal processing of different food matrices.

With rising consumer awareness of health and wellness, the demand for enhanced food safety is rapidly increasing. The generation of chemical contaminants during the thermal processing of food materials, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, and acrylamide happens every day in every kitchen all around the world. Unlike extraneous chemical contaminants (e.g., pesticides, herbicides, and chemical fertilizers), these endogenic chemical contaminants occur during the cooking process and cannot be removed before consumption. Therefore, much effort has been invested in searching for ways to reduce such thermally induced chemical contaminants. Recently, the addition of bioactive compounds has been found to be effective and promising. However, no systematic review of this practical science has been made yet. This review aims to summarize the latest applications of bioactive compounds for the control of chemical contaminants during food thermal processing. The underlying generation mechanisms and the toxic effects of these chemical contaminants are discussed in depth to reveal how and why they are suppressed by the addition of certain bioactive ingredients. Examples of specific bioactive compounds, such as phenolic compounds and organic acids, as well as their application scenarios, are outlined. In the end, outlooks and expectations for future development are provided based on a comprehensive summary and reflection of references.

Development of pH-Sensitive hydrogel for advanced wound Healing: Graft copolymerization of locust bean gum with acrylamide and acrylic acid.

Wounds pose a formidable challenge in healthcare, necessitating the exploration of innovative tissue-healing solutions. Traditional wound dressings exhibit drawbacks, causing tissue damage and impeding natural healing. Using a Microwave (MW)-)-assisted technique, we envisaged a novel hydrogel (Hg) scaffold to address these challenges. This hydrogel scaffold was created by synthesizing a pH-responsive crosslinked material, specifically locust bean gum-grafted-poly(acrylamide-co-acrylic acid) [LBG-g-poly(AAm-co-AAc)], to enable sustained release of c-phycocyanin (C-Pc). Synthesized LBG-g-poly(AAm-co-AAc) was fine-tuned by adjusting various synthetic parameters, including the concentration of monomers, duration of reaction, and MW irradiation intensity, to maximize the yield of crosslinked LBG grafted product and enhance encapsulation efficiency of C-Pc. Following its synthesis, LBG-g-poly(AAm-co-AAc) was thoroughly characterized using advanced techniques, like XRD, TGA, FTIR, NMR, and SEM, to analyze its structural and chemical properties. Moreover, the study examined the in-vitro C-Pc release profile from LBG-g-poly(AAm-co-AAc) based hydrogel (HgCPcLBG). Findings revealed that the maximum release of C-Pc (64.12 ± 2.69 %) was achieved at pH 7.4 over 48 h. Additionally, HgCPcLBG exhibited enhanced antioxidant performance and compatibility with blood. In vivo studies confirmed accelerated wound closure, and ELISA findings revealed reduced inflammatory markers (IL-6, IL-1ß, TNF-α) within treated skin tissue, suggesting a positive impact on injury repair. A low-cost and eco-friendly approach for creating LBG-g-poly(AAm-co-AAc) and HgCPcLBG has been developed. This method achieved sustained release of C-Pc, which could be a significant step forward in wound care technology.

Efficient and rapid digestion of proteins with a dual-enzyme microreactor featuring 3-D pores formed by dopamine/polyethyleneimine/acrylamide-coated KIT-6 molecular sieve.

The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6's large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde's spacing arm, reducing spatial hindrance and enhancing enzyme-substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.

Discovery of (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide among N-substituted cinnamamide derivatives as a novel cosmetic ingredient for hyperpigmentation.

Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but they can significantly affect human health by decreasing self-esteem. There are available only limited treatment options for hyperpigmentation disorder, among others, cosmetic products applied topically. Depigmenting ingredients were found to be ineffective and characterized by various side effects. As a result, many efforts are made to discover novel, potent, and safe melanogenesis inhibitors for possible use in topical cosmetic depigmenting formulations. Cinnamic acid derivatives constitute a widely tested group for that purpose. This article reports research in the group of N-alkyl cinnamamide derivatives (un)substituted in phenyl ring. Among tested series, (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide (compound 21) showed the most promising inhibitory properties in mushroom tyrosinase assay (IC50 = 36.98 ± 1.07 µM for monophenolase activity, IC50 = 146.71 ± 16.82 µM for diphenolase activity) and melanin production inhibition in B16F10 mouse melanoma cell line at concentration 6.25 µM resulting probably from decreasing of Tyr, Mitf, Tyrp-1, and Tyrp-2 genes expression. This compound also showed melanin production inhibitory properties in pigmented reconstructed human epidermis when used in 1 % and 2 % solutions in 50 % PEG400. In vitro evaluation of its safety profile showed no cytotoxicity to human keratinocytes HaCaT, human skin fibroblasts BJ, and human primary epidermal melanocytes HEMa, no mutagenicity in the Ames test, no genotoxicity in micronucleus test, no phototoxicity, as well as no skin irritation potential tested in PEG400 solution. This compound was also shown to penetrate across the epidermis to reach the possible site of action. The performed research led to classify (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide as a novel potential depigmenting cosmetic ingredient.

Theoretical studies on the aqueous phase and graphene heterogeneous degradation of acrylamide and acrylonitrile by HO, ClO, and BrO radicals.

The newly discovered ClO• and BrO• contribute to pollutant degradation in advanced oxidation processes, while acrylamide (AM) and acrylonitrile (ACN) are always the focus of scientists concerned due to their continuous production and highly toxic effects. Moreover, various particles with a graphene-like structure are the companions of AM/ACN in dry/wet sedimentation or aqueous phase existence, which play an important role in heterogeneous oxidation. Thus, this work focuses on the reaction mechanism and environmental effect of AM/ACN with ClO•/BrO•/HO• in the water environment under the influence of graphene (GP). The results show that although the reactivity sequence of AM and ACN takes the order of with HO• > with BrO• > with ClO•, the easiest channel always occurs at the same C-position of the two reactants. The reaction rate constants (k) of AM with three radicals are 2 times larger than that with ACN, and amide groups have a better ability to activate CC bonds than cyanide groups. The existence of GP can accelerate the target reaction, and the k increased by 9-13 orders of magnitude. The toxicity assessment results show that the toxic effect of most products is lower than that of parent compounds, but the environmental risk of products from ClO•/BrO•-adducts is higher than those from HO•-adducts. The oxidative degradation process based on ClO• and BrO• deserves special attention, and the catalytic effect of GP and its derivatives on the oxidation process is non-negligible.

Advancements in Chemical and Biosensors for Point-of-Care Detection of Acrylamide.

Acrylamide (AA), an odorless and colorless organic small-molecule compound found generally in thermally processed foods, possesses potential carcinogenic, neurotoxic, reproductive, and developmental toxicity. Compared with conventional methods for AA detection, bio/chemical sensors have attracted much interest in recent years owing to their reliability, sensitivity, selectivity, convenience, and low cost. This paper provides a comprehensive review of bio/chemical sensors utilized for the detection of AA over the past decade. Specifically, the content is concluded and systematically organized from the perspective of the sensing mechanism, state of selectivity, linear range, detection limits, and robustness. Subsequently, an analysis of the strengths and limitations of diverse analytical technologies ensues, contributing to a thorough discussion about the potential developments in point-of-care (POC) for AA detection in thermally processed foods at the conclusion of this review.

Epicatechin-Promoted Formation of Acrylamide from 3-Aminopropionamide Via Postoxidative Reaction of B-Ring.

The role of thermally generated 3-aminopropionamide as an intermediate in acrylamide formation in the Maillard reaction has been well established. Herein, the effect of epicatechin on the conversion of 3-aminopropionamide into acrylamide under oxidative conditions was investigated at 160-220 °C. Epicatechin promoted acrylamide generation and 3-aminopropionamide degradation. The stable isotope-labeling technique combined with UHPLC-Orbitrap-MS/MS analysis showed adduct formation between 3-aminopropionamide and the oxidized B ring of epicatechin to form a Schiff base. This initially formed Schiff base could directly degrade to acrylamide, undergo reduction or dehydration to other intermediates, and subsequently generate acrylamide. Based on accurate mass analysis, five intermediates with intact or dehydrated C rings were tentatively identified. Furthermore, reaction pathways were proposed that were supported by the changes in the levels of adducts formed during heating. To the authors' knowledge, this study is the first to reveal pathways through which flavanols promoted the formation of acrylamide in Maillard reactions.

Comparative effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide formation in potato chips.

This study aimed to compare the effects of pectin and hydrolyzed pectin coating as pre-frying treatments on acrylamide content and quality characteristics of fried potato chips. The hydrolyzed pectin with molecular weight (Mw) of 8.81 ± 0.49 kDa was obtained through partial degradation of pectin (Mw: 747.57 ± 6.73 kDa) using pectinase. Results showed that both pectin and hydrolyzed pectin coating significantly inhibited acrylamide formation and inhibition rates exceeded 90 %. Hydrolyzed pectin had stronger inhibitory activity against acrylamide formation than pectin, especially when the concentration of hydrolyzed pectin was >2 %, its inhibitory rate exceeded 95 %. Compared to pectin coating, hydrolyzed pectin coating endow fried potato chips with smaller browning, higher crispness, less moisture but higher oil content. Overall, hydrolyzed pectin had better application prospects than pectin in inhibiting acrylamide formation of fried potato chips.

Role of galacturonic acid in acrylamide formation: Insights from structural analysis.

Acrylamide (AA) is a neoformed compound in heated foods, mainly produced between asparagine (Asn) and glucose (Glc) during the Maillard reaction. Galacturonic acid (GalA), the major component of pectin, exhibits high activity in AA formation. This study investigated the pathway for AA formation between GalA and Asn. Three possible pathways were proposed: 1) The carbonyl group of GalA directly interacts with Asn to produce AA; 2) GalA undergoes an oxidative cleavage reaction to release α-dicarbonyl compounds, which subsequently leads to AA production; 3) 5-formyl-2-furancarboxylic acid, the thermal degradation product of GalA, reacts with Asn to generate AA. Structural analysis revealed that the COOH group in GalA accelerated intramolecular protonation and electron transfer processes, thereby increasing the formation of AA precursors such as decarboxylated Schiff base and α-dicarbonyl compounds, promoting AA formation. This study provides a theoretical basis and new insights into the formation and control of AA.

Design, Synthesis, and Antifungal Activity of Acrylamide Derivatives Containing Trifluoromethylpyridine and Piperazine.

In this study, a series of acrylamide derivatives containing trifluoromethylpyridine or piperazine fragments were rationally designed and synthesized. Subsequently, the in vitro antifungal activities of all of the synthesized compounds were evaluated. The findings revealed that compounds 6b, 6c, and 7e exhibited >80% antifungal activity against Phomopsis sp. (Ps) at the concentration of 50 µg/mL. Furthermore, the EC50 values for compounds 6b, 6c, and 7e against Ps were determined to be 4.49, 6.47, and 8.68 µg/mL, respectively, which were better than the positive control with azoxystrobin (24.83 µg/mL). At the concentration of 200 µg/mL, the protective activity of compound 6b against Ps reached 65%, which was comparable to that of azoxystrobin (60.9%). Comprehensive mechanistic studies, including morphological studies with fluorescence microscopy (FM), cytoplasmic leakage, and enzyme activity assays, indicated that compound 6b disrupts cell membrane integrity and induces the accumulation of defense enzyme activity, thereby inhibiting mycelial growth. Therefore, compound 6b serves as a valuable candidate for the development of novel fungicides for plant protection.

Rational modification of xanthan gum based on assistance of molecular dynamics simulation.

Graft copolymerization is an effective approach to improve performance of polysaccharide. However, selecting the most suitable modification strategy can be challenging due to the intricate molecular structure. Rational design through computer aided molecular dynamics (MD) simulations requires substantial computational resources. This study designed a simplified MD simulation strategy and suggested that grafting acrylamide (AM) could effectively adjust the molecular conformation of xanthan gum (XG) and its derivatives, thus regulating its viscosity and gelation properties. To rationally modify XG, a uniform experimental design was applied to tune the grafting ratios ranging from 72 % to 360 %, resulting in XG-AM solutions with viscosity ranging from 9 to 104 mPa•s at a concentration of 0.3 %. XG-AM was crosslinked by acid phenolic resin to generate gel with the viscosity of 7890 mPa·s in 3 days, which was 13 times the viscosity of unmodified XG. The controllable gelation will enhance the efficacy of XG-AM in oil recovery. By integrating rational selection of grafting strategies based on simplified MD simulation of polysaccharide derivatives and controllable grafting modification with specified grafting rates, customized production of polysaccharide derivatives can meet the requirements of a diverse range of applications.

Reactivities of acrylamide warheads toward cysteine targets: a QM/ML approach to covalent inhibitor design.

Covalent inhibition offers many advantages over non-covalent inhibition, but covalent warhead reactivity must be carefully balanced to maintain potency while avoiding unwanted side effects. While warhead reactivities are commonly measured with assays, a computational model to predict warhead reactivities could be useful for several aspects of the covalent inhibitor design process. Studies have shown correlations between covalent warhead reactivities and quantum mechanic (QM) properties that describe important aspects of the covalent reaction mechanism. However, the models from these studies are often linear regression equations and can have limitations associated with their usage. Applications of machine learning (ML) models to predict covalent warhead reactivities with QM descriptors are not extensively seen in the literature. This study uses QM descriptors, calculated at different levels of theory, to train ML models to predict reactivities of covalent acrylamide warheads. The QM/ML models are compared with linear regression models built upon the same QM descriptors and with ML models trained on structure-based features like Morgan fingerprints and RDKit descriptors. Experiments show that the QM/ML models outperform the linear regression models and the structure-based ML models, and literature test sets demonstrate the power of the QM/ML models to predict reactivities of unseen acrylamide warhead scaffolds. Ultimately, these QM/ML models are effective, computationally feasible tools that can expedite the design of new covalent inhibitors.

A Mass Spectrometry Strategy for Protein Quantification Based on the Differential Alkylation of Cysteines Using Iodoacetamide and Acrylamide.

Mass spectrometry has become the most prominent yet evolving technology in quantitative proteomics. Today, a number of label-free and label-based approaches are available for the relative and absolute quantification of proteins and peptides. However, the label-based methods rely solely on the employment of stable isotopes, which are expensive and often limited in availability. Here we propose a label-based quantification strategy, where the mass difference is identified by the differential alkylation of cysteines using iodoacetamide and acrylamide. The alkylation reactions were performed under identical experimental conditions; therefore, the method can be easily integrated into standard proteomic workflows. Using high-resolution mass spectrometry, the feasibility of this approach was assessed with a set of tryptic peptides of human serum albumin. Several critical questions, such as the efficiency of labeling and the effect of the differential alkylation on the peptide retention and fragmentation, were addressed. The concentration of the quality control samples calculated against the calibration curves were within the ±20% acceptance range. It was also demonstrated that heavy labeled peptides exhibit a similar extraction recovery and matrix effect to light ones. Consequently, the approach presented here may be a viable and cost-effective alternative of stable isotope labeling strategies for the quantification of cysteine-containing proteins.

The antibacterial and antialgal enhancement of the hydroquinone acrylamide polyurethane coating based on microphase separation.

The undesirable and inevitable adhesion of marine organisms on submerged surfaces has seriously affect the environment, economy and society, so emerging and promising strategies for antifouling are required. Here, the novel and environmental strategy of the antibacterial and antialgal materials was proposed for the application of the antifouling coating without releasing harmful substances. The environment-friendly antifouling agent, the capsaicin derivative N-(2,5-dihydroxy-4-acrylamide meth-ylbenzyl)acrylamide (PHABA), was modified to the molecular chain of the polyurethane. The best tensile strength was up to 23.5 MPa of PUP-25% and the elongation at break was 415% of PUP-25%. The excellent wear resistance (300 wear cycles) and chemical solution resistance (H2SO4, NaOH, and NaCl solutions) revealed the applicability of the coating. PHABA would migrate to the surface of the polyurethane coating with time and enhanced the antibacterial and antialgal properties of the coating. PUP-25% prevented more than 90% of bacterial and algal adhesion, indicating the potential application of the antifouling coating.

Acrylamide in food products and the role of electrochemical biosensors in its detection: a comprehensive review.

In this review, the mechanisms of acrylamide formation in food, along with aspects related to its toxicity and associated consumption risks, are investigated, highlighting the potential impact on human health. European regulations regarding acrylamide content in food products are also addressed, emphasizing the importance of monitoring and detecting this substance in nutrition, by public health protection measures. The primary objective of the research is to explore and analyze innovative methods for detecting acrylamide in food, with a particular focus on electrochemical biosensors. This research direction is motivated by the need to develop rapid, sensitive, and efficient monitoring techniques for this toxic compound in food products, considering the associated consumption risks. The research has revealed several significant results. Studies have shown that electrochemical biosensors based on hemoglobin exhibited increased sensitivity and low detection limits, capable of detecting very low concentrations of acrylamide in processed foods. Additionally, it has been found that the use of functionalized nanomaterials, such as carbon nanotubes and gold nanoparticles, has led to the improvement of electrochemical biosensor performance in acrylamide detection. The integration of these technological innovations and functionalization strategies has enhanced the sensitivity, specificity, and stability of biosensors in measuring acrylamides. Thus, the results of this research offer promising perspectives for the development of precise and efficient methods for monitoring acrylamides in food, contributing to the improvement of food quality control and the protection of consumer health.

Inhibition of polyphenols on Maillard reaction products and their induction of related diseases: A comprehensive review.

BACKGROUND: Food products undergo a pronounced Maillard reaction (MR) during the cooking process, leading to the generation of substantial quantities of Maillard reaction products (MRPs). Within this category, advanced glycation end products (AGEs), acrylamide (AA), and heterocyclic amines (HAs) have been implicated as potential risk factors associated with the development of diseases. PURPOSE: To explore the effects of polyphenols, a class of bioactive compounds found in plants, on the inhibition of MRPs and related diseases. Previous research has mainly focused on their interactions with proteins and their effects on the gastrointestinal tract and other diseases, while fewer studies have examined their inhibitory effects on MRPs. The aim is to offer a scientific reference for future research investigating the inhibitory role of polyphenols in the MR. METHODS: The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research. RESULTS: Polyphenols have the potential to inhibit the formation of harmful MRPs and prevent related diseases. The inhibition of MRPs by polyphenols primarily occurs through the following mechanisms: trapping α-dicarbonyl compounds, scavenging free radicals, chelating metal ions, and preserving protein structure. Simultaneously, polyphenols exhibit the ability to impede the onset and progression of related diseases such as diabetes, atherosclerosis, cancer, and Alzheimer's disease through diverse pathways. CONCLUSION: This review presents that inhibition of polyphenols on Maillard reaction products and their induction of related diseases. Further research is imperative to enhance our comprehension of additional pathways affected by polyphenols and to fully uncover their potential application value in inhibiting MRPs.

Synthesis, characterization and column adsorption properties of gum ghatti and water hyacianth derived cellulose grafted poly(vinyl sulfonic acid-co-acrylamide) composites.

Vinylsulfonic acid (VSA), acrylamide (AM) and N, N methylene bis acrylamide(MBA) were copolymerized by radical polymerization in the presence of gum ghatti (GG) and treated water hyacianth (WH) in water. Several composite copolymers were prepared by varying the i) AM: VSA molar ratios ii) wt% of GG and iii) wt% of treated WH based on a Box-Behnken Design(BBD) of a response surface methodology (RSM) model with three input variables and the batch adsorption capacity (mg/g) of 100 mg/L Cd (II) from water as response. The composite polymer was characterized by Fourier transform Infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis(TGA), X- ray photo electron spectroscopy (XPS), compressive strength, pH reversibility, pH at point zero charge (pHPZC), Brunauer-Emmett-Teller (BET) surface area and scanning electron microscopy (SEM). The network parameters of the composites were determined. The copolymer composite prepared with AM: VSA of 5:1 containing 10 wt% GG and 4 wt% treated WH showed an optimum batch adsorption capacity of 399.15 mg/g Cd (II) from water containing 100 mg/L Cd (II). The same composite showed an adsorption capacity of 170.1 mg/g and a removal% of 31.5 at a feed concentration/feed flow rate/bed height of 150 mgL-1/30mLmin-1/30 mm in a fixed bed column.

Acrylamide in heat-treated carbohydrate-rich foods in Turkey.

This study was conducted to provide data on the amount of acrylamide (AA) in 270 heat-treated carbohydrate-rich foods in Turkey, determined by gas chromatography-mass spectrometry (GC-MS). A total of 270 samples were analysed and it was found that 85% of potato chips, 80% of biscuits, 85% of cakes, 80% of bread, 80% of roasted peanuts, 80% of roasted nuts and 85% of pretzels contained AA above the limit of quantification (LOQ). Analytical results indicated that 10 corn chips samples, 4 biscuits samples, all bread samples, all wheat bread samples, 2 dried bread samples and 1 pretzel sample contained AA levels above the benchmark levels of 150, 350, 50, 50, 300 and 300 µg/kg, respectively, as set by the European Commission.

Preparation of xyloglucan-grafted poly(N-hydroxyethyl acrylamide) copolymer by free-radical polymerization for in vitro evaluation of human dermal fibroblasts.

Xyloglucan is a rigid polysaccharide that belongs to the carbohydrate family. This hemicellulose compound has been widely used in biomedical research because of its pseudoplastic, mucoadhesive, mucomimetic, and biocompatibility properties. Xyloglucan is a polyose with no amino groups in its structure, which also limits its range of applications. It is still unknown whether grafting hydrophilic monomers onto xyloglucan can produce derivatives that overcome these shortcomings. This work aimed to prepare the first copolymers in which N-hydroxyethyl acrylamide is grafted onto tamarind xyloglucan by free-radical polymerization. The biocompatibility of these structures in vitro was evaluated using human dermal fibroblasts. Gamma radiation-induced graft polymerization was employed as an initiator by varying the radiation dose from 5-25 kGy. The structure of the graft copolymer, Xy-g-poly(N-hydroxyethyl acrylamide), was verified by thermal analysis, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. The findings indicate that the degree of grafting and the cytotoxicity/viability of the xyloglucan-based copolymer were independent of dose. Notably, the grafted galactoxyloglucan exhibited efficient support for human dermal fibroblasts, showing heightened proliferative capacity and superior migration capabilities compared to the unmodified polymer. This copolymer might have the potential to be used in skin tissue engineering.

Research progress on small molecule inhibitors targeting KRAS G12C with acrylamide structure and the strategies for solving KRAS inhibitor resistance.

KRAS (Kirsten-RAS) is a highly mutated gene in the RAS (rat sarcoma) gene family that acts as a critical switch in intracellular signaling pathways, regulating cell proliferation, differentiation, and survival. The continuous activation of KRAS protein resulting from mutations leads to the activation of multiple downstream signaling pathways, inducing the development of malignant tumors. Despite the significant role of KRAS in tumorigenesis, targeted drugs against KRAS gene mutations have failed, and KRAS was once considered an undruggable target. The development of KRAS G12C mutant conformational modulators and the introduction of Sotorasib (R&D code: AMG510) have been a breakthrough in this field, with its remarkable clinical outcomes. Consequently, there is now a great number of KRAS G12C mutations. Patent applications for mutant GTPase KRAS G12C inhibitors, which are said to be covalently modified by cysteine codon 12, have been submitted since 2014. This review classifies KRAS G12C inhibitors based on their chemical structure and evaluates their biological properties. Additionally, it discusses the obstacles encountered in KRAS inhibitor research and the corresponding solutions.