Monocarbonyl Analogs of Curcumin with Potential to Treat Colorectal Cancer

Clariano, Marta; Marques, Vanda; Vaz, João R.; Awam, Salma; Afonso, Marta B.; Perry, Maria de Jesus; Rodrigues, Cecília M.P.

doi:10.1002/cbdv.202300222

Cited by 10 publications

(11 citation statements)

References 42 publications

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“…Curcumin had a lipophilicity value of 3.2, which clearly indicates that curcumin falls within the moderately lipophilic range [ 37 , 38 ]. Interestingly, this reporting is in line with the experimental data previously reported by Clariano et al (2023) [ 39 ] and Shereen et al (2019) [ 40 ], who evaluated the mechanistic delivery of curcumin in humans and estimated the lipophilicity of curcumin to be in a similar range (~LogP 3.6). The synthetic derivatives 1A6 and 1B8 demonstrated a higher lipophilicity than curcumin, potentially indicating improved membrane permeability which is advantageous for drug development to enhance bioavailability.…”

Section: Discussionsupporting

confidence: 90%

Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments

Moetlediwa,

Jack,

Mazibuko-Mbeje

et al. 2024

IJMS

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Natural compounds such as curcumin, a polyphenolic compound derived from the rhizome of turmeric, have gathered remarkable scientific interest due to their diverse metabolic benefits including anti-obesity potential. However, curcumin faces challenges stemming from its unfavorable pharmacokinetic profile. To address this issue, synthetic curcumin derivatives aimed at enhancing the biological efficacy of curcumin have previously been developed. In silico modelling techniques have gained significant recognition in screening synthetic compounds as drug candidates. Therefore, the primary objective of this study was to assess the pharmacokinetic and pharmacodynamic characteristics of three synthetic derivatives of curcumin. This evaluation was conducted in comparison to curcumin, with a specific emphasis on examining their impact on adipogenesis, inflammation, and lipid metabolism as potential therapeutic targets of obesity mechanisms. In this study, predictive toxicity screening confirmed the safety of curcumin, with the curcumin derivatives demonstrating a safe profile based on their LD50 values. The synthetic curcumin derivative 1A8 exhibited inactivity across all selected toxicity endpoints. Furthermore, these compounds were deemed viable candidate drugs as they adhered to Lipinski’s rules and exhibited favorable metabolic profiles. Molecular docking studies revealed that both curcumin and its synthetic derivatives exhibited favorable binding scores, whilst molecular dynamic simulations showed stable binding with peroxisome proliferator-activated receptor gamma (PPARγ), csyclooxygenase-2 (COX2), and fatty acid synthase (FAS) proteins. The binding free energy calculations indicated that curcumin displayed potential as a strong regulator of PPARγ (−60.2 ± 0.4 kcal/mol) and FAS (−37.9 ± 0.3 kcal/mol), whereas 1A8 demonstrated robust binding affinity with COX2 (−64.9 ± 0.2 kcal/mol). In conclusion, the results from this study suggest that the three synthetic curcumin derivatives have similar molecular interactions to curcumin with selected biological targets. However, in vitro and in vivo experimental studies are recommended to validate these findings.

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Section: Discussionsupporting

confidence: 90%

Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments

Moetlediwa,

Jack,

Mazibuko-Mbeje

et al. 2024

IJMS

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“…In some methodologies, at the end of the reaction, the reaction mixture is neutralized by adding a hydrochloric acid (HCl) solution to the vessel [21] In most cases, the resulting solid is separated from the reaction mixture by vacuum filtration and washed with ice water, to remove excess base. Finally, the solid product is dried and recrystallized from hexane/ethyl acetate, EtOH, or EtOH/ to obtain pure crystals [16,[21][22][23][24]. Besides NaOH, calcium hydroxide (Ca(OH)2) has been used as a basic catalyst in CSC to obtain MKCs.…”

Section: Base-catalyzed Claisen-schmidt Condensationmentioning

confidence: 99%

“…Besides that, all the tested compounds proved to be more stable in PBS (phosphate buffer saline) with 20% acetonitrile at 37 o C for 48 h than curcumin and obeyed the 'drug-likeness properties. The authors identified MKC 26 as the most promising antitumoral compound, with an IC50 of 1.95 μM [21].…”

Section: Anticancer Activitymentioning

confidence: 99%

Monoketone Curcuminoids: An Updated Review of Their Synthesis and Biological Activities

Vieira,

Tanajura,

Heleno

et al. 2023

Preprint

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Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadien-3,5-dione], a component of Curcuma longa L. rhizomes, displays various biological and pharmacological activities. However, it is poorly bioavailable and unstable in physiological pH, which has led more stable and effective curcumin analogs (e.g., monoketone curcuminoids, or MKCs) to be synthesized, and their biological activities to be described. In this review, we cover papers published between 2019 and 2023 on the antimicrobial, anticancer, antioxidant, and antiparasitic actions as well as other less common MKC biological and pharmacological activities. We also address the Claisen-Schmidt condensation as a standard procedure to synthesize MKCs.

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“…Among different approaches, the synthesis of novel curcumin analogues by molecular modifications has exhibited similar anti-potent effects to the original curcumin molecules but with better stability and bioavailability, which are ideal for further development into novel drugs [ 42 ]. While the basic molecular structure of curcumin comprises two phenol groups connected by two α, β unsaturated carbonyl groups, a variety of curcumin analogues have been developed by modifying functional moieties, such as biaryl rings, diketone and diene chain, onto different positions of the original curcumin structure [ 36 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. With these modifications, curcumin analogues are superior to curcumin in term of pharmacokinetic properties, chemical stability and anti-cancer activities [ 46 , 52 , 53 , 54 , 55 , 56 , 57 ].…”

Section: Introductionmentioning

confidence: 99%

“…comprises two phenol groups connected by two α, β unsaturated carbonyl groups, a variety of curcumin analogues have been developed by modifying functional moieties, such as biaryl rings, diketone and diene chain, onto different positions of the original curcumin structure [36,[43][44][45][46][47][48][49][50][51]. With these modifications, curcumin analogues are superior to curcumin in term of pharmacokinetic properties, chemical stability and anti-cancer activities [46,[52][53][54][55][56][57].…”

Section: Introductionmentioning

confidence: 99%

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

Hon,

Zainal Abidin,

Abas

et al. 2024

IJMS

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Diarylpentanoids are synthesized to overcome curcumin’s poor bioavailability and low stability to show enhanced anti-cancer effects. Little is known about the anti-cancer effects of diarylpentanoid MS17 (1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in colon cancer cells. This study aimed to elucidate molecular mechanisms and pathways modulated by MS17 in colon cancer based on proteomic profiling of primary SW480 and metastatic SW620 colon cancer cells. Cytotoxicity and apoptotic effects of MS17 were investigated using MTT assay, morphological studies, and Simple Western analysis. Proteomic profiling using LC/MS analysis identified differentially expressed proteins (DEPs) in MS17-treated cells, with further analysis in protein classification, gene ontology enrichment, protein–protein interaction network and Reactome pathway analysis. MS17 had lower EC50 values (SW480: 4.10 µM; SW620: 2.50 µM) than curcumin (SW480: 17.50 µM; SW620: 13.10 µM) with a greater anti-proliferative effect. MS17 treatment of 1× EC50 induced apoptotic changes in the morphology of SW480 and SW620 cells upon 24 h treatment. A total of 24 and 92 DEPs (fold change ≥ 1.50) were identified in SW480 and SW620 cells, respectively, upon MS17 treatment of 2× EC50 for 24 h. Pathway analysis showed that MS17 may induce its anti-cancer effects in both cells via selected DEPs associated with the top enriched molecular pathways. RPL and RPS ribosomal proteins, heat shock proteins (HSPs) and ubiquitin–protein ligases (UBB and UBC) were significantly associated with cellular responses to stress in SW480 and SW620 cells. Our findings suggest that MS17 may facilitate the anti-proliferative and apoptotic activities in primary (SW480) and metastatic (SW620) human colon cancer cells via the cellular responses to stress pathway. Further investigation is essential to determine the alternative apoptotic mechanisms of MS17 that are independent of caspase-3 activity and Bcl-2 protein expression in these cells. MS17 could be a potential anti-cancer agent in primary and metastatic colon cancer cells.

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Monocarbonyl Analogs of Curcumin with Potential to Treat Colorectal Cancer

Cited by 10 publications

References 42 publications

Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments

Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments

Monoketone Curcuminoids: An Updated Review of Their Synthesis and Biological Activities

Anti-Cancer Mechanisms of Diarylpentanoid MS17 (1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one) in Human Colon Cancer Cells: A Proteomics Approach

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