Two Important Anticancer Mechanisms of Natural and Synthetic Chalcones

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Oct 14

PMID 36232899

Authors

Teodora Constantinescu

Alin Grig Mihis

Affiliations

Soon will be listed here.

Abstract

ATP-binding cassette subfamily G and tubulin pharmacological mechanisms decrease the effectiveness of anticancer drugs by modulating drug absorption and by creating tubulin assembly through polymerization. A series of natural and synthetic chalcones have been reported to have very good anticancer activity, with a half-maximal inhibitory concentration lower than 1 µM. By modulation, it is observed in case of the first mechanism that methoxy substituents on the aromatic cycle of acetophenone residue and substitution of phenyl nucleus by a heterocycle and by methoxy or hydroxyl groups have a positive impact. To inhibit tubulin, compounds bind to colchicine binding site. Presence of methoxy groups, amino groups or heterocyclic substituents increase activity.

Citing Articles

Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites.

Viperino A, Hopfner M, Edel N, Al Nasr I, Koko W, Khan T Pharmaceuticals (Basel). 2025; 18(1).

PMID: 39861113 PMC: 11768771. DOI: 10.3390/ph18010050.

()-2-Benzylidenecyclanones: Part XX-Reaction of Cyclic Chalcone Analogs with Cellular Thiols: Unexpected Increased Reactivity of 4-Chromanone- Compared to 1-Tetralone Analogs in Thia-Michael Reactions.

Bognar G, Kenari F, Pinter Z, Borges I, Camargo A, Oliveira H Molecules. 2024; 29(23).

PMID: 39683654 PMC: 11643487. DOI: 10.3390/molecules29235493.

()-2-Benzylidenecyclanones: Part XIX. Reaction of ()-2-(4'-X-Benzylidene)-1-tetralones with Cellular Thiols: Comparison of Thiol Reactivities of Open-Chain Chalcones and Their Six- and Seven-Membered Cyclic Analogs.

Kenari F, Pinter Z, Molnar S, Borges I, Camargo A, Napolitano H Int J Mol Sci. 2024; 25(14).

PMID: 39063017 PMC: 11277078. DOI: 10.3390/ijms25147773.

Synthesis, anticancer evaluation of novel hybrid pyrazole-based chalcones, molecular docking, DNA fragmentation, and gene expression: studies.

Yasser N, Sroor F, El-Shorbagy H, Eissa S, Hassaneen H, Abdelhamid I RSC Adv. 2024; 14(30):21859-21873.

PMID: 38984258 PMC: 11232109. DOI: 10.1039/d4ra03375b.

Exploring Thiazolopyridine AV25R: Unraveling of Biological Activities, Selective Anti-Cancer Properties and In Silico Target and Binding Prediction in Hematological Neoplasms.

Ladwig A, Gupta S, Ehlers P, Sekora A, Alammar M, Koczan D Molecules. 2023; 28(24).

PMID: 38138609 PMC: 10745743. DOI: 10.3390/molecules28248120.

References

Turijan-Espinoza E, Ruiz-Rodriguez V, Uresti-Rivera E, Martinez-Leija E, Zermeno-Nava J, Guel-Panola A . Clinical utility of ABCB1 and ABCG2 genotyping for assessing the clinical and pathological response to FAC therapy in Mexican breast cancer patients. Cancer Chemother Pharmacol. 2021; 87(6):843-853. DOI: 10.1007/s00280-021-04244-y. View

Zhang Y, Wen Z, Wan K, Yuan D, Zeng X, Liang G . A novel synthesized 3', 5'-diprenylated chalcone mediates the proliferation of human leukemia cells by regulating apoptosis and autophagy pathways. Biomed Pharmacother. 2018; 106:794-804. DOI: 10.1016/j.biopha.2018.06.153. View

Taylor N, Manolaridis I, Jackson S, Kowal J, Stahlberg H, Locher K . Structure of the human multidrug transporter ABCG2. Nature. 2017; 546(7659):504-509. DOI: 10.1038/nature22345. View

Du S, Sarver J, Trabbic C, Erhardt P, Schroering A, Maltese W . 6-MOMIPP, a novel brain-penetrant anti-mitotic indolyl-chalcone, inhibits glioblastoma growth and viability. Cancer Chemother Pharmacol. 2018; 83(2):237-254. PMC: 6645365. DOI: 10.1007/s00280-018-3726-1. View

Seitz T, Hackl C, Freese K, Dietrich P, Mahli A, Thasler R . Xanthohumol, a Prenylated Chalcone Derived from Hops, Inhibits Growth and Metastasis of Melanoma Cells. Cancers (Basel). 2021; 13(3). PMC: 7866261. DOI: 10.3390/cancers13030511. View

Pena-Solorzano D, Stark S, Konig B, Sierra C, Ochoa-Puentes C . ABCG2/BCRP: Specific and Nonspecific Modulators. Med Res Rev. 2016; 37(5):987-1050. DOI: 10.1002/med.21428. View

Guazelli C, Fattori V, R Ferraz C, Borghi S, Casagrande R, Baracat M . Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis. Chem Biol Interact. 2020; 333:109315. DOI: 10.1016/j.cbi.2020.109315. View

Tay R, Richardson E, Toh H . Revisiting the role of CD4 T cells in cancer immunotherapy-new insights into old paradigms. Cancer Gene Ther. 2020; 28(1-2):5-17. PMC: 7886651. DOI: 10.1038/s41417-020-0183-x. View

Zeng Z, Zhang C, Li J, Cui D, Jiang Y, Pu K . Activatable Polymer Nanoenzymes for Photodynamic Immunometabolic Cancer Therapy. Adv Mater. 2020; 33(4):e2007247. DOI: 10.1002/adma.202007247. View

10.

Bonandi E, Foschi F, Marucci C, Dapiaggi F, Sironi M, Pieraccini S . Synthesis of Thicolchicine-Based Conjugates: Investigation towards Bivalent Tubulin/Microtubules Binders. Chempluschem. 2020; 84(1):98-102. DOI: 10.1002/cplu.201800497. View

11.

Liu S, Jiang Q, Zhao X, Zhao R, Wang Y, Wang Y . A DNA nanodevice-based vaccine for cancer immunotherapy. Nat Mater. 2020; 20(3):421-430. DOI: 10.1038/s41563-020-0793-6. View

12.

Sabnis A, Bivona T . Principles of Resistance to Targeted Cancer Therapy: Lessons from Basic and Translational Cancer Biology. Trends Mol Med. 2019; 25(3):185-197. PMC: 6401263. DOI: 10.1016/j.molmed.2018.12.009. View

13.

Jackson S, Manolaridis I, Kowal J, Zechner M, Taylor N, Bause M . Structural basis of small-molecule inhibition of human multidrug transporter ABCG2. Nat Struct Mol Biol. 2018; 25(4):333-340. DOI: 10.1038/s41594-018-0049-1. View

14.

Eren E, Watts N, Sackett D, Wingfield P . Conformational changes in tubulin upon binding cryptophycin-52 reveal its mechanism of action. J Biol Chem. 2021; 297(4):101138. PMC: 8456064. DOI: 10.1016/j.jbc.2021.101138. View

15.

Gomes M, Braga R, Grzelak E, Neves B, Muratov E, Ma R . QSAR-driven design, synthesis and discovery of potent chalcone derivatives with antitubercular activity. Eur J Med Chem. 2017; 137:126-138. PMC: 6031314. DOI: 10.1016/j.ejmech.2017.05.026. View

16.

Khan I, Garikapati K, Shaik A, Makani V, Rahim A, Shareef M . Design, synthesis and biological evaluation of 1, 4-dihydro indeno[1,2-c] pyrazole linked oxindole analogues as potential anticancer agents targeting tubulin and inducing p53 dependent apoptosis. Eur J Med Chem. 2017; 144:104-115. DOI: 10.1016/j.ejmech.2017.12.010. View

17.

Hu Y, Hu C, Pan G, Yu C, Ansari M, Bheemanaboina R . Novel chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids as potential antibacterial repressors against methicillin-resistant Staphylococcus aureus. Eur J Med Chem. 2021; 222:113628. DOI: 10.1016/j.ejmech.2021.113628. View

18.

Sultana F, Bonam S, Reddy V, Nayak V, Akunuri R, Routhu S . Synthesis of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates as microtubule targeting and apoptosis inducing agents. Bioorg Chem. 2017; 76:1-12. DOI: 10.1016/j.bioorg.2017.10.019. View

19.

Raj S, Khurana S, Choudhari R, Kesari K, Kamal M, Garg N . Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy. Semin Cancer Biol. 2019; 69:166-177. DOI: 10.1016/j.semcancer.2019.11.002. View

20.

Tuli H, Mittal S, Aggarwal D, Parashar G, Parashar N, Upadhyay S . Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance. Semin Cancer Biol. 2020; 73:196-218. DOI: 10.1016/j.semcancer.2020.09.014. View