SavedAdd your journal

Journals / Yenilikçi Mühendislik ve Doğa Bilimleri / 2026 / Volume: 6 Issue: 2

Chalcones as versatile scaffolds in drug design: synthesis, structure–activity relationship (sar), and anticancer potential

İlaç tasarımında çok yönlü iskelet yapılar olarak kalkonlar: sentez, yapı-aktivite ilişkisi (SAR) ve antikanser potansiyeli

Nurcan Berber(ÇANAKKALE ONSEKİZ MART ÜNİVERSİTESİ)0000-0002-1595-585X
Pages
—
Publication Date
2026-07-30
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Finally, current synthetic and translational challenges, together with emerging strategies such as hybrid molecule design, prodrug approaches, computational SAR analysis, and bioisosteric modification, are outlined to guide the development of next generation chalcone based anticancer agents.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Chalcones, 1,3-diaryl-2-propen-1-ones, represent a structurally simple yet highly versatile class of α, β-unsaturated carbonyl compounds that have gained considerable attention in anticancer drug discovery.
📊
Key Findings & Data:The persistent emergence of drug resistance, off target toxicity, and tumor heterogeneity drives the search for tunable, multi target scaffolds, and chalcones occupy a privileged position by engaging multiple cancer-related macromolecular targets.
💡
Conclusion & Impact:Finally, current synthetic and translational challenges, together with emerging strategies such as hybrid molecule design, prodrug approaches, computational SAR analysis, and bioisosteric modification, are outlined to guide the development of next generation chalcone based anticancer agents.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Chalcone · Anticancer agents · Claisen–Schmidt condensation

Abstract

Chalcones, 1,3-diaryl-2-propen-1-ones, represent a structurally simple yet highly versatile class of α, β-unsaturated carbonyl compounds that have gained considerable attention in anticancer drug discovery. The persistent emergence of drug resistance, off target toxicity, and tumor heterogeneity drives the search for tunable, multi target scaffolds, and chalcones occupy a privileged position by engaging multiple cancer-related macromolecular targets. Their modular architecture allows efficient structural diversification through well-established synthetic methodologies, most notably the Claisen–Schmidt condensation. Systematic variation of substituents on either aromatic ring provides a convenient platform for structure activity relationship (SAR) studies, enabling fine-tuning of electronic properties, molecular planarity, and physicochemical characteristics. This review highlights recent advances in the synthesis and SAR driven optimization of chalcone derivatives with anticancer activity. Particular attention is given to how substituents on rings A and B translate into changes in potency and target selectivity across breast, lung, colorectal, cervical, prostate, and hematological malignancies, supported by a comparative table linking structural features to in vitro IC₅₀ values and mechanism of action. Key synthetic considerations, including substituent effects, accessibility of sterically and electronically diverse systems, green chemistry-oriented variants of the Claisen–Schmidt condensation, and opportunities for scaffold modification, are discussed. In parallel, selected biological mechanisms such as tubulin disruption, kinase modulation, apoptosis induction, redox regulation, and antiangiogenic effects are briefly systematically summarized to contextualize structure function relationships. Finally, current synthetic and translational challenges, together with emerging strategies such as hybrid molecule design, prodrug approaches, computational SAR analysis, and bioisosteric modification, are outlined to guide the development of next generation chalcone based anticancer agents.

Özet

Kalkonlar, yapısal olarak basit ancak yüksek derecede çok yönlü α,β-doymamış karbonil bileşikleri sınıfını temsil etmekte olup, antikanser ilaç keşfi alanında önemli ölçüde ilgi görmektedir. Modüler yapıları, özellikle Claisen–Schmidt kondenzasyonu başta olmak üzere iyi tanımlanmış sentez yöntemleri aracılığıyla etkin bir yapısal çeşitlendirmeye olanak tanımaktadır. Her iki aromatik halka üzerindeki sübstitüentlerin sistematik olarak değiştirilmesi, elektronik özelliklerin, moleküler planarlığın ve fizikokimyasal karakteristiklerin ince ayarlanmasını mümkün kılarak, yapı–aktivite ilişkisi (SAR) çalışmalarına elverişli bir platform sunmaktadır. Bu derleme, antikanser aktiviteye sahip kalkon türevlerinin sentezi ve SAR temelli optimizasyonuna ilişkin güncel gelişmeleri ele almaktadır. Sübstitüent etkileri, sterik ve elektronik açıdan çeşitli sistemlerin erişilebilirliği ile iskelet (scaffold) modifikasyonuna yönelik olanaklar dâhil olmak üzere temel sentetik hususlar tartışılmaktadır. Buna paralel olarak, yapı–fonksiyon ilişkilerinin bağlamlandırılması amacıyla tübülin bozulması, kinaz modülasyonu, apoptoz indüksiyonu ve antianjiyojenik etkiler gibi seçilmiş biyolojik mekanizmalar kısaca özetlenmektedir. Son olarak, kalkon temelli yeni nesil antikanser ajanların geliştirilmesine yön vermek amacıyla mevcut sentetik ve translasyonel zorluklar ile hibrit molekül tasarımı ve biyoizosterik modifikasyon gibi ortaya çıkan stratejiler ele alınmaktadır.

🔖

Cite This Article

Berber, N. (2026). Chalcones as versatile scaffolds in drug design: synthesis, structure–activity relationship (sar), and anticancer potential. Yenilikçi Mühendislik ve Doğa Bilimleri, Volume: 6 Issue: 2. https://doi.org/10.61112/jiens.1851347

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (98)

  1. Wang S, Liu Y, Feng, Y, Zhan J, Swinnen J, Li Y, Ni Y (2019) A review on curability of cancers: more efforts for novel therapeutic options are needed. Cancers 11:1782. https://doi.org/10.3390/cancers11111782
  2. Li J, Chen F, Cona MM et al (2012) A review on various targeted anticancer therapies. Targ Oncol 7:69-85. https://doi.org/10.1007/s11523-012-0212-2
  3. Giordano S, Petrelli A (2008) From single-to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. Curr Med Chem 15:422-432. https://doi.org/10.2174/092986708783503212
  4. Szumilak M, Wiktorowska-Owczarek A, Stanczak A (2021) Hybrid drugs—a strategy for overcoming anticancer drug resistance?. Molecules 26:2601. https://doi.org/10.3390/molecules26092601
  5. Doostmohammadi A, Jooya H, Ghorbanian K, Gohari S, Dadashpour M (2024) Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents. Cell Commun Signal 22:228. https://doi.org/10.1186/s12964-024-01607-9
  6. Ni Y, Zhou X, Yang J, Shi H, Li H, Zhao X, Ma X (2021) The role of tumor-stroma interactions in drug resistance within tumor microenvironment. Front Cell Dev Biol 9:637675. https://doi.org/10.3389/fcell.2021.637675
  7. Min HY, Lee HY (2022) Molecular targeted therapy for anticancer treatment. Exp Mol Med 54:1670-1694. https://doi.org/10.1038/s12276-022-00864-3
  8. World Health Organization. "Cancer". https://gco.iarc.fr/tomorrow/en/dataviz/isotype, Accessed 18 August 2024.
  9. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74:229-263. https://doi.org/10.3322/caac.21834
  10. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) "Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries". CA Cancer J Clin 71:209–49. https://doi.org/10.3322/caac.21660
  11. Liu B, Zhou H, Tan L, Siu KTH, Guan XY (2024) Exploring treatment options in cancer: tumor treatment strategies. Signal Transduct Target Ther, 9:175. https://doi.org/10.1038/s41392-024-01856-7
  12. Garg P, Malhotra J, Kulkarni P, Horne D, Salgia R, Singhal S S (2024) Emerging therapeutic strategies to overcome drug resistance in cancer cells. Cancers 16:2478. https://doi.org/10.3390/cancers16132478
  13. Goyal K, Kaur R, Goyal A, Awasthi R (2021) Chalcones: A review on synthesis and pharmacological activities. J Appl Pharm Sci 11:001-014. https://doi.org/10.7324/JAPS.2021.11s101
  14. Talevi A (2015) Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective. Front Pharmacol 6:205. https://doi.org/10.3389/fphar.2015.00205
  15. Singh P, Anand A, Kumar V (2014) Recent developments in biological activities of chalcones: A mini review. Eur J Med Chem 85:758-777. https://doi.org/10.1016/j.ejmech.2014.08.033
  16. Sashidhara KV, Avula SR, Mishra V, Palnati GR, Singh LR, Singh N et al (2015) Identification of quinoline–chalcone hybrids as potential antiulcer agents. Eur J Med Chem 89:638-653. https://doi.org/10.1016/j.ejmech.2014.10.068
  17. Rudrapal M, Khan J, Dukhyil AAB, Alarousy RMII, Attah, EI, Sharma, T et al (2021) Chalcone scaffolds, bioprecursors of flavonoids: Chemistry, bioactivities, and pharmacokinetics. Molecules 26:7177. https://doi.org/10.3390/molecules26237177
  18. Jasim HA, Nahar L, Jasim MA, Moore SA, Ritchie KJ, Sarker SD (2021) Chalcones: Synthetic chemistry follows where nature leads. Biomolecules 11:1203. https://doi.org/10.3390/biom11081203
  19. Elkanzi NA, Hrichi H, Alolayan RA, Derafa W, Zahou FM, Bakr RB (2022) Synthesis of chalcones derivatives and their biological activities: a review. ACS omega 7:27769-27786. https://doi.org/10.1021/acsomega.2c01779
  20. Gomes MN, Muratov EN, Pereira M, Peixoto JC, Rosseto LP, Cravo PV et al (2017) Chalcone derivatives: promising starting points for drug design. Molecules 22:1210. https://doi.org/10.3390/molecules22081210
  21. Marotta L, Rossi S, Ibba R, Brogi S, Calderone V, Butini S, et al (2022) The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery. Front Chem 10:988376. https://doi.org/10.3389/fchem.2022.988376
  22. Alshazly O, Abuo-Rahma GEDA, Mohamed MF, Abdel-Aziz M (2025) Amide linked chalcone derivatives, a promising class of compounds with versatile biological effects. RSC advances 15:19043-19068. https://doi.org/10.1039/D5RA00834D
  23. Elshamsy AM, Mustafa M, Nocentini A, Massardi ML, Ali TF, Rabea SM et al (2025) Design, synthesis, and in vitro anticancer evaluation of thiazole-based chalcones linked to sulfanilamide as tumor-associated carbonic anhydrase IX and XII inhibitors. J Med Chem 68:15151-15164. https://doi.org/10.1021/acs.jmedchem.5c01392
  24. Shakir SM, Mohsen AM, Ahmed SG, Al-Majedy YK, Ibraheem HH, Issa AA et al (2025) Synthesis of Chalcone Mediated Novel Pyrazoline ((3-Aminophenyl)-4, 5-Dihydro-1H-Pyrazole-1-yl Ethanone Derivative) Scaffolds: DFT Study, Insilico Predictions, and Anticancer Activity. Plasmonics 1-13. https://doi.org/10.1007/s11468-025-02988-4
  25. Go ML, Wu X, Liu XL (2005) Chalcones: an update on cytotoxic and chemoprotective properties. Curr Med Chem 12:483-499. https://doi.org/10.2174/0929867053363153
  26. Karthikeyan C, Moorthy NS, Ramasamy S, Vanam U, Manivannan E, Karunagaran D, Trivedi P (2015) Advances in chalcones with anticancer activities. Recent Pat Anticancer Drug Discov 10:97-115. https://doi.org/10.2174/1574892809666140819153902
  27. Mphahlele MJ, Maluleka MM, Parbhoo N, Malindisa ST (2018) Synthesis, evaluation for cytotoxicity and molecular docking studies of benzo[c]furan-chalcones for potential to inhibit tubulin polymerization and/or EGFR-tyrosine kinase phosphorylation. Int J Mol Sci 19: 2552. https://doi.org/10.3390/ijms19092552
  28. Zhang S, Tang X, Wang M, Hou T (2024) Machine learning for drug design: a review. Drug Discov Today 29: 103802. https://doi.org/10.1016/j.drudis.2023.103802
  29. Chowdhary S, Preeti S, Gupta N, Kumar R, Kumar V (2024) Advances in chalcone-based anticancer therapy: Mechanisms, preclinical advances, and future perspectives. Expert Opin Drug Discov 19:1417-1437. https://doi.org/10.1080/17460441.2024.2436908
  30. Constantinescu T, Lungu CN (2021) Anticancer activity of natural and synthetic chalcones. Int J Mol Sci 22:11306. https://doi.org/10.3390/ijms222111306
  31. Leite FF, de Sousa NF, de Oliveira BHM, Duarte GD, Ferreira MDL et al (2023) Anticancer activity of chalcones and its derivatives: review and in silico studies. Molecules 28:4009. https://doi.org/10.3390/molecules28104009
  32. Villa SM, Heckman J, Bandyopadhyay D (2024) Medicinally privileged natural chalcones: abundance, mechanisms of action, and clinical trials. Int J Mol Sci 25:9623. https://doi.org/10.3390/ijms25179623
  33. Shalaby MA, Rizk SA, Fahim AM (2023) Synthesis, reactions and application of chalcones: a systematic review. Org Biomol Chem 21:5317-5346. https://doi.org/10.1039/D3OB00792H
  34. Karthik V, Lohith TN, Chethan BS et al (2025). Unraveling the synthesis, crystal structure, DFT, pharmacophore, and in silico studies of a chalcone derivative: an experimental and theoretical approaches. Struct Chem, 1-19. https://doi.org/10.1007/s11224-025-02572-w
  35. Adhikari S, Nath P, Deb VK, Das N, Banerjee A, Pathak S, Duttaroy AK (2025) Pharmacological potential of natural chalcones: a recent studies and future perspective. Front Pharma 16:1570385. https://doi.org/10.3389/fphar.2025.1570385
  36. Ngameni B, Cedric K, Mbaveng AT, Erdoğan M, Simo I, Kuete V, Daştan A (2021) Design, synthesis, characterization, and anticancer activity of a novel series of O-substituted chalcone derivatives. Bioorg Med Chem Lett 35:127827. https://doi.org/10.1016/j.bmcl.2021.127827
  37. Rozmer Z, Perjési P (2016) Naturally occurring chalcones and their biological activities. Phytochem Rev, 15:87-120. https://doi.org/10.1007/s11101-014-9387-8
  38. Mujeeb MA, Shahbaz M, Alam MZ, ul Haq Ansari R, Basha HA et al (2025) Recent Advances in the Third Order Nonlinear Optical Properties of Chalcone Derivatives: a Review. J Fluoresc 2025:1-20. https://doi.org/10.1007/s10895-025-04576-5
  39. Otsubo T, Aso Y, Takimiya K (2002) Functional oligothiophenes as advanced molecular electronic materials. J Mat Chem 12:2565-2575. https://doi.org/10.1039/B203780G
  40. Jandial DD, Blair CA, Zhang S, Krill SL et al (2014) Molecular targeted approaches to cancer therapy and prevention using chalcones. Curr Cancer Drug Targets 14:181-200.
  41. Mahapatra, DK, Asati V, Bharti SK (2015) Chalcones and their therapeutic targets for the management of diabetes: Structural and pharmacological perspectives. Eur J Med Chem, 92:839-865. https://doi.org/10.1016/j.ejmech.2015.01.051
  42. Ouyang Y, Li J, Chen X, Fu X, Sun S, Wu Q (2021) Chalcone derivatives: role in anticancer therapy. Biomolecules 11:894. https://doi.org/10.3390/biom11060894
  43. Krajka-Kuźniak V, Belka M, Papierska K (2024) Targeting STAT3 and NF-κB signaling pathways in cancer prevention and treatment: The role of chalcones. Cancers 16:1092. https://doi.org/10.3390/cancers16061092
  44. Catalano A, Mariconda A, D’Amato A, Iacopetta D, Ceramella J, Marra M et al (2024) Aldehydes: what we should know about them. Organics 5:395-428. https://doi.org/10.3390/org5040021
  45. Moloney MG (2024) Reactions of aldehydes and ketones and their derivatives. Org React Mech 2020:1-45. https://doi.org/10.1002/9781119716846.ch1
  46. Rafiee E, Rahimi F (2013) A green approach to the synthesis of chalcones via Claisen-Schmidt condensation reaction using cesium salts of 12-tungstophosphoric acid as a reusable nanocatalyst. Monatsh Chem 144:361-367. https://doi.org/10.1007/s00706-012-0814-5
  47. Silva W A, Nogueira FM, Takada SC (2024) Claisen-Schmidt condensation: an interdisciplinary journey in the organic synthesis laboratory. https://doi.org/10.26434/chemrxiv-2024-l7jcn
  48. Choudhury SS, Mahapatra S, Sahu AK, Hembram P, Jena S, Biswal HS (2022) Synthesis of α, β-Unsaturated Ketones in Water: The Claisen–Schmidt Condensation Revisited. ACS Sust Chem Eng 10:14271-14279. https://doi.org/10.1021/acssuschemeng.2c04388
  49. Dhakshinamoorthy A, Alvaro M, Garcia H (2010) Claisen–Schmidt condensation catalyzed by metal‐organic frameworks. Adv Synth Catal 352:711-717. https://doi.org/10.1002/adsc.200900747
  50. Doraghi F, Kalooei YM, Ghasemi M, Larijani B, Mahdavi M, Al‐Harrasi A (2025) Synthetic Approaches to Chalcone Synthesis. Asian J Org Chem 14:e00099. https://doi.org/10.1002/ajoc.202500099
  51. França SB, Correia PDS, Castro I.D, Júnior ES et al (2021) Synthesis, applications and structure-activity relationship (SAR) of cinnamic acid derivatives: A review. Res. Soc. Dev. 10:e28010111691. http://dx.doi.org/10.33448/rsd-v10i1.11691
  52. Sharma S, Gupta M, Sharma S (2025) Exploring thiophene-based pharmacophores as emerging therapeutics for neurodegenerative disorders. Crit Rev Anal Chem 1-29. https://doi.org/10.1080/10408347.2025.2554239
  53. Constantinescu T, Lungu CN (2021) Anticancer activity of natural and synthetic chalcones. Int J Mol Sci 22: 11306. https://doi.org/10.3390/ijms222111306
  54. Alam MJ, Alam O, Perwez A, Rizvi MA, Naim MJ, Naidu VG et al (2022) Design, synthesis, molecular docking, and biological evaluation of pyrazole hybrid chalcone conjugates as potential anticancer agents and tubulin polymerization inhibitors. Pharmaceuticals 15:280. https://doi.org/10.3390/ph15030280
  55. Jandial DD, Blair AC, Zhang S, Krill SL, Zhang YB, Zi X (2014) Molecular targeted approaches to cancer therapy and prevention using chalcones. Curr Cancer Drug Targets 14:181-200.
  56. Romanelli G, Pasquale G, Sathicq Á, Thomas H, Autino J, Vázquez P (2011) Synthesis of chalcones catalyzed by aminopropylated silica sol–gel under solvent-free conditions. J Mol Cat A: Chem 340:24-32. https://doi.org/10.1016/j.molcata.2011.03.004
  57. Jukic M, Sterk D, Casar Z (2012) Recent advances in the retro-Claisen reaction and its synthetic applications. Curr Org Synth 9:488-512. https://doi.org/10.2174/157017912802651438
  58. Gao F, Huang G, Xiao J (2020) Chalcone hybrids as potential anticancer agents: Current development, mechanism of action, and structure‐activity relationship. Medicinal research reviews 40:2049-2084. https://doi.org/10.1002/med.21698
  59. Moreira J, Loureiro JB, Correia D, Palmeira A, Pinto MM, Saraiva L, Cidade H (2023) Structure–Activity Relationship Studies of Chalcones and Diarylpentanoids with Antitumor Activity: Potency and Selectivity Optimization. Pharmaceuticals 16:1354. https://doi.org/10.3390/ph16101354
  60. Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z (2017) Chalcone: a privileged structure in medicinal chemistry. Chem Rev 117:7762-7810. https://doi.org/10.1021/acs.chemrev.7b00020
  61. Wilhelm A, Bonnet SL, Twigge L, Rarova L, Stenclova T, Visser HG, Schutte-Smith M (2022) Synthesis, characterization and cytotoxic evaluation of chalcone derivatives. J Mol Struct 1251:132001. https://doi.org/10.1016/j.molstruc.2021.132001
  62. Fathi EM, Sroor FM, Mahrous KF, Mohame MF et al (2021) Design, Synthesis, In silico and In Vitro Anticancer Activity of Novel Bis‐Furanyl‐Chalcone Derivatives Linked through Alkyl Spacers. ChemistrySelect 6:6202-6211. https://doi.org/10.1002/slct.202100884
  63. Bueno O, Tobajas G, Quesada E, Estévez-Gallego J, Noppen, S, Camarasa MJ et al (2018) Conformational mimetics of the α-methyl chalcone TUB091 binding tubulin: Design, synthesis and antiproliferative activity. Eur J Med Chem 148:337-348. https://doi.org/10.1016/j.ejmech.2018.02.019
  64. Ducki S, Rennison D, Woo M, Kendall A, Chabert JFD et al (2009) Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity. Bioorg Med Chem 17:7698-7710. https://doi.org/10.1016/j.bmc.2009.09.039
  65. Zhang H, Liu JJ, Sun J, Yang XH, Zhao TT, Lu X et al (2012) Design, synthesis and biological evaluation of novel chalcone derivatives as antitubulin agents. Bioorg Med Chem 20:3212-3218. https://doi.org/10.1016/j.bmc.2012.03.055
  66. Mai C W, Yaeghoobi M, Abd-Rahman N, Kang YB, Pichika MR (2014) Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure–activity relationship analysis and regulation of apoptotic proteins. Eur J Med Chem 77: 378-387. https://doi.org/10.1016/j.ejmech.2014.03.002
  67. Ivković BM, Nikolic K, Ilić BB, Žižak ŽS, Novaković RB, Čudina OA, Vladimirov SM (2013) Phenylpropiophenone derivatives as potential anticancer agents: Synthesis, biological evaluation and quantitative structure–activity relationship study. Eur J Med Chem 63:239-255. https://doi.org/10.1016/j.ejmech.2013.02.013
  68. Wang G, Liu W, Gong Z, Huang Y, Li Y, Peng Z (2020) Synthesis, biological evaluation, and molecular modelling of new naphthalene-chalcone derivatives as potential anticancer agents on MCF-7 breast cancer cells by targeting tubulin colchicine binding site. J Enzyme Inhib Med Chem 35: 139-144. https://doi.org/10.1080/14756366.2019.1690479
  69. Amslinger S (2010) The tunable functionality of α, β‐unsaturated carbonyl compounds enables their differential application in biological systems. ChemMedChem, 5:351-356. https://doi.org/10.1002/cmdc.200900499
  70. Lagu SB, Yejella RP, Bhandare RR, Shaik AB (2020) Design, synthesis, and antibacterial and antifungal activities of novel trifluoromethyl and trifluoromethoxy-substituted chalcone derivatives. Pharmaceuticals 13: 375. https://doi.org/10.3390/ph13110375
  71. Yadav VR., Prasad S, Sung B, Aggarwal BB (2011) The role of chalcones in suppression of NF-κB-mediated inflammation and cancer. Int Immunopharmacol 11:295-309. https://doi.org/10.1016/j.intimp.2010.12.006
  72. Winter E, Locatelli C, Pietro AD, Creczynski-Pasa BT (2015) Recent trends of chalcones potentialities as antiproliferative and antiresistance agents. Anti-Cancer Agents Med Chem 15:592-604. https://doi.org/10.2174/1871520615666150101130800
  73. JR D, Elia, DW, Beazely MA, Kandepu NM (1999) Bioactivities of chalcones. Curr Med Chem 6:1125.
  74. Maydt D, De Spirt S, Muschelknautz C, Stahl W, Müller TJ (2013) Chemical reactivity and biological activity of chalcones and other α, β-unsaturated carbonyl compounds. Xenobiotica 43:711-718. https://doi.org/10.3109/00498254.2012.754112
  75. Nivedya T, Roy N, Paira P, Chakrabarty R (2025) Excavating medicinal virtues of chalcones to illuminate a new scope in cancer chemotherapy. RSC advances 15:11617-11638. https://doi.org/10.1039/d5ra01280e
  76. Ducki S (2009) Antimitotic chalcones and related compounds as inhibitors of tubulin assembly. Anti-Cancer Agents Med Chem 9:336-347. https://doi.org/10.2174/187152009787549223
  77. Dyrager C, Wickström M, Friden-Saxin M, Friberg A et al (2011) Inhibitors and promoters of tubulin polymerization: Synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents. Bioorg Med Chem 19: 2659-2665. https://doi.org/10.1016/j.bmc.2011.03.005
  78. Al-Anazi M, Khairuddean M, Al-Najjar BO, Alidmat MM et al (2021) EGFR Inhibitors and apoptosis inducers: design, docking, synthesis, and anticancer activity of novel tri-chalcone derivatives. Systematic Reviews in Pharmacy 12:809-820.
  79. Ahmed MF, Santali EY, El-Haggar R (2021) Novel piperazine–chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation. J Enzyme Inhib Med Chem 36:308-319. https://doi.org/10.1080/14756366.2020.1861606
  80. Michalkova R, Kello M, Kudlickova Z, Gazdova M et al (2022) Programmed cell death alterations mediated by synthetic indole chalcone resulted in cell cycle arrest, dna damage, apoptosis and signaling pathway modulations in breast cancer model. Pharmaceutics 14:503. https://doi.org/10.3390/pharmaceutics14030503
  81. Wang H, Zhu J, Zhang Q, Tang J, Huang X (2024) Current scenario of chalcone hybrids with antibreast cancer therapeutic applications. Arch Pharm 357:2300640. https://doi.org/10.1002/ardp.202300640
  82. Lin E, Lin WH, Wang SY, Chen CS et al (2012) Flavokawain B inhibits growth of human squamous carcinoma cells: Involvement of apoptosis and cell cycle dysregulation in vitro and in vivo. J Nutr Biochem 23:368-378. https://doi.org/10.1016/j.jnutbio.2011.01.002
  83. Mirossay L, Varinská L, Mojžiš J (2017) Antiangiogenic effect of flavonoids and chalcones: An update. Int J Mol Sci 19: 27. https://doi.org/10.3390/ijms19010027
  84. Moon DO, Choi YH, Moon SK, Kim WJ, Kim GY (2010) Butein suppresses the expression of nuclear factor-kappa B-mediated matrix metalloproteinase-9 and vascular endothelial growth factor in prostate cancer cells. Toxicol in Vitro 24:1927-1934. https://doi.org/10.1016/j.tiv.2010.08.002
  85. Albini A, Dell'Eva R, Vené R, Ferrari N et al (2006) Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF‐κB and Akt as targets. FASEB J 20:527-529. https://doi.org/10.1096/fj.05-5128fje
  86. Wong VKW, Zhang MM, Zhou H, Lam KYC, Chan PL et al (2013) Saikosaponin‐d Enhances the Anticancer Potency of TNF‐α via Overcoming Its Undesirable Response of Activating NF‐Kappa B Signalling in Cancer Cells. Evid Based Complement Alternat Med 2013:745295. https://doi.org/10.1155/2013/745295
  87. Sharma R, Kumar R, Kodwani R, Kapoor S et al (2016) A review on mechanisms of anti tumor activity of chalcones. Anti-Cancer Agents Med Chem 16:200-211.
  88. Song NR, Kim JE, Park JS, Kim JR, Kang H, Lee E et al (2015) Licochalcone A, a polyphenol present in licorice, suppresses UV-induced COX-2 expression by targeting PI3K, MEK1, and B-Raf. Int J Mol Sci 16:4453-4470. https://doi.org/10.3390/ijms16034453
  89. Kamal A, Kashi Reddy M, Viswanath A (2013) The design and development of imidazothiazole–chalcone derivatives as potential anticancer drugs. Expert Opin Drug Discov 8:289-304. https://doi.org/10.1517/17460441.2013.758630
  90. Drąg-Zalesińska M, Drąg M, Poręba M, Borska S, Kulbacka J, Saczko J (2017) Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45). Cancer Cell Int 17: 4. https://doi.org/10.1186/s12935-016-0369-3
  91. Mahapatra DK, Bharti SK, Asati V (2017) Chalcone derivatives: anti-inflammatory potential and molecular targets perspectives. Curr Top Med Chem 17:3146-3169. https://doi.org/10.2174/1568026617666170914160446
  92. Gao S, Hu M (2010) Bioavailability challenges associated with development of anti-cancer phenolics. Mini Rev Med Chem 10:550-567. https://doi.org/10.2174/138955710791384081
  93. Kaumanns O, Mayr H (2008) Electrophilicity parameters of 5-benzylidene-2, 2-dimethyl [1, 3] dioxane-4, 6-diones (benzylidene Meldrum's acids). J Org Chem 73:2738-2745. https://doi.org/10.1021/jo702590s
  94. Dhaliwal JS, Moshawih S, Goh KW, Loy MJ et al (2022) Pharmacotherapeutics applications and chemistry of chalcone derivatives. Molecules 27:7062. https://doi.org/10.3390/molecules27207062
  95. Moreira J, Almeida J, Saraiva L, Cidade H, Pinto M (2021) Chalcones as promising antitumor agents by targeting the p53 pathway: An overview and new insights in drug-likeness. Molecules 26:3737. https://doi.org/10.3390/molecules26123737
  96. Manaithiya A, Bhowmik R, Acharjee S, Sharma S, Kumar S et al (2024) Elucidating Molecular Mechanism and Chemical Space of Chalcones through Knowledge Graph and Machine Learning: A Combined Bio-Cheminformatic Pipeline. BioRxiv 2024:592581. https://doi.org/10.1101/2024.05.05.592581
  97. Li M, Zhang C, Liang H, Wu B, Yu Wet al (2025) Machine learning-guided engineering of chalcone synthase enables high-selectivity phloretin biosynthesis in yeast. Green Chem 27:12602-12612. https://doi.org/10.1039/D5GC03435C
  98. World Health Organization. "Cancer". https://gco.iarc.fr/tomorrow/en/dataviz/isotype, Accessed 18 August 2024.