SpringerLink
Log in

Targeting growth of breast cancer cell line (MCF-7) with curcumin-pyrimidine analogs

  • Rapid Communication
  • Published:
Journal of Chemical Sciences Aims and scope Submit manuscript

Abstract

A series of curcumin-pyrimidine analogs (3a-3h) were synthesized with good yields using phase transfer catalysis. The antiproliferative activities of the synthesized compounds were examined against two human breast cancer cell lines, MCF-7 and MDA-MB-231. Compounds 3b and 3g demonstrated potent antiproliferative activity against MCF-7 cancer cell lines with an IC50 value of 4.95 ± 0.94 µM and 0.61 ± 0.05 µM respectively. Compounds 3b and 3g displayed significantly less cytotoxicity towards non-tumorigenic MCF-10A cells. Further, 3b and 3g were investigated for cell cycle analysis and colony formation assays. Flow cytometry showed cell cycle arrest and induced apoptosis in dose and time-dependent manner. In colony formation assay, 3b and 3g caused a significant decrease in the number of colonies in MCF-7 cell line. Molecular docking studies against human epidermal growth factor receptor 2 (HER2) (PDB ID:3PP0), estrogen receptor (PDB ID: 3ERT), and progesterone receptor (PDB ID: 3G8O) showed strong binding interactions.

Graphical Abstract

Curcumin-pyrimidine analogs are synthesized and screened against MCF-7 and MDA-MB-231 cancer cell lines. Two analogs showed higher in vitro antiproliferative activities against MCF-7 with IC50 values of 4.95 and 0.61 µM. These compounds induce apoptosis in cycle analyses, inhibit colony formation, and show good binding interactions in molecular docking studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Scheme 1
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10

References

  1. Jakubczyk K, Drużga A, Katarzyna J and Skonieczna-żydecka K 2020 Antioxidant potential of curcumin—a meta-analysis of randomized clinical trials Antioxidants 9 1

  2. Alabdali A, Kzar M, Chinnappan S, Mogana R, Khalivulla SI, Rahman H and AbdRazik B M 2021 Antioxidant activity of curcumin Res. J. Pharm. Technol. 14 6741

    Article  Google Scholar 

  3. Teow S Y, Liew K, Ali S A, Khoo A S B and Peh S C 2016 Antibacterial action of curcumin against Staphylococcus aureus: A Brief Review J. Trop. Med. 2016

  4. Zheng D, Huang C, Huang H, Zhao Y, Khan M R U, Zhao H and Huang L 2020 Antibacterial mechanism of curcumin: A review Chem. Biodivers. 17 1

    Article  Google Scholar 

  5. Zorofchian Moghadamtousi S, Abdul Kadir H, Hassandarvish P, Tajik H, Abubakar S and Zandi K 2014 A review on antibacterial, antiviral, and antifungal activity of curcumin Biomed. Res. Int. 2014

  6. Jennings M R and Parks R J 2020 Curcumin as an antiviral agent Viruses 12 1242

    Article  CAS  Google Scholar 

  7. Marton L T, Pescinini-e-Salzedas L M, Camargo M E C, Barbalho S M, Haber J F dos S, Sinatora R V, Detregiachi C R P, Girio R J S, Buchaim D V and Cincotto dos Santos Bueno P 2021 The effects of curcumin on diabetes mellitus: A systematic review Front. Endocrinol. (Lausanne) 12

  8. FazelNabavi S, Thiagarajan R, Rastrelli L, Daglia M, Sobarzo-Sanchez E, Alinezhad H and Mohammad Nabavi S 2015 Curcumin: a natural product for diabetes and its complications Curr. Top Med. Chem. 15 2445

    Article  Google Scholar 

  9. Fadus M C, Lau C, Bikhchandani J and Lynch H T 2017 Curcumin: An age-old anti-inflammatory and anti-neoplastic agent J. Tradit. Comp. Med. 7 339

    Article  Google Scholar 

  10. Peng Y, Ao M, Dong B, Jiang Y, Yu L, Chen Z, et al. 2021 Anti-inflammatory effects of curcumin in the inflammatory diseases: Status, limitations and countermeasures Drug Des. Devel. Ther. 15 4503

    Article  CAS  Google Scholar 

  11. Pongrakhananon V, Rojanasakul Y 2011 Anticancer Properties of Curcumin. In: Gali-Muhtasib, H (Ed.) Advances in Cancer Therapy (London: IntechOpen)

  12. Tomeh M A, Hadianamrei R and Zhao X 2019 A review of curcumin and its derivatives as anticancer agents Int. J. Mol. Sci. 20 1033

  13. Wilken R, Veena M S, Wang M B and Srivatsan E S 2011 Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma Mol. Cancer 10

  14. Koohpar Z K, Entezari M, Movafagh A and Hashemi M 2015 Anticancer activity of curcumin on human breast adenocarcinoma: Role of Mcl-1 gene Int. J. Cancer Manag. 8

  15. De A, Beligala D H, Birkholz T M and Geusz M E 2019 Anticancer properties of curcumin and interactions with the circadian timing system Integr. Cancer Ther. 18

  16. Rahmani A H, al Zohairy M A, Aly S M and Khan M A 2014 Curcumin: A potential candidate in prevention of cancer via modulation of molecular pathways Biomed. Res. Int. 2014

  17. Chandra R, Reddy Danduga S, Kumar Kola P and Matli B 2020 Anticancer activity of curcumin alone and in combination with piperine in Dalton lymphoma ascites bearing mice Indian J. Exp. Biol. 58 181

    Google Scholar 

  18. Pongrakhananon V and Rojanasakul Y 2011 Anticancer Properties of Curcumin In: Advances in Cancer Therapy [Internet] H H Gali-Muhtasib (Ed.) (London: IntechOpen)

  19. Shaikh S, Shaikh J, Naba Y S, Doke K, Ahmed K and Yusufi M 2021 Curcumin: Reclaiming the lost ground against cancer resistance Cancer Drug Resist. 4 298

  20. Hatamipour M, Hadizadeh F, Jaafari M R, Khashyarmanesh Z, Sathyapalan T and Sahebkar A 2022 Antiproliferative potential of fluorinated curcumin analogues: experimental and computational analysis and review of the literature Curr. Med. Chem. 29 1459

    Article  CAS  Google Scholar 

  21. Gupta T, Singh J, Kaur S, Sandhu S, Singh G and Kaur I P 2020 Enhancing bioavailability and stability of curcumin using solid lipid nanoparticles (CLEN): a covenant for its effectiveness Front. Bioeng. Biotechnol. 8

  22. Liu W, Zhai Y, Heng X, Che F Y, Chen W, Sun D and Zhai G 2016 Oral bioavailability of curcumin: problems and advancements J. Drug Target 24 694

    Article  CAS  Google Scholar 

  23. Rodrigues F C, Kumar N A and Thakur G 2021 The potency of heterocyclic curcumin analogues: An evidence-based review Pharmacol. Res. 166

  24. Martinez-Cifuentes M, Weiss-Lopez B, S Santos L and Araya-Maturana R 2015 Heterocyclic curcumin derivatives of pharmacological interest: Recent progress Curr. Top Med. Chem. 15 1663

  25. Shaikh S B, Mulani S, Tambat N, Shaikh I, Ahmad A and Ahmed K 2022 1, 3-diketo curcumin scaffolds: A gateway to profuse bioactive heterocycles Annal. Phytomed. Int. J. 11 175

    CAS  Google Scholar 

  26. Tambat N, Mulani S K, Ahmad A, Shaikh S B and Ahmed K 2022 Pyrazine derivatives—Versatile scaffold Russ. J. Bioorg. Chem. 48 865

    Article  CAS  Google Scholar 

  27. JeelanBasha N, Basavarajaiah S M and Shyamsunder K 2022 Therapeutic potential of pyrrole and pyrrolidine analogs: an update Mol. Divers. 26 2915

    Article  CAS  Google Scholar 

  28. Albratty M and Alhazmi H A 2022 Novel pyridine and pyrimidine derivatives as promising anticancer agents: A review Arab. J. Chem. 15 103846

    Article  CAS  Google Scholar 

  29. Bahmani A, Najafi Z and Chehardoli G 2022 Curcumin-derived heterocycles as anticancer agents. A systematic review Org. Prep. Proced. Int. 8 1

  30. Nabil S, El-Rahman S N A, Al-Jameel SS and Elsharif A M 2018 Conversion of curcumin into heterocyclic compounds as potent anti-diabetic and anti-histamine agents Biol. Pharm. Bull. 41 1071

    Article  CAS  Google Scholar 

  31. Dai X, Cheng H, Bai Z and Li J 2017 Breast cancer cell line classification and its relevance with breast tumor subty** J. Cancer 8 3131

    Article  Google Scholar 

  32. Jarman E J, Ward C, Turnbull A K, Martinez-Perez C, Meehan J, **ntaropoulou C, Sims A H and Langdon S P 2019 HER2 regulates HIF-2α and drives an increased hypoxic response in breast cancer Breast Cancer Res. 21 10

  33. Jenie R I, Handayani S, Susidarti R A, Udin L Z and Meiyanto E 2018 The cytotoxic and antimigratory activity of brazilin-doxorubicin on MCF-7/HER2 Cells Adv. Pharm. Bull. 8 507

    Article  CAS  Google Scholar 

  34. Pablos J L, Estévez P, Muñoz A, Ibeas S, Serna F, García F C and García J M 2015 Polymer chemosensors as solid films and coated fibres for extreme acidity colorimetric sensing J. Mater. Chem. A Mater. 3 2833

    Article  CAS  Google Scholar 

  35. van Meerloo J, Kaspers G J and Cloos J 2011 Cell sensitivity assays: the MTT assay Methods Mol. Biol. 731 237

  36. Franken N A P, Rodermond H M, Stap J, Haveman J and van Bree C 2006 Clonogenic assay of cells in vitro Nat. Protoc. 1 2315

    Article  CAS  Google Scholar 

  37. Morris G M, Huey R, Lindstrom W, Sanner M F, Belew R K, Goodsell D S and Olson A J 2009 AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility J. Comput. Chem. 30 2785

    Article  CAS  Google Scholar 

  38. Mohan P R K, Sreelakshmi G, Muraleedharan C V and Joseph R 2012 Water soluble complexes of curcumin with cyclodextrins: Characterization by FT-Raman spectroscopy Vib. Spectrosc. 62 77

    Article  CAS  Google Scholar 

  39. Gupta E, Kaushik S, Purwar S, Sharma R, Balapure A and Sundaram S 2017 Anticancer potential of steviol in MCF-7 human breast cancer cells Pharmacogn. Mag. 13 345

    Article  CAS  Google Scholar 

  40. Singh N, Nigam M, Ranjan V, Sharma R, Balapure A K and Rath S K 2009 Caspase mediated enhanced apoptotic action of cyclophosphamide- and resveratrol-treated MCF-7 cells J. Pharmacol. Sci. 109 473

    Article  CAS  Google Scholar 

  41. Ramadoss D and Sivalingam N 2021 Vanillin extracted from proso and barnyard millets induces cell cycle inhibition and apoptotic cell death in MCF-7 cell line J. Cancer Res. Ther. 17 1425

    Article  CAS  Google Scholar 

  42. Ali N M, Yeap S K, Abu N, Lim K L, Ky H, Pauzi A Z M, Ho W Y, Tan S W, Alan-Ong H K, Zareen S, Alitheen N B and Akhtar M N 2017 Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells Cancer Cell Int. 17 30

  43. Mohd Ali N, Akhtar N M, Ky H, Lim K L, Abu N, Zareen S, Wan Yong H, Alan-Ong H, Tan S W, Mohamed Alitheen N B, Ismail J, Swee Keong Y and Kamarul T 2016 Flavokawain derivative FLS induced G2/M arrest and apoptosis on breast cancer MCF-7 cell line Drug Des. Devel. Ther. 1897

  44. Luo B, Wu X-H, Feng Y-J, Zheng H-M, Zhang Q, Liang X-J, Huang D-F and Xu J 2021 Nuclear HER2 contributes to paclitaxel resistance in breast cancer cells Anticancer Drugs 32 709

  45. Krishnamurti U and Silverman J F 2014 HER2 in breast cancer: a review and update Adv. Anat. Pathol. 21 100

    Article  CAS  Google Scholar 

  46. Qin J, Qu S, Zhu K, Cheng Y, Pan G, **g W, et al. 2021 Rational design and synthesis of 6-aryl-6H-benzo[c]chromenes as non-steroidal progesterone receptor antagonists for use against cancers Bioorg. Med. Chem. 32 116003

    Article  CAS  Google Scholar 

  47. Barone I, Brusco L and Fuqua S A W 2010 Estrogen receptor mutations and changes in downstream gene expression and signaling Clinic. Cancer Res. 16 2702

    Article  CAS  Google Scholar 

  48. Ranjan A P, Mukerjee A, Gdowski A, Helson L, Bouchard A, Majeed M and Vishwanatha J K 2016 Curcumin-ER prolonged subcutaneous delivery for the treatment of non-small cell lung cancer J. Biomed. Nanotechnol. 12 679

    Article  CAS  Google Scholar 

  49. MohdFisall U F, Ismail N Z, Adebayo I A and Arsad H 2021 Dichloromethane fraction of Moringa oleifera leaf methanolic extract selectively inhibits breast cancer cells (MCF7) by induction of apoptosis via upregulation of Bax, p53 and caspase 8 expressions Mol. Biol. Rep. 48 4465

    Article  CAS  Google Scholar 

  50. Raeisi F, Raeisi E, Heidarian E, Shahbazi-Gahroui D and Lemoigne Y 2019 Bromelain inhibitory effect on colony formation: An In vitro Study on human AGS, PC3, and MCF7 cancer cells J. Med. Signals Sens. 9 267

    Article  Google Scholar 

Download references

Acknowledgements

We are thankful to the Department of Science and Technology, Govt. of India, for providing financial assistance under DST-FIST (0 Level) to Abeda Inamdar Senior College, Pune vide letter number SR/FST/COLLEGE-277/2018 dated 20th December 2018. We are grateful to Dr. P. A. Inamdar, the President of MCE Society, Pune, for providing the laboratory facilities. This work was supported by the BCUD, Savitribai Phule Pune University, Pune- 07. (Proposal no. 15SCI001417). We are also thankful to Amit S. Salunkhe and Ashwini Kore, FACS Department, NCCS, Pune, for FACS analysis and data.

Author information

Authors and Affiliations

  1. Advanced Scientific Research Laboratory, Department of Chemistry, MCE Society’s Abeda Inamdar Senior College of Arts, Science and Commerce, Azam Campus, Pune, 411001, India

    Siraj B Shaikh, Pranav Tambe, Yusufi Mujahid & Khursheed Ahmed

  2. National Centre for Cell Science, Pune, 411007, India

    Manas K Santra

  3. Department of Organic Chemistry, University Bayreuth, Universitaetsstr. 30, 95440, Bayreuth, Germany

    Bernhard Biersack

Authors
  1. Siraj B Shaikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pranav Tambe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yusufi Mujahid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manas K Santra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bernhard Biersack
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Khursheed Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Khursheed Ahmed.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 2029 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shaikh, S.B., Tambe, P., Mujahid, Y. et al. Targeting growth of breast cancer cell line (MCF-7) with curcumin-pyrimidine analogs. J Chem Sci 134, 123 (2022). https://doi.org/10.1007/s12039-022-02115-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12039-022-02115-4

Keywords

Search

Navigation